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2. Clinical outcomes in children living with HIV treated for non-severe tuberculosis in the SHINE Trial

Author

Chabala, C, Wobudeya, E, van der Zalm, MM, Kapasa, M, Raichur, P, Mboizi, R, Palmer, M, Kinikar, A, Hissar, S, Mulenga, V, Mave, V, Musoke, P, Hesseling, AC, McIlleron, H, Gibb, D, Crook, A, Turkova, A, SHINE trial team, Chabala, C, Wobudeya, E, van der Zalm, MM, Kapasa, M, Raichur, P, Mboizi, R, Palmer, M, Kinikar, A, Hissar, S, Mulenga, V, Mave, V, Musoke, P, Hesseling, AC, McIlleron, H, Gibb, D, Crook, A, Turkova, A, and SHINE trial team

Abstract

BACKGROUND: Children living with HIV(CLWH) are at high risk of tuberculosis(TB) and face poor outcomes, despite antiretroviral treatment(ART). We evaluated outcomes in CLWH and HIV-uninfected children treated for non-severe TB in the SHINE trial. METHODS: SHINE was a randomized trial that enrolled children aged <16 years with smear-negative, non-severe TB who were randomized to receive 4 vs 6 months of TB treatment and followed for 72 weeks. We assessed TB relapse/recurrence, mortality, hospitalizations, grade ≥3 adverse events by HIV status, and HIV virological suppression in CLWH. RESULTS: Of 1204 enrolled, 127(11%) were CLWH, of similar age (median(IQR) 3.6(1.2, 10.3) vs. 3.5(1.5, 6.9)years, p= 0.07), but more underweight (WAZ; -2.3(-3.3, -0.8) vs -1.0(-1.8, -0.2), p<0.01) and anemic (hemoglobin 9.5(8.7, 10.9) vs 11.5(10.4, 12.3)g/dl, p<0.01) compared to HIV-uninfected children. 68(54%) CLWH were ART-naïve; baseline median CD4 count 719(241-1134) cells/mm3, CD4% 16(10-26)%). CLWH were more likely to be hospitalized (aOR=2.4(1.3-4.6)) and die (aHR(95%CI) 2.6(1.2,5.8)). HIV status, age <3 years (aHR 6.3(1.5,27.3)), malnutrition (aHR 6.2(2.4,15.9)) and hemoglobin <7g/dl(aHR 3.8(1.3,11.5) independently predicted mortality. Among children with available VL, 45% and 61% CLWH had VL<1000copies/ml at weeks 24 and 48, respectively. There was no difference in the effect of randomized treatment duration (4 vs 6 months) on TB treatment outcomes by HIV status (p for interaction=0.42). CONCLUSIONS: We found no evidence of a difference in TB outcomes between 4 and 6 months of treatment for CLWH treated for non-severe TB. Irrespective of TB treatment duration, CLWH had higher rates of mortality and hospitalization than HIV-uninfected counterparts.

Published
2024

3. Oral abstracts of the 21st International AIDS Conference 18–22 July 2016, Durban, South Africa

Author

Ericsen, A, Lauck, M, Mohns, M, Dinapoli, S, Mutschler, J, Greene, J, Weinfurter, J, Lehrer‐Brey, G, Crosno, K, Peterson, E, Reynolds, M, Wiseman, R, Burwitz, B, Sacha, J, Friedrich, T, Brenchley, J, O'Connor, D, Xu, C, He, T, Haret‐Richter, G, Franck, D, Policicchio, B, Brocca‐Cofano, E, Ma, D, Stock, J, Tracy, R, Landay, A, Wilson, C, Apetrei, C, Pandrea, I, Wong, EB, Xulu, B, Prakadan, S, Shalek, AK, Lalloo, U, Baijnath, P, Suleman, M, Moodley, V, Mitha, M, Maharaj, P, Costiniuk, C, Nielsen, M, Mhlane, Z, Karim, F, Lewinsohn, D, Ndung'u, T, Pasternak, A, Prins, J, Berkhout, B, Leon‐Fuentes, L, Viveros‐Rogel, M, Vergara‐Mendoza, M, Rodriguez‐Castañón, M, Cardenas‐Ochoa, A, Tello‐Mercado, A, Vega, C, Sierra‐Madero, J, Soto‐Ramirez, L, Perez‐Patrigeon, S, Hensley‐Mcbain, T, Cheu, R, Manuzak, J, Zevin, A, Miller, C, Lee, E, Burgener, A, Klatt, N, Mellins, CA, Abrams, EJ, Dolezal, C, Warne, P, Elkington, K, Bucek, A, Leu, CS, Maskew, M, Bor, J, MacLeod, W, Carmona, S, Sherman, G, Fox, MP, Judd, A, Chappell, E, Doerholt, K, Galli, L, Giaquinto, C, Gibb, D, Goetghebuer, T, Le Coeur, S, Julian, A Noguera, Turkova, A, Goodall, R, Collaboration, European Pregnancy and Paediatric Hiv Cohort, Davies, M‐A, Sawry, S, Phiri, S, Rabie, H, Eley, B, Fatti, G, and Technau, K‐G

Subjects
Mental Health, Pediatric AIDS, Pediatric, Infectious Diseases, Prevention, Digestive Diseases, Pediatric Research Initiative, Clinical Research, Bioengineering, HIV/AIDS, Basic Behavioral and Social Science, Health Services, Behavioral and Social Science, Infection, Reproductive health and childbirth, Good Health and Well Being, Clinical Sciences, Public Health and Health Services, Other Medical and Health Sciences
Published
2016

7. Global estimates and determinants of antituberculosis drug pharmacokinetics in children and adolescents: a systematic review and individual patient data meta-analysis.

Author

Gafar, F., Wasmann, R.E., McIlleron, H.M., Aarnoutse, R.E., Schaaf, H.S., Marais, B.J., Agarwal, D., Antwi, S., Bang, N.D., Bekker, A., Bell, D.J., Chabala, C., Choo, L., Davies, G.R., Day, J.N., Dayal, R., Denti, P., Donald, P.R., Engidawork, E., Garcia-Prats, A.J., Gibb, D., Graham, S.M., Hesseling, A.C., Heysell, S.K., Idris, M.I., Kabra, S.K., Kinikar, A., Kumar, A.K.H., Kwara, A., Lodha, R., Magis-Escurra, C., Martinez, N., Mathew, B.S., Mave, V., Mduma, E., Mlotha-Mitole, R., Mpagama, S.G., Mukherjee, A., Nataprawira, H.M., Peloquin, C.A., Pouplin, T., Ramachandran, G., Ranjalkar, J., Roy, V., Ruslami, Rovina, Shah, I., Singh, Y., Sturkenboom, M.G., Svensson, E.M., Swaminathan, S., Thatte, U., Thee, S., Thomas, T.A., Tikiso, T., Touw, D.J., Turkova, A., Velpandian, T., Verhagen, L.M., Winckler, J.L., Yang, H., Yunivita, V., Taxis, K., Stevens, J., Alffenaar, J.C., Gafar, F., Wasmann, R.E., McIlleron, H.M., Aarnoutse, R.E., Schaaf, H.S., Marais, B.J., Agarwal, D., Antwi, S., Bang, N.D., Bekker, A., Bell, D.J., Chabala, C., Choo, L., Davies, G.R., Day, J.N., Dayal, R., Denti, P., Donald, P.R., Engidawork, E., Garcia-Prats, A.J., Gibb, D., Graham, S.M., Hesseling, A.C., Heysell, S.K., Idris, M.I., Kabra, S.K., Kinikar, A., Kumar, A.K.H., Kwara, A., Lodha, R., Magis-Escurra, C., Martinez, N., Mathew, B.S., Mave, V., Mduma, E., Mlotha-Mitole, R., Mpagama, S.G., Mukherjee, A., Nataprawira, H.M., Peloquin, C.A., Pouplin, T., Ramachandran, G., Ranjalkar, J., Roy, V., Ruslami, Rovina, Shah, I., Singh, Y., Sturkenboom, M.G., Svensson, E.M., Swaminathan, S., Thatte, U., Thee, S., Thomas, T.A., Tikiso, T., Touw, D.J., Turkova, A., Velpandian, T., Verhagen, L.M., Winckler, J.L., Yang, H., Yunivita, V., Taxis, K., Stevens, J., and Alffenaar, J.C.

Abstract

Item does not contain fulltext, BACKGROUND: Suboptimal exposure to antituberculosis (anti-TB) drugs has been associated with unfavourable treatment outcomes. We aimed to investigate estimates and determinants of first-line anti-TB drug pharmacokinetics in children and adolescents at a global level. METHODS: We systematically searched MEDLINE, Embase and Web of Science (1990-2021) for pharmacokinetic studies of first-line anti-TB drugs in children and adolescents. Individual patient data were obtained from authors of eligible studies. Summary estimates of total/extrapolated area under the plasma concentration-time curve from 0 to 24 h post-dose (AUC(0-24)) and peak plasma concentration (C (max)) were assessed with random-effects models, normalised with current World Health Organization-recommended paediatric doses. Determinants of AUC(0-24) and C (max) were assessed with linear mixed-effects models. RESULTS: Of 55 eligible studies, individual patient data were available for 39 (71%), including 1628 participants from 12 countries. Geometric means of steady-state AUC(0-24) were summarised for isoniazid (18.7 (95% CI 15.5-22.6) h·mg·L(-1)), rifampicin (34.4 (95% CI 29.4-40.3) h·mg·L(-1)), pyrazinamide (375.0 (95% CI 339.9-413.7) h·mg·L(-1)) and ethambutol (8.0 (95% CI 6.4-10.0) h·mg·L(-1)). Our multivariate models indicated that younger age (especially <2 years) and HIV-positive status were associated with lower AUC(0-24) for all first-line anti-TB drugs, while severe malnutrition was associated with lower AUC(0-24) for isoniazid and pyrazinamide. N-acetyltransferase 2 rapid acetylators had lower isoniazid AUC(0-24) and slow acetylators had higher isoniazid AUC(0-24) than intermediate acetylators. Determinants of C (max) were generally similar to those for AUC(0-24). CONCLUSIONS: This study provides the most comprehensive estimates of plasma exposures to first-line anti-TB drugs in children and adolescents. Key determinants of drug exposures were identified. These may be relevant for population-specif

Published
2023

8. Evaluating pediatric tuberculosis dosing guidelines: A model-based individual data pooled analysis.

Author

Galileya, L.T., Wasmann, R.E., Chabala, C., Rabie, H., Lee, J., Njahira Mukui, I., Hesseling, A., Zar, H., Aarnoutse, R.E., Turkova, A., Gibb, D., Cotton, M.F., McIlleron, H., Denti, P., Galileya, L.T., Wasmann, R.E., Chabala, C., Rabie, H., Lee, J., Njahira Mukui, I., Hesseling, A., Zar, H., Aarnoutse, R.E., Turkova, A., Gibb, D., Cotton, M.F., McIlleron, H., and Denti, P.

Abstract

Contains fulltext : 300019.pdf (Publisher’s version ) (Open Access), BACKGROUND: The current World Health Organization (WHO) pediatric tuberculosis dosing guidelines lead to suboptimal drug exposures. Identifying factors altering the exposure of these drugs in children is essential for dose optimization. Pediatric pharmacokinetic studies are usually small, leading to high variability and uncertainty in pharmacokinetic results between studies. We pooled data from large pharmacokinetic studies to identify key covariates influencing drug exposure to optimize tuberculosis dosing in children. METHODS AND FINDINGS: We used nonlinear mixed-effects modeling to characterize the pharmacokinetics of rifampicin, isoniazid, and pyrazinamide, and investigated the association of human immunodeficiency virus (HIV), antiretroviral therapy (ART), drug formulation, age, and body size with their pharmacokinetics. Data from 387 children from South Africa, Zambia, Malawi, and India were available for analysis; 47% were female and 39% living with HIV (95% on ART). Median (range) age was 2.2 (0.2 to 15.0) years and weight 10.9 (3.2 to 59.3) kg. Body size (allometry) was used to scale clearance and volume of distribution of all 3 drugs. Age affected the bioavailability of rifampicin and isoniazid; at birth, children had 48.9% (95% confidence interval (CI) [36.0%, 61.8%]; p < 0.001) and 64.5% (95% CI [52.1%, 78.9%]; p < 0.001) of adult rifampicin and isoniazid bioavailability, respectively, and reached full adult bioavailability after 2 years of age for both drugs. Age also affected the clearance of all drugs (maturation), children reached 50% adult drug clearing capacity at around 3 months after birth and neared full maturation around 3 years of age. While HIV per se did not affect the pharmacokinetics of first-line tuberculosis drugs, rifampicin clearance was 22% lower (95% CI [13%, 28%]; p < 0.001) and pyrazinamide clearance was 49% higher (95% CI [39%, 57%]; p < 0.001) in children on lopinavir/ritonavir; isoniazid bioavailability was reduced by 39% (95% C, 01 november 2023

Published
2023

9. Inadequate Lopinavir Concentrations With Modified 8-Hourly Lopinavir/Ritonavir 4:1 Dosing During Rifampicin-based Tuberculosis Treatment in Children Living With HIV

Author

Chabala, C., Turkova, A., Kapasa, M., LeBeau, K., Tembo, C.H., Zimba, K., Weisner, L., Zyambo, K., Choo, L., Chungu, C., Lungu, J., Mulenga, V., Crook, A., Aarnoutse, R.E., Gibb, D., McIlleron, H., Chabala, C., Turkova, A., Kapasa, M., LeBeau, K., Tembo, C.H., Zimba, K., Weisner, L., Zyambo, K., Choo, L., Chungu, C., Lungu, J., Mulenga, V., Crook, A., Aarnoutse, R.E., Gibb, D., and McIlleron, H.

Abstract

Item does not contain fulltext, BACKGROUND: Lopinavir/ritonavir plasma concentrations are profoundly reduced when co-administered with rifampicin. Super-boosting of lopinavir/ritonavir is limited by nonavailability of single-entity ritonavir, while double-dosing of co-formulated lopinavir/ritonavir given twice-daily produces suboptimal lopinavir concentrations in young children. We evaluated whether increased daily dosing with modified 8-hourly lopinavir/ritonavir 4:1 would maintain therapeutic plasma concentrations of lopinavir in children living with HIV receiving rifampicin-based antituberculosis treatment. METHODS: Children with HIV/tuberculosis coinfection weighing 3.0 to 19.9 kg, on rifampicin-based antituberculosis treatment were commenced or switched to 8-hourly liquid lopinavir/ritonavir 4:1 with increased daily dosing using weight-band dosing approach. A standard twice-daily dosing of lopinavir/ritonavir was resumed 2 weeks after completing antituberculosis treatment. Plasma sampling was conducted during and 4 weeks after completing antituberculosis treatment. RESULTS: Of 20 children enrolled; 15, 1-7 years old, had pharmacokinetics sampling available for analysis. Lopinavir concentrations (median [range]) on 8-hourly lopinavir/ritonavir co-administered with rifampicin (n = 15; area under the curve 0-24 55.32 mg/h/L [0.30-398.7 mg/h/L]; C max 3.04 mg/L [0.03-18.6 mg/L]; C 8hr 0.90 mg/L [0.01-13.7 mg/L]) were lower than on standard dosing without rifampicin (n = 12; area under the curve 24 121.63 mg/h/L [2.56-487.3 mg/h/L]; C max 9.45 mg/L [0.39-26.4 mg/L]; C 12hr 3.03 mg/L [0.01-17.7 mg/L]). During and after rifampicin cotreatment, only 7 of 15 (44.7%) and 8 of 12 (66.7%) children, respectively, achieved targeted pre-dose lopinavir concentrations ≥1mg/L. CONCLUSIONS: Modified 8-hourly dosing of lopinavir/ritonavir failed to achieve adequate lopinavir concentrations with concurrent antituberculosis treatment. The subtherapeutic lopinavir exposures on standard dosing after antituberculosis

Published
2023

10. Pharmacokinetics and pharmacodynamics of azithromycin in severe malaria bacterial co-infection in African children (TABS-PKPD): a protocol for a Phase II randomised controlled trial [version 2; peer review: 1 approved]

Author

Olupot-Olupot, P, Okiror, W, Mnjalla, H, Muhindo, R, Uyoga, S, Mpoya, A, Williams, T, TerHeine, R, Burger, D, Urban, B, Connon, R, George, E, Gibb, D, Walker, S, and Maitland, K

Abstract

Background: African children with severe malaria are susceptible to Gram-negative bacterial co-infection, largely non-typhoidal Salmonellae, leading to a substantially higher rates of in-hospital and post-discharge mortality than those without bacteraemia. Current evidence for treating co-infection is lacking, and there is no consensus on the dosage or length of treatment required. We therefore aimed to establish the appropriate dose of oral dispersible azithromycin as an antimicrobial treatment for children with severe malaria and to investigate whether antibiotics can be targeted to those at greatest risk of bacterial co-infection using clinical criteria alone or in combination with rapid diagnostic biomarker tests. Methods: A Phase I/II open-label trial comparing three doses of azithromycin: 10, 15 and 20 mg/kg spanning the lowest to highest mg/kg doses previously demonstrated to be equally effective as parenteral treatment for other salmonellae infection. Children with the highest risk of bacterial infection will receive five days of azithromycin and followed for 90 days. We will generate relevant pharmacokinetic data by sparse sampling during dosing intervals. We will use population pharmacokinetic modelling to determine the optimal azithromycin dose in severe malaria and investigate azithromycin exposure to change in C-reactive protein, a putative marker of sepsis at 72 hours, and microbiological cure (seven-day), alone and as a composite with seven-day survival. We will also evaluate whether a combination of clinical, point-of-care diagnostic tests, and/or biomarkers can accurately identify the sub-group of severe malaria with culture-proven bacteraemia by comparison with a control cohort of children hospitalized with severe malaria at low risk of bacterial co-infection. Discussion: We plan to study azithromycin because of its favourable microbiological spectrum, its inherent antimalarial and immunomodulatory properties and dosing and safety profile. This study will generate new data to inform the design and sample size for definitive Phase III trial evaluation. Registration: ISRCTN49726849 (27th October 2017).

Published
2023

12. The cost‐effectiveness of prophylaxis strategies for individuals with advanced HIV starting treatment in Africa

Author

Walker, Simon M., Cox, Edward, Revill, Paul, Musiime, Victor, Bwakura?Dangarembizi, Mutsa, Mallewa, Jane, Cheruiyot, Priscilla, Maitland, Kathryn, Ford, Nathan, Gibb, Diana M., Walker, A Sarah, Soares, Marta, Mugyenyi, P, Kityo, C, Musiime, V, Wavamunno, P, Nambi, E, Ocitti, P, Ndigendawani, M, Kabahenda, S, Kemigisa, M, Acen, J, Olebo, D, Mpamize, G, Amone, A, Okweny, D, Mbonye, A, Nambaziira, F, Rweyora, A, Kangah, M, Kabaswahili, V, Abach, J, Abongomera, G, Omongin, J, Aciro, I, Philliam, A, Arach, B, Ocung, E, Amone, G, Miles, P, Adong, C, Tumsuiime, C, Kidega, P, Otto, B, Apio, F, Baleeta, K, Mukuye, A, Abwola, M, Ssennono, F, Baliruno, D, Tuhirwe, S, Namisi, R, Kigongo, F, Kikyonkyo, D, Mushahara, F, Tusiime, J, Musiime, A, Nankya, A, Atwongyeire, D, Sirikye, S, Mula, S, Noowe, N, Lugemwa, A, Kasozi, M, Mwebe, S, Atwine, L, Senkindu, T, Natuhurira, T, Katemba, C, Ninsiima, E, Acaku, M, Kyomuhangi, J, Ankunda, R, Tukwasibwe, D, Ayesiga, L, Hakim, J, Nathoo, K, Bwakura?Dangarembizi, M, Reid, A, Chidziva, E, Mhute, T, Tinago, Gc, Bhiri, J, Mudzingwa, S, Phiri, M, Steamer, J, Nhema, R, Warambwa, C, Musoro, G, Mutsai, S, Nemasango, B, Moyo, C, Chitongo, S, Rashirai, K, Vhembo, S, Mlambo, B, Nkomani, S, Ndemera, B, Willard, M, Berejena, C, Musodza, Y, Matiza, P, Mudenge, B, Guti, V, Etyang, A, Agutu, C, Berkley, J, Maitland, K, Njuguna, P, Mwaringa, S, Etyang, T, Awuondo, K, Wale, S, Shangala, J, Kithunga, J, Mwarumba, S, Maitha, S Said, Mutai, R, Lewa, M Lozi, Mwambingu, G, Mwanzu, A, Kalama, C, Latham, H, Shikuku, J, Fondo, A, Njogu, A, Khadenge, C, Mwakisha, B, Siika, A, Wools?Kaloustian, K, Nyandiko, W, Cheruiyot, P, Sudoi, A, Wachira, S, Meli, B, Karoney, M, Nzioka, A, Tanui, M, Mokaya, M, Ekiru, W, Mboya, C, Mwimali, D, Mengich, C, Choge, J, Injera, W, Njenga, K, Cherutich, S, Orido, M Anyango, Lwande, G Omondi, Rutto, P, Mudogo, A, Kutto, I, Shali, A, Jaika, L, Jerotich, H, Pierre, M, Mallewa, J, Kaunda, S, Van Oosterhout, J, O'Hare, B, Heydermann, R, Gonzalez, C, Dzabala, N, Kelly, C, Denis, B, Selemani, G, Mipando, L Nyondo, Chirwa, E, Banda, P, Mvula, L, Msuku, H, Ziwoya, M, Manda, Y, Nicholas, S, Masesa, C, Mwalukomo, T, Makhaza, L, Sheha, I, Bwanali, J, Limbuni, M, Gibb, D, Thomason, M, Walker, As, Pett, S, Szubert, A, Griffiths, A, Wilkes, H, Rajapakse, C, Spyer, M, Prendergast, A, Klein, N, Rauchenberger, M, Van Looy, N, Little, E, Fairbrother, K, Cowan, F, Seeley, J, Bernays, S, Kawuma, R, Mupambireyi, Z, Kyomuhendo, F, Nakalanzi, S, Peshu, J, Ndaa, S, Chabuka, J, Mkandawire, N, Matandika, L, Kapuya, C, Weller, I, Malianga, E, Mwansambo, C, Miiro, F, Elyanu, P, Bukusi, E, Katabira, E, Mugurungi, O, Peto, T, Musoke, P, Matenga, J, Phiri, S, Lyall, H, Johnston, V, Fitzgerald, F, Post, F, Ssali, F, Arenas?Pinto, A, Turkova, A, and Bamford, A

Subjects
Cost benefit analysis, Practice guidelines (Medicine) -- Evaluation, HIV infection -- Diagnosis -- Care and treatment, Cost benefit analysis, Health
Abstract

: Introduction: Many HIV‐positive individuals in Africa have advanced disease when initiating antiretroviral therapy (ART) so have high risks of opportunistic infections and death. The REALITY trial found that an enhanced‐prophylaxis package including fluconazole reduced mortality by 27% in individuals starting ART with CD4 Methods: The REALITY trial enrolled from June 2013 to April 2015. A decision‐analytic model was developed to estimate the cost‐effectiveness of six management strategies in individuals initiating ART in the REALITY trial countries. Strategies included standard‐prophylaxis, enhanced‐prophylaxis, standard‐prophylaxis with fluconazole; and three CrAg testing strategies, the first stratifying individuals to enhanced‐prophylaxis (CrAg‐positive) or standard‐prophylaxis (CrAg‐negative), the second to enhanced‐prophylaxis (CrAg‐positive) or enhanced‐prophylaxis without fluconazole (CrAg‐negative) and the third to standard‐prophylaxis with fluconazole (CrAg‐positive) or without fluconazole (CrAg‐negative). The model estimated costs, life‐years and quality‐adjusted life‐years (QALY) over 48 weeks using three competing mortality risks: cryptococcal meningitis; tuberculosis, serious bacterial infection or other known cause; and unknown cause. Results: Enhanced‐prophylaxis was cost‐effective at cost‐effectiveness thresholds of US$300 and US$500 per QALY with an incremental cost‐effectiveness ratio (ICER) of US$157 per QALY in the CD4 Conclusions: The REALITY enhanced‐prophylaxis package in individuals with advanced HIV starting ART reduces morbidity and mortality, is practical to administer and is cost‐effective. Efforts should continue to ensure that components are accessed at lowest available prices., Introduction In low‐ and middle‐income settings, more than a third of HIV‐positive individuals starting antiretroviral therapy (ART) present with advanced disease (CD4 ≤ 200 cells/mm[sup.3]); over half of these have [...]

Published
2020
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13. Prevalence and Clinical Outcomes of Poor Immune Response Despite Virologically Suppressive Antiretroviral Therapy Among Children and Adolescents With Human Immunodeficiency Virus in Europe and Thailand: Cohort Study

Author

Chappell, E., Riordan, A., Jourdain, G., Soriano-Arandes, A., Ene, L., Scherpbier, H., Warszawski, J., Collins, I., Smit, C., Marques, L., Klein, N., Guillén, S., Judd, A., Thorne, C., Goodall, R., Königs, C., Spoulou, V., Prata, F., Goetghebuer, T., Chiappini, E., Galli, L., Naver, L., Giaquinto, C., Gibb, D., Marczynska, M., Okhonskaia, L., Klimkait, T., Lallemant, M., Ngo-Giang-Huong, N., Kiseleva, G., Malyuta, R., Volokha, A., Hainaut, M., Delforge, M., Le Chenadec, J., Ramos, E., Dialla, O., Wack, T., Laurent, C., Ait Si Selmi, L., Leymarie, I., Ait Benali, F., Brossard, M., Boufassa, L., Floch-Tudal, C., Firtion, G., Hau, I., Chace, A., Bolot, P., Blanche, S., Levine, M., Bicëtre, L., Fourcade, C., Heller-Roussin, B., Runel-Belliard, C., Tricoire, J., Chirouze, C., Reliquet, V., Brouard, J., Kebaili, K., Fialaire, P., Lalande, M., Schultze-Strasser, S., Baumann, U., Niehues, T., Neubert, J., Kobbe, R., Berlin, C., Feiterna-Sperling, C., Buchholz, B., Notheis, G., de Martino, M., Angelo Tovo, P., Patrizia, O., Larovere, D., Ruggeri, M., Faldella, G., Baldi, F., Badolato, R., Montagnani, C., Venturini, E., Lisi, C., Di Biagio, A., Taramasso, L., Giacomet, V., Erba, P., Esposito, S., Lipreri, R., Salvini, F., Tagliabue, C., Cellini, M., Bruzzese, E., Lo Vecchio, A., Rampon, O., Donà, D., Romano, A., Dodi, I., Maccabruni, A., Consolini, R., Bernardi, S., Tchidjou Kuekou, H., Genovese, O., Olmeo, P., Cristiano, L., Mazza, A., Gabiano, C., Garazzino, S., Pellegatta, A., Pajkrt, D., Weijsenfeld, A., de Boer CG, Jurriaans, S., Back, N., Zaaijer, H., Berkhout, B., Cornelissen, M., Schinkel, C., Wolthers, K., Fraaij, P., van Rossum AMC, van der Knaap LC, Visser, E., Koopmans, M., van Kampen JJA, Pas, S., Henriet, S., van de Flier, M., van Aerde, K., Strik-Albers, R., Rahamat-Langendoen, J., Stelma, F., Schölvinck, E., de Groot-de Jonge, H., Niesters, H., van Leer-Buter CC, Knoester, M., Bont, L., Geelen, S., Wolfs, T., Nauta, N., Ang, C., van Houdt, R., Pettersson, A., Vandenbroucke-Grauls, C., Reiss, P., Bezemer, D., van Sighem AI, Wit, F., Boender, T., Zaheri, S., Hillebregt, M., de Jong, A., Bergsma, D., Grivell, S., Jansen, A., Raethke, M., Meijering, R., de Groot, L., van den Akker, M., Bakker, Y., Claessen, E., El Berkaoui, A., Koops, J., Kruijne, E., Lodewijk, C., Munjishvili, L., Peeck, B., Ree, C., Regtop, R., Ruijs, Y., Rutkens, T., Schoorl, M., Timmerman, A., Tuijn, E., Veenenberg, L., van der Vliet, S., Wisse, A., Woudstra, T., Tuk, B., Popielska, J., Pokorska-Śpiewak, M., Ołdakowska, A., Zawadka, K., Coupland, U., DorobaLaura Marques, M., Teixeira, C., Fernandes, A., Voronin, E., Miloenko, M., Labutina, S., Tomás Ramos, J., Prieto, L., Luisa Navarro, M., Saavedra, J., Santos, M., Angeles Muñoz, M., Ruiz, B., Mc Phee CF, de Ory SJ, Alvarez, S., Ángel Roa, M., Beceiro, J., Martínez, J., Badillo, K., Apilanez, M., Pocheville, I., Garrote, E., Colino, E., Gómez Sirvent, J., Garzón, M., Román, V., Montesdeoca, A., Mateo, M., José Muñoz, M., Angulo, R., Neth, O., Falcón, L., Terol, P., Luis Santos, J., Moreno, D., Lendínez, F., Grande, A., José Romero, F., Lillo, M., Losada, B., Herranz, M., Bustillo, M., Guerrero, C., Collado, P., Antonio Couceiro, J., Pérez, A., Isabel Piqueras, A., Bretón, R., Segarra, I., Gavilán, C., Jareño, E., Montesinos, E., Dapena, M., Álvarez, C., Gloria Andrés, A., Marugán, V., Ochoa, C., Alfayate, S., Isabel Menasalvas, A., de Miguel, E., Aebi-Popp, K., Asner, S., Aubert, V., Battegay, M., Baumann, M., Bernasconi, E., Böni, J., Brazzola, P., Bucher, H., Calmy, A., Cavassini, M., Ciuffi, A., Duppenthaler, A., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Francini, K., Furrer, H., Fux, C., Grawe, C., Günthard, H., Haerry, D., Hasse, B., Hirsch, H., Hoffmann, M., Hösli, I., Kahlert, C., Kaiser, L., Keiser, O., Kovari, H., Kouyos, R., Ledergerber, B., Martinetti, G., de Tejada BM, Metzner, K., Müller, N., Nicca, D., Paioni, P., Pantaleo, G., Polli, C., Posfay-Barbe, K., Rauch, A., Rudin, C., Schmid, P., Scherrer, A., Speck, R., Tarr, P., Thanh Lecompte, M., Trkola, A., Vernazza, P., Wagner, N., Wandeler, G., Weber, R., Wyler, C., Yerly, S., Techakunakorn, P., Hansudewechakul, R., Kham, C., Wanchaitanawong, V., Theansavettrakul, S., Sai, M., Nanta, S., Ngampiyaskul, C., Phanomcheong, S., Hongsiriwon, S., Karnchanamayul, W., Kwanchaipanich, R., Kanjanavanit, S., Kamonpakorn, N., Nantarukchaikul, M., Layangool, P., Mekmullica, J., Lucksanapisitkul, P., Watanayothin, S., Lertpienthum, N., Warachit, B., Hanpinitsak, S., Potchalongsin, S., Thanasiri, P., Krikajornkitti, S., Attavinijtrakarn, P., Srirojana, S., Bunjongpak, S., Puangsombat, A., Na-Rajsima, S., Ananpatharachai, P., Akarathum, N., Phuket, V., Lawtongkum, W., Kheunjan, P., Suriyaboon, T., Saipanya, A., Than-In-At, K., Jaisieng, N., Suaysod, R., Chailoet, S., Naratee, N., Kawilapat, S., Kaleeva, T., Baryshnikova, Y., Soloha, S., Bashkatova, N., Raus, I., Glutshenko, O., Ruban, Z., Prymak, N., Bailey, H., Bamford, A., Butler, K., Doerholt, K., Doherty, C., Foster, C., Francis, K., Harrison, I., Kenny, J., Letting, G., Mcmaster, P., Murau, F., Nsangi, E., Peters, H., Prime, K., Shackley, F., Shingadia, D., Storey, S., Tudor-Williams, G., Turkova, A., Welch, S., Jeannie Collins, I., Cook, C., Crichton, S., Dobson, D., Fairbrother, K., M Gibb D, Harper, L., Le Prevost, M., Van Looy, N., Walsh, A., Thrasyvoulou, L., Bernatoniene, J., Manyika, F., Sharpe, G., Subramaniam, B., Sloper, K., Fidler, K., Hague, R., Price, V., Clapson, M., Flynn, J., Cardoso, A., Abou-Rayyah, M., Gurtin, D., Yeadon, S., Segal, S., Ball, C., Hawkins, S., Dowie, M., Bandi, S., Percival, E., Eisenhut, M., Duncan, K., Clough, S., Anguvaa, L., Conway, S., Flood, T., Pickering, A., Murphy, C., Daniels, J., Lees, Y., Thompson, F., Williams, B., Pope, S., Cliffe, L., Smyth, A., Southall, S., Freeman, A., Freeman, H., Christie, S., Gordon, A., Rogahn, D., Clarke, L., Jones, L., Offerman, B., Greenberg, M., Benson, C., Ibberson, L., Faust, S., Hancock, J., Sharland, M., Lyall, H., Monrose, C., Seery, P., Menson, E., Callaghan, A., Bridgwood, A., Evans, J., Blake, E., Yannoulias, A., Critchton, S., Duff, C., Gomezpena, D., Lundin, R., Mangiarini, L., Nardone, A., Posfay Barbe, Klara, Universidad de Alcalá - University of Alcalá (UAH), Department of Sciences for Woman and Child's Health, Università degli Studi di Firenze = University of Florence (UniFI), Épidémiologie clinique, santé mère-enfant et VIH en Asie du Sud-Est (IRD_PHPT), Harvard University-Chiang Mai University (CMU), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier de Saint-Denis [Ile-de-France], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), service de maladies infectieuses CHU J Minjoz Besancon, Service des maladies infectieuses et tropicales [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Pédiatrie Médicale [Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service d'hématologie : Immuno-Hématologie pédiatrique et transplantation de moelle osseuse, Hôpital Debrousse, Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Universitätsklinikum Frankfurt, Infectious Diseases, San Martino Hospital, Università degli studi di Genova = University of Genoa (UniGe), Department of Maternal and Pediatric Sciences, University of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Maternal-Infantile Department, Unit of Paediatrics and Oncohematology, University Hospital of Parma, Department of Infectious Diseases, IRCCS S. Matteo, Department of Paediatrics, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), Dipartimento di Ingegneria [Benevento], Università degli Studi del Sannio, University of Twente, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Laboratory for Infectious Diseases and Perinatal Screening, Center for Infectious Disease Control, National Institute for Public Health and the Environment [Bilthoven] (RIVM), Architecture et réactivité de l'ARN (ARN), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), Synthèse, Structure et Propriétés de Matériaux Fonctionnels (STEP), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Département Interfaces pour l'énergie, la Santé et l'Environnement (DIESE), Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Stichting HIV Monitoring, Universidade Federal do Ceará = Federal University of Ceará (UFC), Departamento de Química Orgánica, Universidade de Vigo, Polytechnical University of Valencia, Fac Biol, Dept Genet, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), University of the Basque Country/Euskal Herriko Unibertsitatea (UPV/EHU), Service des maladies infectieuses, Hôpitaux Universitaires de Genève (HUG), University of Basel (Unibas), Dysfonctions métaboliques et diabètes: Mécanismes et approches thérapeutiques, Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM), University Heart Centre Freiburg - Bad Krozingen, Prapokklao Hospital [Chanthaburi, Thailand], Nakornping Hospital [Chiang Mai, Thailand], Samutsakhon Hospital [Samutsakhon, Thailand], Kalasin Hospital [Kalasin, Thailand], Sanpatong Hospital [Chiang Mai, Thailand], Chiang Mai University (CMU), Microbiology Department, St. Jame's Hospital, University of Edinburgh, Infectious Diseases and Microbiology Unit, Great Ormond Street Hospital for Children [London] (GOSH)-Institute of Child Health, European Synchrotron Radiation Facility (ESRF), Centre for Ecology and Hydrology [Bangor] (CEH), Natural Environment Research Council (NERC), Jet Propulsion Laboratory (JPL), NASA-California Institute of Technology (CALTECH), University of London [London], London South Bank University (LSBU), Dipartimento di Pediatria, Azienda Ospedaliera di Padova, Université Grenoble Alpes - UFR Pharmacie (UGA UFRP), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), The European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) Study Group in EuroCoord, Florence University, Harvard University [Cambridge]-Chiang Mai University (CMU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), University of Genoa (UNIGE), Catholic University of Rome, University of Twente [Netherlands], Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), University of the Basque Country [Bizkaia] (UPV/EHU), Université Nice Sophia Antipolis (... - 2019) (UNS), Pediatrics, Virology, Chappell, Elizabeth, Riordan, Andrew, Jourdain, Gonzague, Soriano-Arandes, Antoni, Ene, Luminita, J Scherpbier, Henriette, Warszawski, Josiane, J Collins, Intira, Smit, Colette, Marques, Laura, Klein, Nigel, Guillén, Sara, Judd, Ali, Thorne, Claire, Goodall, Ruth, Königs, Christoph, Spoulou, Vana, Prata, Filipa, Goetghebuer, Tessa, Chiappini, Elena, Galli, Luisa, Naver, Lar, Giaquinto, Carlo, M Gibb, Diana, Marczynska, Magdalena, Okhonskaia, Liubov, Klimkait, Thoma, Lallemant, Marc, Ngo-Giang-Huong, Nicole, Kiseleva, Galyna, Malyuta, Ruslan, Volokha, Alla, Hainaut, Marc, Delforge, Marc, Le Chenadec, Jerome, Ramos, Elisa, Dialla, Olivia, Wack, Thierry, Laurent, Corine, Ait Si Selmi, Lamya, Leymarie, Isabelle, Ait Benali, Fazia, Brossard, Maud, Boufassa, Leila, Floch-Tudal, Corinne, Firtion, Ghislaine, Hau, Isabelle, Chace, Anne, Bolot, Pascal, Blanche, Stéphane, Levine, Martine, Kremlin Bicëtre, Le, Fourcade, Corinne, Heller-Roussin, Brigitte, Runel-Belliard, Camille, Tricoire, Joëlle, Chirouze, Catherine, Reliquet, Véronique, Brouard, Jacque, Kebaili, Kamila, Fialaire, Pascale, Lalande, Muriel, Schultze-Strasser, Stephan, Baumann, U, Niehues, T, Neubert, J, Kobbe, R, Berlin, Charite, Feiterna-Sperling, C, Königs, C, Buchholz, B, Notheis, G, de Martino, Maurizio, Angelo Tovo, Pier, Patrizia, Osimani, Larovere, Domenico, Ruggeri, Maurizio, Faldella, Giacomo, Baldi, Francesco, Badolato, Raffaele, Montagnani, Carlotta, Venturini, Elisabetta, Lisi, Catiuscia, Di Biagio, Antonio, Taramasso, Lucia, Giacomet, Vania, Erba, Paola, Esposito, Susanna, Lipreri, Rita, Salvini, Filippo, Tagliabue, Claudia, Cellini, Monica, Bruzzese, Eugenia, LO VECCHIO, Andrea, Paediatric Infectious Diseases / Rheumatology / Immunology, Amsterdam institute for Infection and Immunity, AII - Infectious diseases, Amsterdam Reproduction & Development (AR&D), APH - Aging & Later Life, Infectious diseases, and Global Health

Subjects
0301 basic medicine, medicine.medical_treatment, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], HIV Infections, Rate ratio, Cohort Studies, 0302 clinical medicine, Pregnancy, Antiretroviral Therapy, Highly Active, Prevalence, 030212 general & internal medicine, Child, poor immune response, ddc:618, Immunosuppression, Viral Load, Hepatitis B, Thailand, 3. Good health, Europe, Thailand/epidemiology, Infectious Diseases, Cohort, Coinfection, Female, Cohort study, Adult, Microbiology (medical), viral suppression, medicine.medical_specialty, Adolescent, Anti-HIV Agents, antiretroviral therapy, 030106 microbiology, Europe/epidemiology, 03 medical and health sciences, children, Acquired immunodeficiency syndrome (AIDS), SDG 3 - Good Health and Well-being, Internal medicine, medicine, Humans, HIV, Aged, Settore MED/38 - Pediatria Generale e Specialistica, business.industry, Immunity, medicine.disease, HIV Infections/drug therapy/epidemiology, CD4 Lymphocyte Count, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Anti-HIV Agents/therapeutic use, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Background In human immunodeficiency virus (HIV)–positive adults, low CD4 cell counts despite fully suppressed HIV-1 RNA on antiretroviral therapy (ART) have been associated with increased risk of morbidity and mortality. We assessed the prevalence and outcomes of poor immune response (PIR) in children receiving suppressive ART. Methods Sixteen cohorts from the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) contributed data. Children Results Of 2318 children included, median age was 6.4 years and 68% had advanced/severe immunosuppression at ART initiation. At 1 year of VS, 12% had PIR. In multivariable analysis, PIR was associated with older age and worse immunological stage at ART start, hepatitis B coinfection, and residing in Thailand (all P ≤ .03). Rates of AIDS/death (95% confidence interval) per 100 000 person-years were 1052 (547, 2022) among PIR versus 261 (166, 409) among immune responders; rate ratio of 4.04 (1.83, 8.92; P < .001). Conclusions One in eight children in our cohort experienced PIR despite sustained VS. While the overall rate of AIDS/death was low, children with PIR had a 4-fold increase in risk of event as compared with immune responders.

Published
2020

14. No need for secondary Pneumocystis jirovecii pneumonia prophylaxis in adult people living with HIV from Europe on ART with suppressed viraemia and a CD4 cell count greater than 100 cells/µL

Author

Atkinson, A, Miro, J, Mocroft, A, Reiss, P, Kirk, O, Morlat, P, Ghosn, J, Stephan, C, Mussini, C, Antoniadou, A, Doerholt, K, Girardi, E, De Wit, S, Kraus, D, Zwahlen, M, Furrer, H, Castagna, A, Fatkenheuer, G, Raben, D, Teira, R, Zangerle, R, Judd, A, Touloumi, G, Warszawski, J, Meyer, L, Dabis, F, Krause, M, Leport, C, Wittkop, L, Wit, F, Prins, M, Bucher, H, Gibb, D, Del Amo, J, Obel, N, Thorne, C, Perez-Hoyos, S, Hamouda, O, Bartmeyer, B, Chkhartishvili, N, Noguera-Julian, A, Antinori, A, d'Arminio Monforte, A, Brockmeyer, N, Prieto, L, Conejo, P, Soriano-Arandes, A, Battegay, M, Kouyos, R, Casabona, J, Goetghebuer, T, Sonnerborg, A, Torti, C, Sabin, C, Garrido, M, Haerry, D, Costagliola, D, d'Arminio-Monforte, A, del Amo, J, Chene, G, Barger, D, Schwimmer, C, Termote, M, Frederiksen, C, Brandt, R, Berenguer, J, Bohlius, J, Bouteloup, V, Cozzi-Lepri, A, Davies, M, Dorrucci, M, Dunn, D, Egger, M, Guiguet, M, Grabar, S, Lambotte, O, Leroy, V, Lodi, S, Matheron, S, Monge, S, Nakagawa, F, Paredes, R, Phillips, A, Puoti, M, Rohner, E, Schomaker, M, Smit, C, Sterne, J, Thiebaut, R, Wqetu, C, van der Valk, M, Atkinson A., Miro J. M., Mocroft A., Reiss P., Kirk O., Morlat P., Ghosn J., Stephan C., Mussini C., Antoniadou A., Doerholt K., Girardi E., De Wit S., Kraus D., Zwahlen M., Furrer H., Castagna A., Fatkenheuer G., Raben D., Teira R., Zangerle R., Judd A., Touloumi G., Warszawski J., Meyer L., Dabis F., Krause M. M., Leport C., Wittkop L., Wit F., Prins M., Bucher H., Gibb D., Del Amo J., Obel N., Thorne C., Perez-Hoyos S., Hamouda O., Bartmeyer B., Chkhartishvili N., Noguera-Julian A., Antinori A., d'Arminio Monforte A., Brockmeyer N., Prieto L., Conejo P. R., Soriano-Arandes A., Battegay M., Kouyos R., Casabona J., Goetghebuer T., Sonnerborg A., Torti C., Sabin C., Garrido M., Haerry D., Costagliola D., d'Arminio-Monforte A., del Amo J., Chene G., Barger D., Schwimmer C., Termote M., Frederiksen C. M., Brandt R. S., Berenguer J., Bohlius J., Bouteloup V., Cozzi-Lepri A., Davies M. -A., Dorrucci M., Dunn D., Egger M., Guiguet M., Grabar S., Lambotte O., Leroy V., Lodi S., Matheron S., Monge S., Nakagawa F., Paredes R., Phillips A., Puoti M., Rohner E., Schomaker M., Smit C., Sterne J., Thiebaut R., Wqetu C., van der Valk M., Atkinson, A, Miro, J, Mocroft, A, Reiss, P, Kirk, O, Morlat, P, Ghosn, J, Stephan, C, Mussini, C, Antoniadou, A, Doerholt, K, Girardi, E, De Wit, S, Kraus, D, Zwahlen, M, Furrer, H, Castagna, A, Fatkenheuer, G, Raben, D, Teira, R, Zangerle, R, Judd, A, Touloumi, G, Warszawski, J, Meyer, L, Dabis, F, Krause, M, Leport, C, Wittkop, L, Wit, F, Prins, M, Bucher, H, Gibb, D, Del Amo, J, Obel, N, Thorne, C, Perez-Hoyos, S, Hamouda, O, Bartmeyer, B, Chkhartishvili, N, Noguera-Julian, A, Antinori, A, d'Arminio Monforte, A, Brockmeyer, N, Prieto, L, Conejo, P, Soriano-Arandes, A, Battegay, M, Kouyos, R, Casabona, J, Goetghebuer, T, Sonnerborg, A, Torti, C, Sabin, C, Garrido, M, Haerry, D, Costagliola, D, d'Arminio-Monforte, A, del Amo, J, Chene, G, Barger, D, Schwimmer, C, Termote, M, Frederiksen, C, Brandt, R, Berenguer, J, Bohlius, J, Bouteloup, V, Cozzi-Lepri, A, Davies, M, Dorrucci, M, Dunn, D, Egger, M, Guiguet, M, Grabar, S, Lambotte, O, Leroy, V, Lodi, S, Matheron, S, Monge, S, Nakagawa, F, Paredes, R, Phillips, A, Puoti, M, Rohner, E, Schomaker, M, Smit, C, Sterne, J, Thiebaut, R, Wqetu, C, van der Valk, M, Atkinson A., Miro J. M., Mocroft A., Reiss P., Kirk O., Morlat P., Ghosn J., Stephan C., Mussini C., Antoniadou A., Doerholt K., Girardi E., De Wit S., Kraus D., Zwahlen M., Furrer H., Castagna A., Fatkenheuer G., Raben D., Teira R., Zangerle R., Judd A., Touloumi G., Warszawski J., Meyer L., Dabis F., Krause M. M., Leport C., Wittkop L., Wit F., Prins M., Bucher H., Gibb D., Del Amo J., Obel N., Thorne C., Perez-Hoyos S., Hamouda O., Bartmeyer B., Chkhartishvili N., Noguera-Julian A., Antinori A., d'Arminio Monforte A., Brockmeyer N., Prieto L., Conejo P. R., Soriano-Arandes A., Battegay M., Kouyos R., Casabona J., Goetghebuer T., Sonnerborg A., Torti C., Sabin C., Garrido M., Haerry D., Costagliola D., d'Arminio-Monforte A., del Amo J., Chene G., Barger D., Schwimmer C., Termote M., Frederiksen C. M., Brandt R. S., Berenguer J., Bohlius J., Bouteloup V., Cozzi-Lepri A., Davies M. -A., Dorrucci M., Dunn D., Egger M., Guiguet M., Grabar S., Lambotte O., Leroy V., Lodi S., Matheron S., Monge S., Nakagawa F., Paredes R., Phillips A., Puoti M., Rohner E., Schomaker M., Smit C., Sterne J., Thiebaut R., Wqetu C., and van der Valk M.

Abstract

Introduction: Since the beginning of the HIV epidemic in resource-rich countries, Pneumocystis jirovecii pneumonia (PjP) is one of the most frequent opportunistic AIDS-defining infections. The Collaboration of Observational HIV Epidemiological Research Europe (COHERE) has shown that primary Pneumocystis jirovecii Pneumonia (PjP) prophylaxis can be safely withdrawn in patients with CD4 counts of 100 to 200 cells/µL if plasma HIV-RNA is suppressed on combination antiretroviral therapy. Whether this holds true for secondary prophylaxis is not known, and this has proved difficult to determine due to the much lower population at risk. Methods: We estimated the incidence of secondary PjP by including patient data collected from 1998 to 2015 from the COHERE cohort collaboration according to time-updated CD4 counts, HIV-RNA and use of PjP prophylaxis in persons >16 years of age. We fitted a Poisson generalized additive model in which the smoothed effect of CD4 was modelled by a restricted cubic spline, and HIV-RNA was stratified as low (<400), medium (400 to 10,000) or high (>10,000copies/mL). Results: There were 373 recurrences of PjP during 74,295 person-years (py) in 10,476 patients. The PjP incidence in the different plasma HIV-RNA strata differed significantly and was lowest in the low stratum. For patients off prophylaxis with CD4 counts between 100 and 200 cells/µL and HIV-RNA below 400 copies/mL, the incidence of recurrent PjP was 3.9 (95% CI: 2.0 to 5.8) per 1000 py, not significantly different from patients on prophylaxis in the same stratum (1.9, 95% CI: 0.1 to 3.7). Conclusions: HIV viraemia importantly affects the risk of recurrent PjP. In virologically suppressed patients on ART with CD4 counts of 100 to 200/µL, the incidence of PjP off prophylaxis is below 10/1000 py. Secondary PjP prophylaxis may be safely withheld in such patients. While European guidelines recommend discontinuing secondary PjP prophylaxis only if CD4 counts ris

Published
2021

15. Paediatric European Network for Treatment of AIDS (PENTA) guidelines for treatment of paediatric HIV‐1 infection 2015: optimizing health in preparation for adult life

Author

Bamford, A, Turkova, A, Lyall, H, Foster, C, Klein, N, Bastiaans, D, Burger, D, Bernadi, S, Butler, K, Chiappini, E, Clayden, P, Della Negra, M, Giacomet, V, Giaquinto, C, Gibb, D, Galli, L, Hainaut, M, Koros, M, Marques, L, Nastouli, E, Niehues, T, Noguera‐Julian, A, Rojo, P, Rudin, C, Scherpbier, HJ, Tudor‐Williams, G, and Welch, SB

Published
2018
Full Text
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16. No need for secondary Pneumocystis jirovecii pneumonia prophylaxis in adult people living with HIV from Europe on ART with suppressed viraemia and a CD4 cell count greater than 100 cells/µL

Author

Atkinson, A., Miro, J. M., Mocroft, A., Reiss, P., Kirk, O., Morlat, P., Ghosn, J., Stephan, C., Mussini, C., Antoniadou, A., Doerholt, K., Girardi, E., De Wit, S., Kraus, D., Zwahlen, M., Furrer, H., Castagna, A., Fatkenheuer, G., Raben, D., Teira, R., Zangerle, R., Judd, A., Touloumi, G., Warszawski, J., Meyer, L., Dabis, F., Krause, M. M., Leport, C., Wittkop, L., Wit, F., Prins, M., Bucher, H., Gibb, D., Del Amo, J., Obel, N., Thorne, C., Perez-Hoyos, S., Hamouda, O., Bartmeyer, B., Chkhartishvili, N., Noguera-Julian, A., Antinori, A., d'Arminio Monforte, A., Brockmeyer, N., Prieto, L., Conejo, P. R., Soriano-Arandes, A., Battegay, M., Kouyos, R., Casabona, J., Goetghebuer, T., Sonnerborg, A., Torti, C., Sabin, C., Garrido, M., Haerry, D., Costagliola, D., d'Arminio-Monforte, A., del Amo, J., Chene, G., Barger, D., Schwimmer, C., Termote, M., Frederiksen, C. M., Brandt, R. S., Berenguer, J., Bohlius, J., Bouteloup, V., Cozzi-Lepri, A., Davies, M. -A., Dorrucci, M., Dunn, D., Egger, M., Guiguet, M., Grabar, S., Lambotte, O., Leroy, V., Lodi, S., Matheron, S., Monge, S., Nakagawa, F., Paredes, R., Phillips, A., Puoti, M., Rohner, E., Schomaker, M., Smit, C., Sterne, J., Thiebaut, R., Wqetu, C., van der Valk, M., Global Health, Infectious diseases, AII - Infectious diseases, APH - Aging & Later Life, Atkinson, A, Miro, J, Mocroft, A, Reiss, P, Kirk, O, Morlat, P, Ghosn, J, Stephan, C, Mussini, C, Antoniadou, A, Doerholt, K, Girardi, E, De Wit, S, Kraus, D, Zwahlen, M, Furrer, H, Castagna, A, Fatkenheuer, G, Raben, D, Teira, R, Zangerle, R, Judd, A, Touloumi, G, Warszawski, J, Meyer, L, Dabis, F, Krause, M, Leport, C, Wittkop, L, Wit, F, Prins, M, Bucher, H, Gibb, D, Del Amo, J, Obel, N, Thorne, C, Perez-Hoyos, S, Hamouda, O, Bartmeyer, B, Chkhartishvili, N, Noguera-Julian, A, Antinori, A, d'Arminio Monforte, A, Brockmeyer, N, Prieto, L, Conejo, P, Soriano-Arandes, A, Battegay, M, Kouyos, R, Casabona, J, Goetghebuer, T, Sonnerborg, A, Torti, C, Sabin, C, Garrido, M, Haerry, D, Costagliola, D, d'Arminio-Monforte, A, del Amo, J, Chene, G, Barger, D, Schwimmer, C, Termote, M, Frederiksen, C, Brandt, R, Berenguer, J, Bohlius, J, Bouteloup, V, Cozzi-Lepri, A, Davies, M, Dorrucci, M, Dunn, D, Egger, M, Guiguet, M, Grabar, S, Lambotte, O, Leroy, V, Lodi, S, Matheron, S, Monge, S, Nakagawa, F, Paredes, R, Phillips, A, Puoti, M, Rohner, E, Schomaker, M, Smit, C, Sterne, J, Thiebaut, R, Wqetu, C, and van der Valk, M

Subjects
Adult, medicine.medical_specialty, Adolescent, opportunistic infection, Population, Human immunodeficiency virus (HIV), HIV Infections, 610 Medicine & health, Pneumocystis carinii, medicine.disease_cause, Young Adult, 03 medical and health sciences, 0302 clinical medicine, 360 Social problems & social services, Internal medicine, Epidemiology, medicine, Humans, Opportunistic infections, Viremia, 030212 general & internal medicine, education, Research Articles, education.field_of_study, 030505 public health, business.industry, Pneumonia, Pneumocystis, Incidence (epidemiology), prophylaxi, Pneumocystis jirovecii Pneumonia, Public Health, Environmental and Occupational Health, opportunistic infections, Pneumocystis jirovecii pneumonia, CD4 Lymphocyte Count, 3. Good health, Discontinuation, Europe, Infectious Diseases, Cohort, Infeccions per VIH, prophylaxis, 0305 other medical science, business, Viral load, Infeccions oportunistes, Research Article, HIV infections
Abstract

Introduction: Since the beginning of the HIV epidemic in resource-rich countries, Pneumocystis jirovecii pneumonia (PjP) is one of the most frequent opportunistic AIDS-defining infections. The Collaboration of Observational HIV Epidemiological Research Europe (COHERE) has shown that primary Pneumocystis jirovecii Pneumonia (PjP) prophylaxis can be safely withdrawn in patients with CD4 counts of 100 to 200 cells/µL if plasma HIV-RNA is suppressed on combination antiretroviral therapy. Whether this holds true for secondary prophylaxis is not known, and this has proved difficult to determine due to the much lower population at risk. Methods: We estimated the incidence of secondary PjP by including patient data collected from 1998 to 2015 from the COHERE cohort collaboration according to time-updated CD4 counts, HIV-RNA and use of PjP prophylaxis in persons >16 years of age. We fitted a Poisson generalized additive model in which the smoothed effect of CD4 was modelled by a restricted cubic spline, and HIV-RNA was stratified as low (10,000copies/mL). Results: There were 373 recurrences of PjP during 74,295 person-years (py) in 10,476 patients. The PjP incidence in the different plasma HIV-RNA strata differed significantly and was lowest in the low stratum. For patients off prophylaxis with CD4 counts between 100 and 200 cells/µL and HIV-RNA below 400 copies/mL, the incidence of recurrent PjP was 3.9 (95% CI: 2.0 to 5.8) per 1000 py, not significantly different from patients on prophylaxis in the same stratum (1.9, 95% CI: 0.1 to 3.7). Conclusions: HIV viraemia importantly affects the risk of recurrent PjP. In virologically suppressed patients on ART with CD4 counts of 100 to 200/µL, the incidence of PjP off prophylaxis is below 10/1000 py. Secondary PjP prophylaxis may be safely withheld in such patients. While European guidelines recommend discontinuing secondary PjP prophylaxis only if CD4 counts rise above 200 cells/mL, the latest US Guidelines consider secondary prophylaxis discontinuation even in patients with a CD4 count above 100 cells/µL and suppressed viral load. Our results strengthen and support this US recommendation. Keywords: opportunistic infections; Pneumocystis jirovecii pneumonia; prophylaxis

Published
2021

17. Abacavir pharmacokinetics in African children living with HIV: A pooled analysis describing the effects of age, malnutrition and common concomitant medications

Author

Tikiso, T., McIlleron, H., Burger, D.M., Gibb, D., Rabie, H., Lee, J., Lallemant, M., Cotton, M.F., Archary, M., Hennig, S., Denti, P., Tikiso, T., McIlleron, H., Burger, D.M., Gibb, D., Rabie, H., Lee, J., Lallemant, M., Cotton, M.F., Archary, M., Hennig, S., and Denti, P.

Abstract

Item does not contain fulltext, AIMS: Abacavir is part of WHO-recommended regimens to treat HIV in children under 15 years of age. In a pooled analysis across four studies, we describe abacavir population pharmacokinetics to investigate the influence of age, concomitant medications, malnutrition and formulation. METHODS: A total of 230 HIV-infected African children were included, with median (range) age of 2.1 (0.1-12.8) years and weight of 9.8 (2.5-30.0) kg. The population pharmacokinetics of abacavir was described using nonlinear mixed-effects modelling. RESULTS: Abacavir pharmacokinetics was best described by a two-compartment model with first-order elimination, and absorption described by transit compartments. Clearance was predicted around 54% of its mature value at birth and 90% at 10 months. The estimated typical clearance at steady state was 10.7 L/h in a child weighing 9.8 kg co-treated with lopinavir/ritonavir, and was 12% higher in children receiving efavirenz. During coadministration of rifampicin-based antituberculosis treatment and super-boosted lopinavir in a 1:1 ratio with ritonavir, abacavir exposure decreased by 29.4%. Malnourished children living with HIV had higher abacavir exposure initially, but this effect waned with nutritional rehabilitation. An additional 18.4% reduction in clearance after the first abacavir dose was described, suggesting induction of clearance with time on lopinavir/ritonavir-based therapy. Finally, absorption of the fixed dose combination tablet was 24% slower than the abacavir liquid formulation. CONCLUSION: In this pooled analysis we found that children on lopinavir/ritonavir or efavirenz had similar abacavir exposures, while concomitant TB treatment and super-boosted lopinavir gave significantly reduced abacavir concentrations.

Published
2022

18. Pharmacokinetics of First-Line Drugs in Children With Tuberculosis, Using World Health Organization-Recommended Weight Band Doses and Formulations

Author

Chabala, C., Turkova, A., Hesseling, A.C., Zimba, K.M., Zalm, M. van der, Kapasa, M., Palmer, M., Chirehwa, M., Wiesner, L., Wobudeya, E., Kinikar, A., Mave, V., Hissar, S., Choo, L., LeBeau, K., Mulenga, V., Aarnoutse, R.E., Gibb, D., McIlleron, H., Chabala, C., Turkova, A., Hesseling, A.C., Zimba, K.M., Zalm, M. van der, Kapasa, M., Palmer, M., Chirehwa, M., Wiesner, L., Wobudeya, E., Kinikar, A., Mave, V., Hissar, S., Choo, L., LeBeau, K., Mulenga, V., Aarnoutse, R.E., Gibb, D., and McIlleron, H.

Abstract

Item does not contain fulltext, BACKGROUND: Dispersible pediatric fixed-dose combination (FDC) tablets delivering higher doses of first-line antituberculosis drugs in World Health Organization-recommended weight bands were introduced in 2015. We report the first pharmacokinetic data for these FDC tablets in Zambian and South African children in the treatment-shortening SHINE trial. METHODS: Children weighing 4.0-7.9, 8.0-11.9, 12.0-15.9, or 16.0-24.9 kg received 1, 2, 3, or 4 tablets daily, respectively (rifampicin/isoniazid/pyrazinamide [75/50/150 mg], with or without 100 mg ethambutol, or rifampicin/isoniazid [75/50 mg]). Children 25.0-36.9 kg received doses recommended for adults <37 kg (300, 150, 800, and 550 mg/d, respectively, for rifampicin, isoniazid, pyrazinamide, and ethambutol). Pharmacokinetics were evaluated after at least 2 weeks of treatment. RESULTS: In the 77 children evaluated, the median age (interquartile range) was 3.7 (1.4-6.6) years; 40 (52%) were male and 20 (26%) were human immunodeficiency virus positive. The median area under the concentration-time curve from 0 to 24 hours for rifampicin, isoniazid, pyrazinamide, and ethambutol was 32.5 (interquartile range, 20.1-45.1), 16.7 (9.2-25.9), 317 (263-399), and 9.5 (7.5-11.5) mg⋅h/L, respectively, and lower in children than in adults for rifampicin in the 4.0-7.9-, 8-11.9-, and ≥25-kg weight bands, isoniazid in the 4.0-7.9-kg and ≥25-kg weight bands, and ethambutol in all 5 weight bands. Pyrazinamide exposures were similar to those in adults. CONCLUSIONS: Recommended weight band-based FDC doses result in lower drug exposures in children in lower weight bands and in those ≥25 kg (receiving adult doses). Further adjustments to current doses are needed to match current target exposures in adults. The use of ethambutol at the current World Health Organization-recommended doses requires further evaluation.

Published
2022

19. Children living with HIV in Europe: do migrants have worse treatment outcomes?

Author

Chappell, E., Kohns Vasconcelos, M., Goodall, R. L., Galli, L., Goetghebuer, T., Noguera-Julian, A., Rodrigues, L. C., Scherpbier, H., Smit, C., Bamford, A., Crichton, S., Navarro, M. L., Ramos, J. T., Warszawski, J., Spolou, V., Chiappini, E., Venturini, E., Prata, F., Kahlert, C., Marczynska, M., Marques, L., Naver, L., Thorne, C., Gibb, D. M., Giaquinto, C., Judd, A., Collins, I. J., Goodall, R., Rodrigues, L., Duff, C., Gomezpena, D., Jackson, C., Lundin, R., Mangiarini, L., Milanzi, E., Nardone, A., Hainaut, M., Van der Kelen, E., Delforge, M., Le Chenadec, J., Ramos, E., Dialla, O., Wack, T., Laurent, C., Ait si Selmi, L., Leymarie, I., Ait Benali, F., Brossard, M., Boufassa, L., Floch-Tudal, C., Firtion, G., Hau, I., Chace, A., Bolot, P., Blanche, S., Granier, M., Labrune, P., Lachassine, E., Dollfus, C., Levine, M., Fourcade, C., Heller-Roussin, B., Runel-Belliard, C., Tricoire, J., Monpoux, F., Chirouze, C., Reliquet, V., Brouard, J., Kebaili, K., Fialaire, P., de Villeneuve, A., Lalande, M., de Flandres, J., Mazingue, F., Partisani, M. L., de Martino, M., Angelo Tovo, P., Gabiano, C., Carloni, I., Larovere, D., Baldi, F., Miniaci, A., Pession, A., Badolato, R., Panto, G., Anastasio, E., Montagnani, C., Bianchi, L., Allodi, A., Di Biagio, A., Grignolo, S., Giacomet, V., Marchisio, P., Banderali, G., Tagliabue, C., Cellini, M., Bruzzese, E., Di Costanzo, P., Lo Vecchio, A., Dona, D., Rampon, O., Romano, A., Dodi, I., Esposito, S., Zuccaro, V., Zanaboni, D., Consolini, R., Bernardi, S., Genovese, O., Cristiano, L., Mazza, A., Garazzino, S., Mignone, F., Silvestro, E., Portelli, V., Kinderziekenhuis, E., van der Kuip, M., Pajkrt, D., Scherpbier, H. J., de Boer, C., Weijsenfeld, A. M., Jurriaans, S., Back, N. K. T., Zaaijer, H. L., Berkhout, B., Cornelissen, M. T. E., Schinkel, C. J., Wolthers, K. C., Fraaij, P. L. A., van Rossum, A. M. C., Vermont, C. L., van der Knaap, L. C., Visser, E., Boucher, C. A. B., Koopmans, M. P. G., van Kampen, J. J. A., Henriet, S. S. V., van Aerde, M. K., Strik-Albers, R., Rahamat-Langendoen, J., Stelma, F. F., Burger, D., Scholvinck, E. H., de Groot-de Jonge, H., Niesters, H. G. M., van Leer-Buter, C. C., Knoester, M., Bont, L. J., Geelen, S. P. M., Loeffen, Y. G. T., Wolfs, T. F. W., Nauta, N., Schuurman, R., Hofstra, L. M., Wensing, A. M. J., Reiss, P., Zaheri, S., Boyd, A. C., Bezemer, D. O., van Sighem, A. I., Wit, F. W. M. N., Hillebregt, M. M. J., Woudstra, T. J., Bergsma, D., van de Sande, L., Rutkens, T., van der Vliet, S., Lelivelt, K. J., Scheijgrond, A., de Groot, L., van den Akker, M., Bakker, Y., EI Berkaoui, A., Bezemer, M., Bretin, N., Djoechro, E., Groters, M., Kruijne, E., Lodewijk, C., Lucas, E., Munjishvili, L., Paling, F., Peeck, B., Ree, C., Regtop, R., Ruijs, Y., Schoorl, M., Schnorr, P., Tuijn, E., Veenenberg, L., Visser, K. M., Witte, E. C., Popielska, J., Pokorska-Spiewak, M., Oldakowska, A., Zawadka, K., Coupland, U., Doroba, M., Teixeira, C., Fernandes, A., Soler-Palacin, P., Antoinette Frick, M., Perez-Hoyos, S., Mur, A., Lopez, N., Mendez, M., Mayol, L., Vallmanya, T., Calavia, O., Garcia, L., Coll, M., Pineda, V., Rius, N., Rovira, N., Duenas, J., Fortuny, C., Jose Mellado, M., Escosa, L., Garcia Hortelano, M., Sainz, T., Gonzalez-Tome, M. I., Rojo, P., Blazquez, D., Prieto-Tato, L., Epalza, C., Tomas Ramos, J., Guillen, S., Saavedra, J., Santos, M., Santiago, B., de Ory, S. J., Carrasco, I., Munoz-Fernandez, M. A., Angel Roa, M., Penin, M., Martinez, J., Badillo, K., Onate, E., Pocheville, I., Garrote, E., Colino, E., Gomez Sirvent, J., Garzon, M., Roman, V., Angulo, R., Neth, O., Falcon, L., Terol, P., Luis Santos, J., Moreno, D., Lendinez, F., Peromingo, E., Uberos, J., Ruiz, B., Grande, A., Jose Romero, F., Perez, C., Lillo, M., Losada, B., Herranz, M., Bustillo, M., Collado, P., Antonio Couceiro, J., Vila, L., Calvino, C., Isabel Piqueras, A., Oltra, M., Gavilan, C., Montesinos, E., Dapena, M., Alvarez, C., Jimenez, B., Gloria Andres, A., Marugan, V., Ochoa, C., Alfayate, S., Isabel Menasalvas, A., del Prado, Y. R., Navernaver, L., Soeria-Atmadja, S., Belfrage, E., Hagas, V., Aebi-Popp, K., Anagnostopoulos, A., Battegay, M., Baumann, M., Bernasconi, E., Boni, J., Braun, D. L., Bucher, H. C., Calmy, A., Cavassini, M., Ciuffi, A., Crisinel, P. A., Duppenthaler, A., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Francini, K., Furrer, H., Fux, C. A., Gunthard, H. F., Haerry, D., Hasse, B., Hirsch, H. H., Hoffmann, M., Hosli, I., Huber, M., Kaiser, L., Keiser, O., Klimkait, T., Kottanattu, L., Kouyos, R. D., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Marzolini, C., Metzner, K. J., Muller, N., Nicca, D., Paioni, P., Pantaleo, G., Perreau, M., Polli, C., Rauch, A., Rudin, C., Scherrer, A. U., Schmid, P., Speck, R., Stockle, M., Sultan-Beyer, L., Tarr, P., Thanh Lecompte, M., Trkola, A., Vernazza, P., Wagner, N., Wandeler, G., Weber, R., Yerly, S., Lyall, H., Butler, K., Doerholt, K., Doherty, C., Foster, C., Harrison, I., Kenny, J., Klein, N., Letting, G., Mcmaster, P., Murau, F., Nsangi, E., Prime, K., Riordan, A., Shackley, F., Shingadia, D., Storey, S., Tudor-Williams, G., Turkova, A., Welch, S., Cook, C., Dobson, D., Fairbrother, K., Prevost, M. L., Van Looy, N., Peters, H., Francis, K., Thrasyvoulou, L., Fidler, K., Bernatoniene, J., Manyika, F., Sharpe, G., Subramaniam, B., Hague, R., Price, V., Flynn, J., Cardoso, A., Abou - Rayyah, M., Yeadon, S., Segal, S., Hawkins, S., Dowie, M., Bandi, S., Percival, E., Eisenhut, M., Duncan, K., Anguvaa, L., Wren, L., Flood, T., Pickering, A., Murphy, C., Daniels, J., Lees, Y., Thompson, F., Williams, A., Williams, B., Pope, S., Libeschutz, S., Cliffe, L., Southall, S., Freeman, A., Freeman, H., Christie, S., Gordon, A., Rosie Hague, D., Clarke, L., Jones, L., Brown, L., Greenberg, M., Benson, C., Ibberson, L., Patel, S., Hancock, J., Sharland, M., Lyall, E. G. H., Seery, P., Kirkhope, N., Raghunanan, S., Callaghan, A., Bridgwood, A., Evans, J., Blake, E., Yannoulias, A., Department of Sciences for Woman and Child's Health, Florence University, Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Paediatric Infectious Diseases / Rheumatology / Immunology, Amsterdam institute for Infection and Immunity, Infectious diseases, AII - Infectious diseases, Amsterdam Reproduction & Development (AR&D), Medical Microbiology and Infection Prevention, Gastroenterology and Hepatology, Global Health, APH - Aging & Later Life, Biomedical Engineering and Physics, ACS - Atherosclerosis & ischemic syndromes, 1, Elizabeth Chappell, 2 3 4, Malte Kohns Vasconcelo, L Goodall 1, Ruth, 5, Luisa Galli, 6, Tessa Goetghebuer, 9 10, Antoni Noguera-Julian 7 8, C Rodrigues 2, Laura, Scherpbier 11, Henriette, Smit 12, Colette, 1 13 14, Alasdair Bamford, 1, Siobhan Crichton, Luisa Navarro 10 15 16 17, Marissa, T Ramos 18, Jose, Warszawski 19 20, Josiane, Spolou 21, Vana, 5, Elena Chiappini, 5, Elisabetta Venturini, Prata 22, Filipa, Kahlert 23, Christian, Marczynska 24, Magdalena, Marques 25, Laura, Naver 26, Lar, Thorne 14, Claire, M Gibb 1, Diana, Giaquinto 27, Carlo, 1, Ali Judd, 1, Intira Jeannie Collin, Pregnancy and Paediatric Infections Cohort Collaboration (EPPICC), European, Goodall, Ruth, Rodrigues, Laura, Duff, Charlotte, Gomezpena, Daniel, Jackson, Charlotte, Lundin, Rebecca, Mangiarini, Laura, Milanzi, Edith, Nardone, Alessandra, Hainaut, Marc, Van der Kelen, Evelyne, Delforge, Marc, Le Chenadec, Jerome, Ramos, Elisa, Dialla, Olivia, Wack, Thierry, Laurent, Corine, Ait Si Selmi, Lamya, Leymarie, Isabelle, Ait Benali, Fazia, Brossard, Maud, Boufassa, Leila, Floch-Tudal, Corinne, Firtion, Ghislaine, Hau, Isabelle, Chace, Anne, Bolot, Pascal, Blanche, Stéphane, Granier, Michèle, Labrune, Philippe, Lachassine, Eric, Dollfus, Catherine, Levine, Martine, Fourcade, Corinne, Heller-Roussin, Brigitte, Runel-Belliard, Camille, Tricoire, Joëlle, Monpoux, Fabrice, Chirouze, Catherine, Reliquet, Véronique, Brouard, Jacque, Kebaili, Kamila, Fialaire, Pascale, de Villeneuve, Arnaud, Lalande, Muriel, de Flandres, Jeanne, Mazingue, Françoise, Luisa Partisani, Maria, de Martino, Maurizio, Angelo Tovo, Pier, Gabiano, Clara, Carloni, Ine, Larovere, Domenico, Baldi, Francesco, Miniaci, Angela, Pession, Andrea, Badolato, Raffaele, Pantò, Grazia, Anastasio, Elisa, Montagnani, Carlotta, Bianchi, Leila, Allodi, Alessandra, Di Biagio, Antonio, Grignolo, Sara, Giacomet, Vania, Marchisio, Paola, Banderali, Giuseppe, Tagliabue, Claudia, Cellini, Monica, Bruzzese, Eugenia, DI COSTANZO, Pasquale, LO VECCHIO, Andrea, Donà, Daniele, Rampon, Osvalda, Romano, Amelia, Dodi, Icilio, Esposito, Susanna, Zuccaro, Valentina, Zanaboni, Domenico, Consolini, Rita, Bernardi, Stefania, Genovese, Orazio, Cristiano, Letizia, Mazza, Antonio, Garazzino, Silvia, Mignone, Federica, Silvestro, Erika, Portelli, Vincenzo, Pediatric surgery, Pediatrics, and Virology

Subjects
children, Europe, HIV, migrant, mortality, Adolescent, Child, Humans, Treatment Outcome, Viral Load, Anti-HIV Agents, HIV Infections, Transients and Migrants, medicine.medical_treatment, Human immunodeficiency virus (HIV), lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], medicine.disease_cause, 0302 clinical medicine, Medicine, Pharmacology (medical), 030212 general & internal medicine, health care economics and organizations, Health Policy, Hazard ratio, virus diseases, Immunosuppression, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, population characteristics, 0305 other medical science, Viral load, geographic locations, education, 03 medical and health sciences, Acquired immunodeficiency syndrome (AIDS), SDG 3 - Good Health and Well-being, 030505 public health, business.industry, Proportional hazards model, medicine.disease, Confidence interval, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Observational study, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Demography
Abstract

Contains fulltext : 249078.pdf (Publisher’s version ) (Open Access) OBJECTIVES: To assess the effect of migrant status on treatment outcomes among children living with HIV in Europe. METHODS: Children aged

Published
2022

21. Malignancies among children and young people with HIV in Western and Eastern Europe and Thailand the European Pregnancy and Paediatric Infections Cohort Collaboration (EPPICC) study group

Author

Chappell, E., Turkova, A., Goetghebuer, T., Jackson, C., Chiappini, E., Galli, L., Gingaras, C., Judd, A., Spoulou, V., Lisi, C., Ansone, S., Wolfs, T., Marczynska, M., Ene, L., Plotnikova, Y., Voronin, E., Samarina, A., Jourdain, G., Ngo-Giang-Huong, N., Fortuny, C., Navarro, M. L., Ramos, J. T., Naver, L., Crisinel, P. -A., Bailey, H., Malyuta, R., Volokha, A., Bamford, A., Crichton, S., Foster, C., Thorne, C., Collins, I. J., Giaquinto, C., Gibb, D. M., Critchton, S., Duff, C., Goodall, R., Gomezpena, D., Lundin, R., Mangiarini, L., Milanzi, E., Nardone, A., Hainaut, M., Van der Kelen, E., Delforge, M., de Martino, M., Tovo, P. A., Gabiano, C., Carloni, I., Larovere, D., Baldi, F., Miniaci, A., Pession, A., Badolato, R., Panto, G., Anastasio, E., Montagnani, C., Venturini, E., Bianchi, L., Allodi, A., Di Biagio, A., Grignolo, S., Giacomet, V., Marchisio, P., Banderali, G., Tagliabue, C., Cellini, M., Bruzzese, E., Di Costanzo, P., Lo Vecchio, A., Dona', D., Rampon, O., Romano, A., Dodi, I., Esposito, S., Zuccaro, V., Zanaboni, D., Consolini, R., Bernardi, S., Genovese, O., Cristiano, L., Mazza, A., Garazzino, S., Mignone, F., Silvestro, E., Portelli, V., Pajkrt, D., Scherpbier, H. J., Weijsenfeld, A. M., de Boer, C. G., Jurriaans, S., Back, N. K. T., Zaaijer, H. L., Berkhout, B., Cornelissen, M. T. E., Schinkel, C. J., Wolthers, K. C., Fraaij, P. L. A., van Rossum, A. M. C., Vermont, C. L., van der Knaap, L. C., Visser, E. G., Boucher, C. A. B., Koopmans, M. P. G., van Kampen, J. J. A., Pas, S. D., Henriet, S. S. V., van de Flier, M., van Aerde, K., Strik-Albers, R., Rahamat-Langendoen, J., Stelma, F. F., Scholvinck, E. H., de Groot-De Jonge, H., Niesters, H. G. M., van Leer-Buter, C. C., Knoester, M., Bont, L. J., Geelen, S. P. M., Wolfs, T. F. W., Nauta, N., Schuurman, R., Verduyn-Lunel, F., Wensing, A. M. J., Reiss, P., Zaheri, S., Bezemer, D. O., van Sighem, A. I., Smit, C., Wit, F. W. M. N., Hillebregt, M., de Jong, A., Woudstra, T., Bergsma, D., Grivell, S., Meijering, R., Raethke, M., Rutkens, T., de Groot, L., van den Akker, M., Bakker, Y., Bezemer, M., El Berkaoui, A., Geerlinks, J., Koops, J., Kruijne, E., Lodewijk, C., Lucas, E., van der Meer, R., Munjishvili, L., Paling, F., Peeck, B., Ree, C., Regtop, R., Ruijs, Y., van de Sande, L., Schoorl, M., Schnorr, P., Tuijn, E., Veenenberg, L., van der Vliet, S., Wisse, A., Witte, E. C., Tuk, B., Popielska, J., Pokorska-Spiewak, M., Oldakowska, A., Zawadka, K., Coupland, U., Doroba, M., Miloenko, M., Labutina, S., Soler-Palacin, P., Frick, M. A., Perez-Hoyos, S., Mur, A., Lopez, N., Mendez, M., Mayol, L., Vallmanya, T., Calavia, O., Garcia, L., Coll, M., Pineda, V., Rius, N., Rovira, N., Duenas, J., Noguera-Julian, A., Mellado, M. J., Escosa, L., Hortelano, M. G., Sainz, T., Gonzalez-Tome, M. I., Rojo, P., Blazquez, D., Prieto, L., Guillen, S., Saavedra, J., Santos, M., Munoz, M. A., Ruiz, B., Fernandez, C., Phee, M., de Ory, S. J., Alvarez, S., Roa, M. A., Beceiro, J., Martinez, J., Badillo, K., Apilanez, M., Pocheville, I., Garrote, E., Colino, E., Sirvent, J. G., Garzon, M., Roman, V., Montesdeoca, A., Mateo, M., Munoz, M. J., Angulo, R., Neth, O., Falcon, L., Terol, P., Santos, J. L., Moreno, D., Lendinez, F., Grande, A., Romero, F. J., Perez, C., Lillo, M., Losada, B., Herranz, M., Bustillo, M., Guerrero, C., Collado, P., Couceiro, J. A., Perez, A., Piqueras, A. I., Breton, R., Segarra, I., Gavilan, C., Jareno, E., Montesinos, E., Dapena, M., Alvarez, C., Andres, A. G., Marugan, V., Ochoa, C., Alfayate, S., Menasalvas, A. I., de Miguel, E., Soeria-Atmadja, S., Belfrage, E., Hagas, V., Aebi-Popp, K., Anagnostopoulos, A., Asner, S., Battegay, M., Baumann, M., Bernasconi, E., Boni, J., Braun, D. L., Bucher, H. C., Calmy, A., Cavassini, M., Ciuffi, A., Duppenthaler, A., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Francini, K., Furrer, H., Fux, C. A., Grawe, C., Gunthard, H. F., Haerry, D., Hasse, B., Hirsch, H. H., Hoffmann, M., Hosli, I., Huber, M., Kahlert, C. R., Kaiser, L., Keiser, O., Klimkait, T., Kottanattu, L., Kouyos, R. D., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Marzolini, C., Metzner, K. J., Muller, N., Nicca, D., Paioni, P., Pantaleo, G., Perreau, M., Polli, Ch., Rauch, A., Rudin, C., Scherrer, A. U., Schmid, P., Speck, R., Stockle, M., Tarr, P., Thanh Lecompte, M., Trkola, A., Vernazza, P., Wagner, N., Wandeler, G., Weber, R., Wyler, C. 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R., Clarke, L., Jones, L., Brown, L., Greenberg, M., Benson, C., Ibberson, L., Patel, S., Hancock, J., Sharland, M., Lyall, E. G. H., Seery, P., Kirkhope, N., Raghunanan, S., Callaghan, A., Bridgwood, A., Evans, J., Blake, E., Yannoulias, A., Chappell, E., Turkova, A., Goetghebuer, T., Jackson, C., Chiappini, E., Galli, L., Gingaras, C., Judd, A., Spoulou, V., Lisi, C., Ansone, S., Wolfs, T., Marczynska, M., Ene, L., Plotnikova, Y., Voronin, E., Samarina, A., Jourdain, G., Ngo-Giang-Huong, N., Fortuny, C., Navarro, M. L., Ramos, J. T., Naver, L., Crisinel, P. -A., Bailey, H., Malyuta, R., Volokha, A., Bamford, A., Crichton, S., Foster, C., Thorne, C., Collins, I. J., Giaquinto, C., Gibb, D. M., Critchton, S., Duff, C., Goodall, R., Gomezpena, D., Lundin, R., Mangiarini, L., Milanzi, E., Nardone, A., Hainaut, M., Van der Kelen, E., Delforge, M., de Martino, M., Tovo, P. A., Gabiano, C., Carloni, I., Larovere, D., Baldi, F., Miniaci, A., Pession, A., Badolato, R., Panto, G., Anastasio, E., Montagnani, C., Venturini, E., Bianchi, L., Allodi, A., Di Biagio, A., Grignolo, S., Giacomet, V., Marchisio, P., Banderali, G., Tagliabue, C., Cellini, M., Bruzzese, E., Di Costanzo, P., Lo Vecchio, A., Dona, D., Rampon, O., Romano, A., Dodi, I., Esposito, S., Zuccaro, V., Zanaboni, D., Consolini, R., Bernardi, S., Genovese, O., Cristiano, L., Mazza, A., Garazzino, S., Mignone, F., Silvestro, E., Portelli, V., Pajkrt, D., Scherpbier, H. J., Weijsenfeld, A. M., de Boer, C. G., Jurriaans, S., Back, N. K. T., Zaaijer, H. L., Berkhout, B., Cornelissen, M. T. E., Schinkel, C. J., Wolthers, K. C., Fraaij, P. L. A., van Rossum, A. M. C., Vermont, C. L., van der Knaap, L. C., Visser, E. G., Boucher, C. A. B., Koopmans, M. P. G., van Kampen, J. J. A., Pas, S. D., Henriet, S. S. V., van de Flier, M., van Aerde, K., Strik-Albers, R., Rahamat-Langendoen, J., Stelma, F. F., Scholvinck, E. H., de Groot-De Jonge, H., Niesters, H. G. M., van Leer-Buter, C. C., Knoester, M., Bont, L. J., Geelen, S. P. M., Wolfs, T. F. W., Nauta, N., Schuurman, R., Verduyn-Lunel, F., Wensing, A. M. J., Reiss, P., Zaheri, S., Bezemer, D. O., van Sighem, A. I., Smit, C., Wit, F. W. M. N., Hillebregt, M., de Jong, A., Woudstra, T., Bergsma, D., Grivell, S., Meijering, R., Raethke, M., Rutkens, T., de Groot, L., van den Akker, M., Bakker, Y., Bezemer, M., El Berkaoui, A., Geerlinks, J., Koops, J., Kruijne, E., Lodewijk, C., Lucas, E., van der Meer, R., Munjishvili, L., Paling, F., Peeck, B., Ree, C., Regtop, R., Ruijs, Y., van de Sande, L., Schoorl, M., Schnorr, P., Tuijn, E., Veenenberg, L., van der Vliet, S., Wisse, A., Witte, E. C., Tuk, B., Popielska, J., Pokorska-Spiewak, M., Oldakowska, A., Zawadka, K., Coupland, U., Doroba, M., Miloenko, M., Labutina, S., Soler-Palacin, P., Frick, M. A., Perez-Hoyos, S., Mur, A., Lopez, N., Mendez, M., Mayol, L., Vallmanya, T., Calavia, O., Garcia, L., Coll, M., Pineda, V., Rius, N., Rovira, N., Duenas, J., Noguera-Julian, A., Mellado, M. J., Escosa, L., Hortelano, M. G., Sainz, T., Gonzalez-Tome, M. I., Rojo, P., Blazquez, D., Prieto, L., Guillen, S., Saavedra, J., Santos, M., Munoz, M. A., Ruiz, B., Fernandez, C., Phee, M., de Ory, S. J., Alvarez, S., Roa, M. A., Beceiro, J., Martinez, J., Badillo, K., Apilanez, M., Pocheville, I., Garrote, E., Colino, E., Sirvent, J. G., Garzon, M., Roman, V., Montesdeoca, A., Mateo, M., Munoz, M. J., Angulo, R., Neth, O., Falcon, L., Terol, P., Santos, J. L., Moreno, D., Lendinez, F., Grande, A., Romero, F. J., Perez, C., Lillo, M., Losada, B., Herranz, M., Bustillo, M., Guerrero, C., Collado, P., Couceiro, J. A., Perez, A., Piqueras, A. I., Breton, R., Segarra, I., Gavilan, C., Jareno, E., Montesinos, E., Dapena, M., Alvarez, C., Andres, A. G., Marugan, V., Ochoa, C., Alfayate, S., Menasalvas, A. I., de Miguel, E., Soeria-Atmadja, S., Belfrage, E., Hagas, V., Aebi-Popp, K., Anagnostopoulos, A., Asner, S., Battegay, M., Baumann, M., Bernasconi, E., Boni, J., Braun, D. L., Bucher, H. C., Calmy, A., Cavassini, M., Ciuffi, A., Duppenthaler, A., Dollenmaier, G., Egger, M., Elzi, L., Fehr, J., Fellay, J., Francini, K., Furrer, H., Fux, C. A., Grawe, C., Gunthard, H. F., Haerry, D., Hasse, B., Hirsch, H. H., Hoffmann, M., Hosli, I., Huber, M., Kahlert, C. R., Kaiser, L., Keiser, O., Klimkait, T., Kottanattu, L., Kouyos, R. D., Kovari, H., Ledergerber, B., Martinetti, G., Martinez de Tejada, B., Marzolini, C., Metzner, K. J., Muller, N., Nicca, D., Paioni, P., Pantaleo, G., Perreau, M., Polli, Ch., Rauch, A., Rudin, C., Scherrer, A. U., Schmid, P., Speck, R., Stockle, M., Tarr, P., Thanh Lecompte, M., Trkola, A., Vernazza, P., Wagner, N., Wandeler, G., Weber, R., Wyler, C. A., Yerly, S., Wannarit, P., Techakunakorn, P., Hansudewechakul, R., Wanchaitanawong, V., Theansavettrakul, S., Nanta, S., Ngampiyaskul, C., Phanomcheong, S., Hongsiriwon, S., Karnchanamayul, W., Kwanchaipanich, R., Kanjanavanit, S., Kamonpakorn, N., Nantarukchaikul, M., Layangool, P., Mekmullica, J., Lucksanapisitkul, P., Watanayothin, S., Lertpienthum, N., Warachit, B., Hanpinitsak, S., Potchalongsin, S., Thanasiri, P., Krikajornkitti, S., Attavinijtrakarn, P., Srirojana, S., Bunjongpak, S., Puangsombat, A., Na-Rajsima, S., Ananpatharachai, P., Akarathum, N., Lawtongkum, W., Kheunjan, P., Suriyaboon, T., Saipanya, A., Than-In-At, K., Jaisieng, N., Suaysod, R., Chailoet, S., Naratee, N., Kawilapat, S., Kaleeva, T., Baryshnikova, Y., Soloha, S., Bashkatova, N., Raus, I., Glutshenko, O., Ruban, Z., Prymak, N., Kiseleva, G., Lyall, H., Butler, K., Doerholt, K., Doherty, C., Harrison, I., Kenny, J., Klein, N., Letting, G., Mcmaster, P., Murau, F., Nsangi, E., Prime, K., Riordan, A., Shackley, F., Shingadia, D., Storey, S., Tudor-Williams, G., Welch, S., Cook, C., Dobson, D., Fairbrother, K., Le Prevost, M., Van Looy, N., Peters, H., Francis, K., Thrasyvoulou, L., Fidler, K., Bernatoniene, J., Manyika, F., Sharpe, G., Subramaniam, B., Hague, R., Price, V., Flynn, J., Cardoso, A., Abou-Rayyah, M., Yeadon, S., Segal, S., Hawkins, S., Dowie, M., Bandi, S., Percival, E., Eisenhut, M., Duncan, K., Anguvaa, L., Wren, L., Flood, T., Pickering, A., Murphy, C., Daniels, J., Lees, Y., Thompson, F., Williams, A., Williams, B., Pope, S., Libeschutz, S., Cliffe, L., Southall, S., Freeman, A., Freeman, H., Christie, S., Gordon, A., Hague, D. R., Clarke, L., Jones, L., Brown, L., Greenberg, M., Benson, C., Ibberson, L., Patel, S., Hancock, J., Sharland, M., Lyall, E. G. H., Seery, P., Kirkhope, N., Raghunanan, S., Callaghan, A., Bridgwood, A., Evans, J., Blake, E., and Yannoulias, A.

Subjects
Adult, Male, Acquired Immunodeficiency Syndrome, Adolescent, Infant, HIV, HIV Infections, Eastern, Adolescents, Newborn, Thailand, Europe, malignancie, Neoplasms, malignancies, Humans, Children, Aged, Child, Europe, Eastern, Infant, Newborn
Abstract

Objectives: Investigate trends over time and predictors of malignancies among children and young people with HIV. Design: Pooled data from 17 cohorts in 15 countries across Europe and Thailand. Methods: Individuals diagnosed with HIV and presenting to paediatric care less than 18 years of age were included. Time at risk began at birth for children with documented vertically acquired HIV, and from first HIV-care visit for others. Children were followed until death, loss-to-follow-up, or last visit in paediatric or adult care (where data after transfer to adult care were available). Rates of reported malignancies were calculated overall and for AIDS-defining malignancies (ADM) and non-AIDS-defining malignancies (NADM) separately. Risk factors for any malignancy were explored using Poisson regression, and for mortality following a malignancy diagnosis using Cox regression. Results: Among 9632 individuals included, 140 (1.5%) were ever diagnosed with a malignancy, of which 112 (80%) were ADM. Overall, the rate of any malignancy was 1.18 per 1000 person-years; the rate of ADM decreased over time whereas the rate of NADM increased. Male sex, being from a European cohort, vertically acquired HIV, current severe immunosuppression, current viral load greater than 400 copies/ml, older age, and, for those not on treatment, earlier calendar year, were risk factors for a malignancy diagnosis. Fifty-eight (41%) individuals with a malignancy died, a median 2.4 months (IQR 0.6-8.8) after malignancy diagnosis. Conclusion: The rate of ADM has declined since widespread availability of combination ART, although of NADM, there was a small increase. Mortality following a malignancy was high, warranting further investigation.

Published
2021

22. Authors' reply

Author

Gibb, D M, Duong, T, and Tookey, P A

Published
2004

23. Low compliance with hepatocellular carcinoma screening guidelines in hepatitis B/C virus co-infected HIV patients with cirrhosis

Author

Willemse, S, Smit, C, Sogni, P, Sarcletti, M, Uberti-Foppa, C, Wittkop, L, Raben, D, D'Arminio Monforte, A, Dabis, F, Van Der Valk, M, Judd, A, Zangerle, R, Touloumi, G, Warszawski, J, Meyer, L, Murielle, M, Ghosn, J, Leport, C, Reiss, P, Wit, F, Prins, M, Bucher, H, Gibb, D, Fatkenheuer, G, Obel, N, Thorne, C, Mocroft, A, Kirk, O, Stephan, C, Perez-Hoyos, S, Hamouda, O, Clinsurv, G, Bartmeyer, B, Chkhartishvili, N, Noguera-Julian, A, Antinori, A, Brockmeyer, N, Prieto, L, Pablo, R, Soriano-Arandes, A, Battegay, M, Kouyos, R, Mussini, C, Tookey, P, Casabona, J, Miro, J, Castagna, A, Konopnick, D, Goetghebuer, T, Sonnerborg, A, Torti, C, Sabin, C, Teira, R, Garrido, M, Haerry, D, Stephane, D, Jose, M, Costagliola, D, Raffaele, S, Julia, D, Chene, G, Barger, D, Schwimmer, C, Termote, M, Campbell, M, Frederiksen, C, Friis-Moller, N, Kjaer, J, Bohlius, J, Bouteloup, V, Cozzi-Lepri, A, Davies, M, Dorrucci, M, Dunn, D, Egger, M, Furrer, H, Guiguet, M, Grabar, S, Lambotte, O, Leroy, V, Lodi, S, Matheron, S, Monge, S, Nakagawa, F, Paredes, R, Phillips, A, Puoti, M, Rohner, E, Schomaker, M, Sterne, J, Thiebaut, R, Willemse S., Smit C., Sogni P., Sarcletti M., Uberti-Foppa C., Wittkop L., Raben D., D'Arminio Monforte A., Dabis F., Van Der Valk M., Judd A., Zangerle R., Touloumi G., Warszawski J., Meyer L., Murielle M., Ghosn J., Leport C., Reiss P., Wit F., Prins M., Bucher H., Gibb D., Fatkenheuer G., Obel N., Thorne C., Mocroft A., Kirk O., Stephan C., Perez-Hoyos S., Hamouda O., ClinSurv G., Bartmeyer B., Chkhartishvili N., Noguera-Julian A., Antinori A., Brockmeyer N., Prieto L., Pablo R., Soriano-Arandes A., Battegay M., Kouyos R., Mussini C., Tookey P., Casabona J., Miro J. M., Castagna A., Konopnick D., Goetghebuer T., Sonnerborg A., Torti C., Sabin C., Teira R., Garrido M., Haerry D., Stephane D., Jose M., Costagliola D., Raffaele S., Julia D., Chene G., Barger D., Schwimmer C., Termote M., Campbell M., Frederiksen C. M., Friis-Moller N., Kjaer J., Bohlius J., Bouteloup V., Cozzi-Lepri A., Davies M. -A., Dorrucci M., Dunn D., Egger M., Furrer H., Guiguet M., Grabar S., Lambotte O., Leroy V., Lodi S., Matheron S., Monge S., Nakagawa F., Paredes R., Phillips A., Puoti M., Rohner E., Schomaker M., Sterne J., Thiebaut R., Willemse, S, Smit, C, Sogni, P, Sarcletti, M, Uberti-Foppa, C, Wittkop, L, Raben, D, D'Arminio Monforte, A, Dabis, F, Van Der Valk, M, Judd, A, Zangerle, R, Touloumi, G, Warszawski, J, Meyer, L, Murielle, M, Ghosn, J, Leport, C, Reiss, P, Wit, F, Prins, M, Bucher, H, Gibb, D, Fatkenheuer, G, Obel, N, Thorne, C, Mocroft, A, Kirk, O, Stephan, C, Perez-Hoyos, S, Hamouda, O, Clinsurv, G, Bartmeyer, B, Chkhartishvili, N, Noguera-Julian, A, Antinori, A, Brockmeyer, N, Prieto, L, Pablo, R, Soriano-Arandes, A, Battegay, M, Kouyos, R, Mussini, C, Tookey, P, Casabona, J, Miro, J, Castagna, A, Konopnick, D, Goetghebuer, T, Sonnerborg, A, Torti, C, Sabin, C, Teira, R, Garrido, M, Haerry, D, Stephane, D, Jose, M, Costagliola, D, Raffaele, S, Julia, D, Chene, G, Barger, D, Schwimmer, C, Termote, M, Campbell, M, Frederiksen, C, Friis-Moller, N, Kjaer, J, Bohlius, J, Bouteloup, V, Cozzi-Lepri, A, Davies, M, Dorrucci, M, Dunn, D, Egger, M, Furrer, H, Guiguet, M, Grabar, S, Lambotte, O, Leroy, V, Lodi, S, Matheron, S, Monge, S, Nakagawa, F, Paredes, R, Phillips, A, Puoti, M, Rohner, E, Schomaker, M, Sterne, J, Thiebaut, R, Willemse S., Smit C., Sogni P., Sarcletti M., Uberti-Foppa C., Wittkop L., Raben D., D'Arminio Monforte A., Dabis F., Van Der Valk M., Judd A., Zangerle R., Touloumi G., Warszawski J., Meyer L., Murielle M., Ghosn J., Leport C., Reiss P., Wit F., Prins M., Bucher H., Gibb D., Fatkenheuer G., Obel N., Thorne C., Mocroft A., Kirk O., Stephan C., Perez-Hoyos S., Hamouda O., ClinSurv G., Bartmeyer B., Chkhartishvili N., Noguera-Julian A., Antinori A., Brockmeyer N., Prieto L., Pablo R., Soriano-Arandes A., Battegay M., Kouyos R., Mussini C., Tookey P., Casabona J., Miro J. M., Castagna A., Konopnick D., Goetghebuer T., Sonnerborg A., Torti C., Sabin C., Teira R., Garrido M., Haerry D., Stephane D., Jose M., Costagliola D., Raffaele S., Julia D., Chene G., Barger D., Schwimmer C., Termote M., Campbell M., Frederiksen C. M., Friis-Moller N., Kjaer J., Bohlius J., Bouteloup V., Cozzi-Lepri A., Davies M. -A., Dorrucci M., Dunn D., Egger M., Furrer H., Guiguet M., Grabar S., Lambotte O., Leroy V., Lodi S., Matheron S., Monge S., Nakagawa F., Paredes R., Phillips A., Puoti M., Rohner E., Schomaker M., Sterne J., and Thiebaut R.

Published
2019

24. Low compliance with hepatocellular carcinoma screening guidelines in hepatitis B/C virus co-infected HIV patients with cirrhosis

Author

Willemse, S., Smit, C., Sogni, P., Sarcletti, M., Uberti-Foppa, C., Wittkop, L., Raben, D., D'Arminio Monforte, A., Dabis, F., Van Der Valk, M., Judd, A., Zangerle, R., Touloumi, G., Warszawski, J., Meyer, L., Murielle, M., Ghosn, J., Leport, C., Reiss, P., Wit, F., Prins, M., Bucher, H., Gibb, D., Fatkenheuer, G., Obel, N., Thorne, C., Mocroft, A., Kirk, O., Stephan, C., Perez-Hoyos, S., Hamouda, O., Clinsurv, G., Bartmeyer, B., Chkhartishvili, N., Noguera-Julian, A., Antinori, A., Brockmeyer, N., Prieto, L., Pablo, R., Soriano-Arandes, A., Battegay, M., Kouyos, R., Mussini, C., Tookey, P., Casabona, J., Miro, J. M., Castagna, A., Konopnick, D., Goetghebuer, T., Sonnerborg, A., Torti, C., Sabin, C., Teira, R., Garrido, M., Haerry, D., Stephane, D., Jose, M., Costagliola, D., Raffaele, S., Julia, D., Chene, G., Barger, D., Schwimmer, C., Termote, M., Campbell, M., Frederiksen, C. M., Friis-Moller, N., Kjaer, J., Bohlius, J., Bouteloup, V., Cozzi-Lepri, A., Davies, M. -A., Dorrucci, M., Dunn, D., Egger, M., Furrer, H., Guiguet, M., Grabar, S., Lambotte, O., Leroy, V., Lodi, S., Matheron, S., Monge, S., Nakagawa, F., Paredes, R., Phillips, A., Puoti, M., Rohner, E., Schomaker, M., Sterne, J., Thiebaut, R., Willemse, S., Smit, C., Sogni, P., Sarcletti, M., Uberti-Foppa, C., Wittkop, L., Raben, D., D'Arminio Monforte, A., Dabis, F., Van Der Valk, M., Judd, A., Zangerle, R., Touloumi, G., Warszawski, J., Meyer, L., Murielle, M., Ghosn, J., Leport, C., Reiss, P., Wit, F., Prins, M., Bucher, H., Gibb, D., Fatkenheuer, G., Obel, N., Thorne, C., Mocroft, A., Kirk, O., Stephan, C., Perez-Hoyos, S., Hamouda, O., Clinsurv, G., Bartmeyer, B., Chkhartishvili, N., Noguera-Julian, A., Antinori, A., Brockmeyer, N., Prieto, L., Pablo, R., Soriano-Arandes, A., Battegay, M., Kouyos, R., Mussini, C., Tookey, P., Casabona, J., Miro, J. M., Castagna, A., Konopnick, D., Goetghebuer, T., Sonnerborg, A., Torti, C., Sabin, C., Teira, R., Garrido, M., Haerry, D., Stephane, D., Jose, M., Costagliola, D., Raffaele, S., Julia, D., Chene, G., Barger, D., Schwimmer, C., Termote, M., Campbell, M., Frederiksen, C. M., Friis-Moller, N., Kjaer, J., Bohlius, J., Bouteloup, V., Cozzi-Lepri, A., Davies, M. -A., Dorrucci, M., Dunn, D., Egger, M., Furrer, H., Guiguet, M., Grabar, S., Lambotte, O., Leroy, V., Lodi, S., Matheron, S., Monge, S., Nakagawa, F., Paredes, R., Phillips, A., Puoti, M., Rohner, E., Schomaker, M., Sterne, J., Thiebaut, R., Willemse, S, Smit, C, Sogni, P, Sarcletti, M, Uberti-Foppa, C, Wittkop, L, Raben, D, D'Arminio Monforte, A, Dabis, F, Van Der Valk, M, Judd, A, Zangerle, R, Touloumi, G, Warszawski, J, Meyer, L, Murielle, M, Ghosn, J, Leport, C, Reiss, P, Wit, F, Prins, M, Bucher, H, Gibb, D, Fatkenheuer, G, Obel, N, Thorne, C, Mocroft, A, Kirk, O, Stephan, C, Perez-Hoyos, S, Hamouda, O, Clinsurv, G, Bartmeyer, B, Chkhartishvili, N, Noguera-Julian, A, Antinori, A, Brockmeyer, N, Prieto, L, Pablo, R, Soriano-Arandes, A, Battegay, M, Kouyos, R, Mussini, C, Tookey, P, Casabona, J, Miro, J, Castagna, A, Konopnick, D, Goetghebuer, T, Sonnerborg, A, Torti, C, Sabin, C, Teira, R, Garrido, M, Haerry, D, Stephane, D, Jose, M, Costagliola, D, Raffaele, S, Julia, D, Chene, G, Barger, D, Schwimmer, C, Termote, M, Campbell, M, Frederiksen, C, Friis-Moller, N, Kjaer, J, Bohlius, J, Bouteloup, V, Cozzi-Lepri, A, Davies, M, Dorrucci, M, Dunn, D, Egger, M, Furrer, H, Guiguet, M, Grabar, S, Lambotte, O, Leroy, V, Lodi, S, Matheron, S, Monge, S, Nakagawa, F, Paredes, R, Phillips, A, Puoti, M, Rohner, E, Schomaker, M, Sterne, J, Thiebaut, R, Infectious diseases, AII - Infectious diseases, Global Health, APH - Aging & Later Life, APH - Global Health, APH - Digital Health, and APH - Personalized Medicine

Subjects
Liver Cirrhosis, Male, Cirrhosis, co‐infection, medicine.disease_cause, 0302 clinical medicine, 80 and over, Mass Screening, 030212 general & internal medicine, Chronic, guideline adherence, Aged, 80 and over, cancer screening, chronic viral hepatitis, co-infection, hepatocellular carcinoma, hepatocellular carcinoma screening, human immunodeficiency virus, liver cirrhosis, Adolescent, Adult, Aged, Carcinoma, Hepatocellular, Coinfection, Female, Guideline Adherence, Hepatitis B, Chronic, Hepatitis C, Chronic, Humans, Liver Neoplasms, Middle Aged, Young Adult, medicine.diagnostic_test, chronic viral hepatiti, virus diseases, Hepatitis C, Hepatitis B, 3. Good health, Infectious Diseases, Hepatocellular carcinoma, Liver biopsy, 030211 gastroenterology & hepatology, medicine.medical_specialty, Hepatitis C virus, Short Communication, Short Communications, 03 medical and health sciences, Virology, Internal medicine, medicine, Mass screening, Hepatitis B virus, Hepatology, business.industry, human immunodeficiency viru, Carcinoma, Hepatocellular, medicine.disease, digestive system diseases, business
Abstract

The incidence of hepatocellular carcinoma (HCC) in patients co-infected with HIV and hepatitis B virus (HBV) or hepatitis C virus (HCV) is increasing. In patients with cirrhosis, guidelines recommend HCC screening every 6 months. We assessed compliance with HCC screening guidelines in cirrhotic HBV/HCV-HIV-co-infected patients. HBV/HCV-HIV-co-infected patients with cirrhosis were enrolled from 4 European prospective cohorts participating in the COHERE collaboration, followed from 1 January 2005-1 January 2015. Assessment of liver cirrhosis was based on clinical diagnosis and liver biopsy or Fibroscan. Compliance with HCC screening guidelines was defined as one ultrasound every 6 months. Generalized estimating equation models adjusted for repeated measurements were fitted to determine predictors of low compliance. Different sensitivity analyses were performed and validation of the data was carried out by randomly checking 10% of each cohort's data. 646 HIV-patients with the diagnosis of cirrhosis were included: 518 (80%) HCV-, 85 (13%) HBV- and 43 (7%) HBV/HCV-co-infected. Median age at cirrhosis diagnosis was 44 years, median follow-up time since diagnosis was 5.3 years. Screening

Published
2019

25. Withholding Primary Pneumocystis Pneumonia Prophylaxis in Virologically Suppressed Patients With Human Immunodeficiency Virus: An Emulation of a Pragmatic Trial in COHERE

Author

Atkinson A., Zwahlen M., Barger D., D'arminio Monforte A., De Wit S., Ghosn J., Girardi E., Svedhem V., Morlat P., Mussini C., Noguera-Julian A., Stephan C., Touloumi G., Kirk O., Mocroft A., Reiss P., Miro J. M., Carpenter J. R., Furrer H., Judd A., Zangerle R., Warszawski J., Meyer L., Dabis F., Krause M. M., Leport C., Wittkop L., Wit F., Prins M., Bucher H., Gibb D., Fatkenheuer G., Del Amo J., Obel N., Thorne C., Perez-Hoyos S., Hamouda O., Bartmeyer B., Chkhartishvili N., Antinori A., Brockmeyer N., Prieto L., Rojo Conejo P., Soriano-Arandes A., Battegay M., Kouyos R., Casabona J., M. Miro J., Castagna A., Konopnick D., Goetghebuer T., Sonnerborg A., Torti C., Sabin C., Teira R., Garrido M., Haerry D., Costagliola D., D'arminio-Monforte A., Raben D., Chene G., Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Agence Nationale de Recherches sur le Sida et les Hépatites Virales, European Project: 260694,EC:FP7:HEALTH,FP7-HEALTH-2010-single-stage,EUROCOORD(2011), Atkinson, A., Zwahlen, M., Barger, D., D'arminio Monforte, A., De Wit, S., Ghosn, J., Girardi, E., Svedhem, V., Morlat, P., Mussini, C., Noguera-Julian, A., Stephan, C., Touloumi, G., Kirk, O., Mocroft, A., Reiss, P., Miro, J. M., Carpenter, J. R., Furrer, H., Judd, A., Zangerle, R., Warszawski, J., Meyer, L., Dabis, F., Krause, M. M., Leport, C., Wittkop, L., Wit, F., Prins, M., Bucher, H., Gibb, D., Fatkenheuer, G., Del Amo, J., Obel, N., Thorne, C., Perez-Hoyos, S., Hamouda, O., Bartmeyer, B., Chkhartishvili, N., Antinori, A., Brockmeyer, N., Prieto, L., Rojo Conejo, P., Soriano-Arandes, A., Battegay, M., Kouyos, R., Casabona, J., M. Miro, J., Castagna, A., Konopnick, D., Goetghebuer, T., Sonnerborg, A., Torti, C., Sabin, C., Teira, R., Garrido, M., Haerry, D., Costagliola, D., D'arminio-Monforte, A., Raben, D., Chene, G., Global Health, Infectious diseases, AII - Infectious diseases, and APH - Aging & Later Life

Subjects
Microbiology (medical), Microbiologie et protistologie [parasitologie hum. et anim.], medicine.medical_specialty, Human immunodeficiency virus (HIV), HIV Infections, Logistic regression, Pneumocystis pneumonia, medicine.disease_cause, 01 natural sciences, law.invention, 010104 statistics & probability, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, Pragmatic Clinical Trials as Topic, medicine, Humans, 030212 general & internal medicine, 0101 mathematics, Pathologie maladies infectieuses, AIDS-Related Opportunistic Infections, human immunodeficiency virus, business.industry, Pneumonia, Pneumocystis, pneumocystis pneumonia, Hazard ratio, HIV, medicine.disease, Confidence interval, 3. Good health, CD4 Lymphocyte Count, Microbiologie et protistologie [entomologie,phytoparasitolog.], Major Articles and Commentaries, Infectious Diseases, AcademicSubjects/MED00290, HIV-RNA, Censoring (clinical trials), [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Observational study, prophylaxis, business, Microbiologie et protistologie [bacteriol.virolog.mycolog.]
Abstract

BACKGROUND: Using data from the COHERE collaboration, we investigated whether primary prophylaxis for pneumocystis pneumonia (PcP) might be withheld in all patients on antiretroviral therapy (ART) with suppressed plasma human immunodeficiency virus (HIV) RNA (≤400 copies/mL), irrespective of CD4 count. METHODS: We implemented an established causal inference approach whereby observational data are used to emulate a randomized trial. Patients taking PcP prophylaxis were eligible for the emulated trial if their CD4 count was ≤200 cells/µL in line with existing recommendations. We compared the following 2 strategies for stopping prophylaxis: (1) when CD4 count was >200 cells/µL for >3 months or (2) when the patient was virologically suppressed (2 consecutive HIV RNA ≤400 copies/mL). Patients were artificially censored if they did not comply with these stopping rules. We estimated the risk of primary PcP in patients on ART, using the hazard ratio (HR) to compare the stopping strategies by fitting a pooled logistic model, including inverse probability weights to adjust for the selection bias introduced by the artificial censoring. RESULTS: A total of 4813 patients (10 324 person-years) complied with eligibility conditions for the emulated trial. With primary PcP diagnosis as an endpoint, the adjusted HR (aHR) indicated a slightly lower, but not statistically significant, different risk for the strategy based on viral suppression alone compared with the existing guidelines (aHR, 8; 95% confidence interval, 6-1.1; P = .2). CONCLUSIONS: This study suggests that primary PcP prophylaxis might be safely withheld in confirmed virologically suppressed patients on ART, regardless of their CD4 count., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2020

27. Incidence and predictors of hospital readmission in children presenting with severe anaemia in Uganda and Malawi: a secondary analysis of TRACT trial data

Author

Connon, Roisin, George, Elizabeth C., Olupot-Olupot, Peter, Kiguli, Sarah, Chagaluka, George, Alaroker, Florence, Opoka, Robert O., Mpoya, Ayub, Walsh, Kevin, Engoru, Charles, Nteziyaremye, Julius, Mallewa, Macpherson, Kennedy, Neil, Nakuya, Margaret, Namayanja, Cate, Nabawanuka, Eva, Sennyondo, Tonny, Amorut, Denis, Williams Musika, C., Bates, Imelda, Boele van Hensbroek, M., Evans, Jennifer A., Uyoga, Sophie, Williams, Thomas N., Frost, Gary, Gibb, Diana M., Maitland, Kathryn, Walker, A. Sarah, Kiguli, S., Opoka, R. O., Nabawanuka, E., Kayaga, J., Kadama, E., Mbwali, I., Nuwabaine, L., Nakikwaku, R., Nsubuga, J., Mpande, K., Adoo, R., Ouma, O., Adia, N. K., Olupot-Olupot, P., Nteziyaremye, J., Namanyanga, C., Passi, G., Sennyondo, T., Adong, R., Okalebo, C. B., Atimango, E., Mwamula, S., Kapsindet, J., Muhindo, G. Kiluli R., Thembo, G. Masifa N., Odong, G., Engoru, C., Aloroker, F., Nakuya, M., Amorut, D., Ariima, M., Itipe, M., Atim, M. G., Abeno, M., Amede, B., Olupot, M., Okwi, S., Kulume, M. G., Among, G., Onyas, P., Achipa, E. D., Maitland, K., Mpoya, A., Maitha, P., Uyoga, S., Williams, T. N., Macharia, A., Mallewa, M., Chagaluka, G., Chimalizeni, Y., Kennedy, N., Kumwenda, F., Nkosi, E., Sochera, T., Malenga, A., Gushu, B., Phiri, T., Chisale, A., Mitole, N., Chokani, E., Munthali, A., Frost, G., Walsheto, K., Gibb, D. M., George, E. C., Thomason, M., Baptiste, D., McCabe, L., Walker, A. S., Ali, A., Khamis, K., Madula, M., Abongo, G., Heydermann, R., Bates, I., Urban, B., Kyomuhendo, F., Nakalanzi, S., Chabuka, J., Mkandawire, N., Evans, J. A., Fitzgerald, F., Molyneux, E., Murphy, I. Lubega M., Kazembe, P., Crawley, J., Peto, T., Musoke, P., Todd, J., Mirembe, G., and Tenu, F.

Subjects
wh_155, ws_300, wa_395, wa_320
Abstract

Background: Severe anaemia (haemoglobin < 6 g/dL) is a leading cause of recurrent hospitalisation in African children. We investigated predictors of readmission in children hospitalised with severe anaemia in the TRACT trial (ISRCTN84086586) in order to identify potential future interventions.\ud Methods: Secondary analyses of the trial examined 3894 children from Uganda and Malawi surviving a hospital episode of severe anaemia. Predictors of all-cause readmission within 180 days of discharge were identified using multivariable regression with death as a competing risk. Groups of children with similar characteristics were identified using hierarchical clustering.\ud Results: Of the 3894 survivors 682 (18%) were readmitted; 403 (10%) had ≥2 re-admissions over 180 days. Three main causes of readmission were identified: severe anaemia (n = 456), malaria (n = 252) and haemoglobinuria/dark urine syndrome (n = 165). Overall, factors increasing risk of readmission included HIV-infection (hazard ratio 2.48\ud (95% CI 1.63–3.78), p < 0.001); ≥2 hospital admissions in the preceding 12 months (1.44(1.19–1.74), p < 0.001); history of transfusion (1.48(1.13–1.93), p = 0.005); and missing ≥1 trial medication dose (proxy for care quality) (1.43 (1.21–1.69), p < 0.001). Children with uncomplicated severe anaemia (Hb 4-6 g/dL and no severity features),\ud who never received a transfusion (per trial protocol) during the initial admission had a substantially lower risk of readmission (0.67(0.47–0.96), p = 0.04). Malaria (among children with no prior history of transfusion) (0.60(0.47–0.76), p < 0.001); younger-age (1.07 (1.03–1.10) per 1 year younger, p < 0.001) and known sickle cell disease (0.62(0.46–0.82), p = 0.001) also decreased risk of readmission. For anaemia re-admissions, gross splenomegaly and enlarged spleen increased risk by 1.73(1.23–2.44) and 1.46(1.18–1.82) respectively compared to no splenomegaly.\ud Clustering identified four groups of children with readmission rates from 14 to 20%. The cluster with the highest readmission rate was characterised by very low haemoglobin (mean 3.6 g/dL). Sickle Cell Disease (SCD) predominated in two clusters associated with chronic repeated admissions or severe, acute presentations in largely undiagnosed SCD. The final cluster had high rates of malaria (78%), severity signs and very low platelet count, consistent with acute severe\ud malaria.\ud Conclusions: Younger age, HIV infection and history of previous hospital admissions predicted increased risk of readmission. However, no obvious clinical factors for intervention were identified. As missing medication doses was highly predictive, attention to care related factors may be important.\ud Trial registration: ISRCTN ISRCTN84086586.\ud Keywords: Severe anaemia, Readmission

Published
2021

28. CD4/CD8 Ratio and the Risk of Kaposi Sarcoma or Non-Hodgkin Lymphoma in the Context of Efficiently Treated Human Immunodeficiency Virus (HIV) Infection: A Collaborative Analysis of 20 European Cohort Studies

Author

Caby, F., Guiguet, M., Weiss, L., Winston, A. d., Miro, J. M., Konopnicki, D., Le Moing, V., Bonnet, F. h., Reiss, P., Mussini, C., Poizot-Martin, I., Taylor, N. l., Skoutelis, A., Meyer, L., Goujard, C., Bartmeyer, B., Boesecke, C., Antinori, A., Quiros-Roldan, E., Wittkop, L., Frederiksen, C., Castagna, A., Thurnheer, M. C., Svedhem, V., Jose, S., Costagliola, D., Mary-Krause, M., Grabar, S., Judd, A., Zangerle, R., Touloumi, G., Warszawski, J., Dabis, F., Krause, M. M., Ghosn, J., Leport, C., Wit, F., Prins, M., Bucher, H., Gibb, D., Fätkenheuer, G., Del Amo, J., Obel, N., Thorne, C., Mocroft, A., Kirk, O., Stephan, C., Pérez-Hoyos, S., Hamouda, O., Chkhartishvili, N., Noguera-Julian, A., Monforte, A. D., Brockmeyer, N., Prieto, L., Conejo, P. R., Soriano-Arandes, A., Battegay, M., Kouyos, R., Casabona, J., Miró, J. M., Konopnick, D., Goetghebuer, T., Sönnerborg, A., Torti, C., Sabin, C., Teira, R., Garrido, M., Haerry, D., Statistics In System biology and Translational Medicine (SISTM), Inria Bordeaux - Sud-Ouest, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)- Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Victor Dupouy, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Hôpital Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imperial College London, University of Barcelona, Université libre de Bruxelles (ULB), CHU Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], University of Amsterdam [Amsterdam] (UvA), Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Evangelismos Athens General Hospital, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Hôpital Bicêtre, Robert Koch Institute [Berlin] (RKI), University Hospital Bonn, National Institute for Infectious Diseases 'Lazzaro Spallanzani', Università degli Studi di Brescia = University of Brescia (UniBs), Team MORPH3EUS (INSERM U1219 - UB - ISPED), University of Copenhagen = Københavns Universitet (UCPH), IRCCS Ospedale San Raffaele [Milan, Italy], Bern University Hospital [Berne] (Inselspital), Karolinska Institutet [Stockholm], Public Health England [London], Hôpital Cochin [AP-HP], Agence Nationale de Recherches sur le Sida et les Hépatites Virales, (CD4/CD8 ratio and cancer risk) project Working Group for the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) in EuroCoord: Ali Judd, Robert Zangerle, Giota Touloumi, Josiane Warszawski, Laurence Meyer, François Dabis, Murielle Mary Krause, Jade Ghosn, Catherine Leport, Linda Wittkop, Peter Reiss, Ferdinand Wit, Maria Prins, Heiner Bucher, Diana Gibb, Gerd Fätkenheuer, Julia Del Amo, Niels Obel, Claire Thorne, Amanda Mocroft, Ole Kirk, Christoph Stephan, Santiago Pérez-Hoyos, Osamah Hamouda, Barbara Bartmeyer, Nikoloz Chkhartishvili, Antoni Noguera-Julian, Andrea Antinori, Antonella d'Arminio Monforte, Norbert Brockmeyer, Luis Prieto, Pablo Rojo Conejo, Antoni Soriano-Arandes, Manuel Battegay, Roger Kouyos, Cristina Mussini, Jordi Casabona, Jose M Miró, Antonella Castagna, Deborah Konopnick, Tessa Goetghebuer, Anders Sönnerborg, Carlo Torti, Caroline Sabin, Ramon Teira, Myriam Garrido, David Haerry, European Project: 287519, European Project: 260694,EC:FP7:HEALTH,FP7-HEALTH-2010-single-stage,EUROCOORD(2011), Admin, Oskar, European Union Seventh Framework Programme - 287519 - INCOMING, European Network of HIV/AIDS Cohort Studies to Coordinate at European and International Level Clinical Research on HIV/AIDS - EUROCOORD - - EC:FP7:HEALTH2011-01-01 - 2015-12-31 - 260694 - VALID, Caby, Fabienne, Guiguet, Marguerite, Weiss, Laurence, Winston, Alan, Miro, Jose M, Konopnicki, Deborah, Le Moing, Vincent, Bonnet, Fabrice, Reiss, Peter, Mussini, Cristina, Poizot-Martin, Isabelle, Taylor, Ninon, Skoutelis, Athanasio, Meyer, Laurence, Goujard, Cécile, Bartmeyer, Barbara, Boesecke, Christoph, Antinori, Andrea, Quiros-Roldan, Eugenia, Wittkop, Linda, Frederiksen, Casper, Castagna, Antonella, Thurnheer, Maria Christine, Svedhem, Veronica, Jose, Sophie, Costagliola, Dominique, Mary-Krause, Murielle, Grabar, Sophie, Global Health, Infectious diseases, AII - Infectious diseases, and APH - Aging & Later Life

Subjects
CD4/CD8 ratio, CD8 T-cells, Kaposi sarcoma, efficient cART, non-Hodgkin lymphoma, 0301 basic medicine, Microbiology (medical), Lymphoma, [SDV]Life Sciences [q-bio], 030106 microbiology, CD4-CD8 Ratio, Non-Hodgkin, HIV Infections, Kaposi, Efficient cART, Drug resistance, HIV superinfection, CD8-Positive T-Lymphocytes, medicine.disease_cause, Men who have sex with men, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, CD4 Lymphocyte Count, HIV, Humans, Incidence, Risk Factors, Lymphoma, Non-Hodgkin, Sarcoma, Kaposi, immune system diseases, Medicine, 030212 general & internal medicine, Non-Hodgkin lymphoma, Transmission (medicine), business.industry, Sarcoma, Resistance mutation, 3. Good health, Infectious Diseases, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Superinfection, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Viral load, HIV drug resistance, Demography
Abstract

BackgroundA persistently low CD4/CD8 ratio has been reported to inversely correlate with the risk of non-AIDS defining cancer in people living with human immunodeficiency virus (HIV; PLWH) efficiently treated by combination antiretroviral therapy (cART). We evaluated the impact of the CD4/CD8 ratio on the risk of Kaposi sarcoma (KS) or non-Hodgkin lymphoma (NHL), still among the most frequent cancers in treated PLWH.MethodsPLWH from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) were included if they achieved virological control (viral load ≤ 500 copies/mL) within 9 months following cART and without previous KS/LNH diagnosis. Cox models were used to identify factors associated with KS or NHL risk, in all participants and those with CD4 ≥ 500/mm3 at virological control. We analyzed the CD4/CD8 ratio, CD4 count and CD8 count as time-dependent variables, using spline transformations.ResultsWe included 56 708 PLWH, enrolled between 2000 and 2014. At virological control, the median (interquartile range [IQR]) CD4 count, CD8 count, and CD4/CD8 ratio were 414 (296–552)/mm3, 936 (670–1304)/mm3, and 0.43 (0.28–0.65), respectively. Overall, 221 KS and 187 NHL were diagnosed 9 (2–37) and 18 (7–42) months after virological control. Low CD4/CD8 ratios were associated with KS risk (hazard ratio [HR] = 2.02 [95% confidence interval {CI } = 1.23–3.31]) when comparing CD4/CD8 = 0.3 to CD4/CD8 = 1) but not with NHL risk. High CD8 counts were associated with higher NHL risk (HR = 3.14 [95% CI = 1.58–6.22]) when comparing CD8 = 3000/mm3 to CD8 = 1000/mm3). Similar results with increased associations were found in PLWH with CD4 ≥ 500/mm3 at virological control (HR = 3.27 [95% CI = 1.60–6.56] for KS; HR = 5.28 [95% CI = 2.17–12.83] for NHL).ConclusionsLow CD4/CD8 ratios and high CD8 counts despite effective cART were associated with increased KS/NHL risks respectively, especially when CD4 ≥ 500/mm3.

Published
2021

29. Pharmacokinetics and pharmacodynamics of azithromycin in severe malaria bacterial co-infection in African children (TABS-PKPD): a protocol for a Phase II randomised controlled trial [version 1; peer review: 1 approved with reservations]

Author

Olupot-Olupot, P, Okiror, W, Mnjalla, H, Muhindo, R, Uyoga, S, Mpoya, A, Williams, T, TerHeine, R, Burger, D, Urban, B, Connon, R, George, E, Gibb, D, Walker, S, and Maitland, K

Abstract

Background: African children with severe malaria are susceptible to Gram-negative bacterial co-infection, largely non-typhoidal Salmonellae, leading to a substantially higher rates of in-hospital and post-discharge mortality than those without bacteraemia. Current evidence for treating co-infection is lacking, and there is no consensus on the dosage or length of treatment required. We therefore aimed to establish the appropriate dose of oral dispersible azithromycin as an antimicrobial treatment for children with severe malaria and to investigate whether antibiotics can be targeted to those at greatest risk of bacterial co-infection using clinical criteria alone or in combination with rapid diagnostic biomarker tests. Methods: A Phase I/II open-label trial comparing three doses of azithromycin: 10, 15 and 20 mg/kg spanning the lowest to highest mg/kg doses previously demonstrated to be equally effective as parenteral treatment for other salmonellae infection. Children with the highest risk of bacterial infection will receive five days of azithromycin and followed for 90 days. We will generate relevant pharmacokinetic data by sparse sampling during dosing intervals. We will use population pharmacokinetic modelling to determine the optimal azithromycin dose in severe malaria and investigate azithromycin exposure to change in C-reactive protein, a putative marker of sepsis at 72 hours, and microbiological cure (seven-day), alone and as a composite with seven-day survival. We will also evaluate whether a combination of clinical, point-of-care diagnostic tests, and/or biomarkers can accurately identify the sub-group of severe malaria with culture-proven bacteraemia by comparison with a control cohort of children hospitalized with severe malaria at low risk of bacterial co-infection. Discussion : We plan to study azithromycin because of its favourable microbiological spectrum, its inherent antimalarial and immunomodulatory properties and dosing and safety profile. This study will generate new data to inform the design and sample size for definitive Phase III trial evaluation. Registration: ISRCTN49726849 (27 th October 2017).

Published
2021

31. No need for secondary Pneumocystis jirovecii pneumonia prophylaxis in adult people living with HIV from Europe on ART with suppressed viraemia and a CD4 cell count greater than 100 cells/µL

Author

Atkinson, A. Miro, J.M. Mocroft, A. Reiss, P. Kirk, O. Morlat, P. Ghosn, J. Stephan, C. Mussini, C. Antoniadou, A. Doerholt, K. Girardi, E. De Wit, S. Kraus, D. Zwahlen, M. Furrer, H. De Wit, S. Antoniadou, A. Castagna, A. Doerholt, K. Fätkenheuer, G. Raben, D. Teira, R. Zangerle, R. Judd, A. Zangerle, R. Touloumi, G. Warszawski, J. Meyer, L. Dabis, F. Krause, M.M. Leport, C. Wittkop, L. Wit, F. Prins, M. Bucher, H. Gibb, D. Fätkenheuer, G. Del Amo, J. Obel, N. Thorne, C. Pérez-Hoyos, S. Hamouda, O. Bartmeyer, B. Chkhartishvili, N. Noguera-Julian, A. Antinori, A. d’Arminio Monforte, A. Brockmeyer, N. Prieto, L. Conejo, P.R. Soriano-Arandes, A. Battegay, M. Kouyos, R. Casabona, J. Goetghebuer, T. Sönnerborg, A. Torti, C. Sabin, C. Teira, R. Garrido, M. Haerry, D. Costagliola, D. d’Arminio-Monforte, A. del Amo, J. Raben, D. Chêne, G. Judd, A. Conejo, P.R. Barger, D. Schwimmer, C. Termote, M. Wittkop, L. Frederiksen, C.M. Raben, D. Brandt, R.S. Berenguer, J. Bohlius, J. Bouteloup, V. Bucher, H. Cozzi-Lepri, A. Dabis, F. d’Arminio Monforte, A. Davies, M.-A. del Amo, J. Dorrucci, M. Dunn, D. Egger, M. Guiguet, M. Grabar, S. Judd, A. Lambotte, O. Leroy, V. Lodi, S. Matheron, S. Meyer, L. Monge, S. Nakagawa, F. Paredes, R. Phillips, A. Puoti, M. Rohner, E. Schomaker, M. Smit, C. Sterne, J. Thiebaut, R. Thorne, C. Wqetu, C. van der Valk, M. Wittkop, L. the Opportunistic Infections Working Group of the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) study in EuroCOORD

Abstract

Introduction: Since the beginning of the HIV epidemic in resource-rich countries, Pneumocystis jirovecii pneumonia (PjP) is one of the most frequent opportunistic AIDS-defining infections. The Collaboration of Observational HIV Epidemiological Research Europe (COHERE) has shown that primary Pneumocystis jirovecii Pneumonia (PjP) prophylaxis can be safely withdrawn in patients with CD4 counts of 100 to 200 cells/µL if plasma HIV-RNA is suppressed on combination antiretroviral therapy. Whether this holds true for secondary prophylaxis is not known, and this has proved difficult to determine due to the much lower population at risk. Methods: We estimated the incidence of secondary PjP by including patient data collected from 1998 to 2015 from the COHERE cohort collaboration according to time-updated CD4 counts, HIV-RNA and use of PjP prophylaxis in persons >16 years of age. We fitted a Poisson generalized additive model in which the smoothed effect of CD4 was modelled by a restricted cubic spline, and HIV-RNA was stratified as low (10,000copies/mL). Results: There were 373 recurrences of PjP during 74,295 person-years (py) in 10,476 patients. The PjP incidence in the different plasma HIV-RNA strata differed significantly and was lowest in the low stratum. For patients off prophylaxis with CD4 counts between 100 and 200 cells/µL and HIV-RNA below 400 copies/mL, the incidence of recurrent PjP was 3.9 (95% CI: 2.0 to 5.8) per 1000 py, not significantly different from patients on prophylaxis in the same stratum (1.9, 95% CI: 0.1 to 3.7). Conclusions: HIV viraemia importantly affects the risk of recurrent PjP. In virologically suppressed patients on ART with CD4 counts of 100 to 200/µL, the incidence of PjP off prophylaxis is below 10/1000 py. Secondary PjP prophylaxis may be safely withheld in such patients. While European guidelines recommend discontinuing secondary PjP prophylaxis only if CD4 counts rise above 200 cells/mL, the latest US Guidelines consider secondary prophylaxis discontinuation even in patients with a CD4 count above 100 cells/µL and suppressed viral load. Our results strengthen and support this US recommendation. © 2021 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.

Published
2021

32. Predictors of faster virological suppression in early treated infants with perinatal HIV from Europe and Thailand

Author

Chan, M. K., Goodall, R., Judd, A., Klein, N., Chiappini, E., Klimkait, T., Ngo-Giang-Huong, Nicole, Palma, P., Rossi, P., Thorne, C., Turkova, A., Zangari, P., Rojo, P., Babiker, A. G. A., Fraaij, P. L., Pajkrt, D., Marques, L., Collins, I. J., Gibb, D. M., Gonzalez-Tome, M. I., Ramos, J. T., Navarro, M. L., Noguera-Julian, A., Warszawski, J., Konigs, C., Spoulou, V., Prata, F., Goetghebuer, T., Galli, L., Naver, L., Giaquinto, C., Marczynska, M., Okhonskaia, L., Malyuta, R., Volokha, A., Ene, L., Gibb, D., Watters, S., Chan, M., McCoy, L., Babiker, A., Marcelin, A. G., Calvez, V., Munoz, M. A., Wahren, B., Foster, C., Cotton, M., Robb, M., Ananworanich, J., Claiden, P., Pillay, D., Persaud, D., De Boer, R. J., Schroter, J., Anelone, A. J. N., Puthanakit, T., Ceci, A., Giannuzzi, V., Luzuriaga, K., Chomont, N., Cameron, M., Cancrini, C., Yates, A., Kuhn, L., Violari, A., Otwombe, K., Pepponi, I., Rocchi, F., Rinaldi, S., Tagarro, A., Lain, M. G., Vaz, P., Lopez, E., Nhampossa, T., EPPICC study group, and EPIICAL study groups

Subjects
early combination antiretroviral therapy, predictors, infants, perinatal HIV, virological suppression
Abstract

Objective: To identify predictors of faster time to virological suppression among infants starting combination antiretroviral therapy (cART) early in infancy. Design: Cohort study of infants from Europe and Thailand included in studies participating in the European Pregnancy and Paediatric HIV Cohort Collaboration. Methods: Infants with perinatal HIV starting cART aged less than 6 months with at least 1 viral load measurement within 15 months of cART initiation were included. Multi-variable interval-censored flexible parametric proportional hazards models were used to assess predictors of faster virological suppression, with timing of suppression assumed to lie in the interval between last viral load at least 400 and first viral load less than 400 copies/ml. Results: Of 420 infants, 59% were female and 56% from Central/Western Europe, 26% United Kingdom/Ireland, 15% Eastern Europe and 3% Thailand; 46 and 54% started a boosted protease inhibitor-based or nonnucleoside reverse transcriptase inhibitor-based regimen, respectively. At cART initiation, the median age, CD4(+) % and viral load were 2.9 [interquartile range (IQR): 1.4-4.1] months, 34 (IQR: 24-45)% and 5.5 (IQR: 4.5-6.0) log(10) copies/ml, respectively. Overall, an estimated 89% (95% confidence interval: 86-92%) achieved virological suppression within 12 months of cART start. In multivariable analysis, younger age [adjusted hazard ratio (aHR): 0.84 per month older; P < 0.001], higher CD4(+) % (aHR: 1.11 per 10% higher; P=0.010) and lower log(10) viral load (aHR: 0.85 per log(10) higher; P < 0.001) at cART initiation independently predicted faster virological suppression. Conclusion: We observed a significant independent effect of age at cART initiation, even within a narrow 6 months window from birth. These findings support the earliest feasible cART initiation in infants and suggest that early therapy influences key virological and immunological parameters that could have important consequences for long-term health.

Published
2019

33. Global temporal changes in the proportion of children with advanced disease at the start of combination antiretroviral therapy in an era of changing criteria for treatment initiation

Author

Panayidou, K, Davies, M, Anderegg, N, Egger, M, Fatti, G, Vinikoor, M, Sawry, S, Ehmer, J, Eley, B, Phiri, S, Technau, K, Chimbetete, C, Rabie, H, Boulle, A, Tanser, F, Wood, R, Wools-Kaloustian, K, Vreeman, R, Oyaro, P, Ayaya, S, Nakigozi, G, Musick, B, Yiannoutsos, C, Amorissani-Folquet, M, Takassi, E, Sylla, M, Renner, L, Malateste, K, Desmonde, S, Leroy, V, Kurniati, N, Hansudewechakul, R, Nguyen, L, Ly, P, Truong, K, Kariminia, A, Sohn, A, Edmonds, A, Yumo, H, Dusingize, J, Yotebieng, M, Judd, A, Rojo, P, Smit, C, Grabar, S, Warszwarski, J, Chene, G, Raban, D, Patel, K, Seage, G, Van Dyke, R, Oleske, J, Williams, P, Abzug, M, Succi, R, Machado, D, Pinto, J, Rouzier, V, Luque, M, Mejia, F, Khol, V, Tucker, J, Kumarasamy, N, Saghayam, S, Chandrasekaran, E, Wati, D, Vedaswari, D, Malino, I, Muktiarti, D, Fong, S, Lim, M, Daut, F, Nik Yusoff, N, Mohamad, P, Mohamed, T, Drawis, M, Nallusamy, R, Chan, K, Sudjaritruk, T, Sirisanthana, V, Aurpibul, L, Oberdorfer, P, Denjanta, S, Watanaporn, S, Kongphonoi, A, Lumbiganon, P, Kosalaraksa, P, Tharnprisan, P, Udomphanit, T, Jourdain, G, Puthanakit, T, Anugulruengkitt, S, Phadungphon, C, Chokephaibulkit, K, Lapphra, K, Phongsamart, W, Sricharoenchai, S, Du, Q, Nguyen, C, Do, V, Ha, T, An, V, Khu, D, Pham, A, Le, O, Ross, J, Sethaputra, C, Law, M, Cahn, P, Cesar, C, Fink, V, Sued, O, Dell'Isola, E, Perez, H, Valiente, J, Yamamoto, C, Grinsztejn, B, Veloso, V, Luz, P, de Boni, R, Wagner, S, Friedman, R, Moreira, R, Ferreira, F, Maia, M, de Menezes Succi, R, Barbosa Gouv E A, A, Wolff, M, Cortes, C, Rodriguez, M, Allendes, G, Pape, J, Marcelin, A, Perodin, C, Padgett, D, Madero, J, Ramirez, B, Belaunzaran, P, Vega, Y, Gotuzzo, E, Carriquiry, G, Mcgowan, C, Shepherd, B, Sterling, T, Jayathilake, K, Person, A, Rebeiro, P, Giganti, M, Castilho, J, Duda, S, Maruri, F, Vansell, H, P E Lagie, N, Gateretse, P, Munezero, J, Nitereka, V, Niyongabo, T, Twizere, C, Bukuru, H, Nahimana, T, Biziragusenyuka, J, Manyundo, R, Atsu, K, Mbuh, T, Ajeh, R, Benwi, M, Dzudie, A, Mbuh, A, Ngamani, M, Nkome, V, Amadou, D, Ngassam, E, Pefura Yone, E, Ewanoge, A, Fuhngwa, N, Moki, C, Akele, C, Kitetele, F, Lelo, P, Tabala, M, Okitolonda, E, Wenzi, L, Diafouka, M, Ekat, M, Nsonde, D, Mafou, A, Ntarambirwa, F, Tuyishimire, Y, Hakizimana, T, Ayinkamiye, J, Mukantwali, S, Kayitesi, H, Uwamahoro, O, Habumuremyi, V, Mukamana, J, Kubwimana, G, Mugenzi, P, Muhoza, B, Munyaneza, A, Ndahiro, E, Nyiransabimana, D, D'Amour Sinayobye, J, Sugira, V, Benekigeri, C, Mbaraga, G, Adedimeji, A, Anastos, K, Dilorenzo, M, Murchison, L, Addison, D, Baker, M, Brazier, E, Jones, H, Kelvin, E, Kulkarni, S, Nash, D, Tymejczyk, O, Elul, B, Cai, X, Hoover, D, Kim, H, Li, C, Shi, Q, Lancaster, K, Kuniholm, M, Parcesepe, A, Kimmel, A, Mcnairy, M, Diero, L, Plus, A, Bukusi, E, Ssali, J, Nalugoda, F, Somi, G, Lyamuya, R, Ngonyani, K, Lugina, E, Urassa, M, Michael, D, Zannou, M, Poda, A, Sarfo, F, Messou, E, Chenal, H, Minga, K, Bissagnene, E, Tanon, A, Seydi, M, Patassi, A, Koumakpai-Adeothy, S, N'Gbeche, S, Bosse, C, Kouakou, K, Folquet, M, Eboua, F, Traore, F, Dabis, F, Arrive, E, Balestre, E, Becquet, R, Bernard, C, Arikawa, S, Doring, A, Jaquet, A, Rabourdin, E, Tiendrebeogo, T, Jesson, J, Ekouevi, D, Azani, J, Coffi E, P, Gnepa, G, Kouadio, C, Tchounga, B, Maartens, G, Lettow, M, Muhairwe, J, Jores, A, Kamenova, K, Fox, M, Prozesky, H, Zangerle, R, Touloumi, G, Warszawski, J, Meyer, L, Krause, M, Ghosn, J, Leport, C, Wittkop, L, Reiss, P, Wit, F, Prins, M, Bucher, H, Gibb, D, Fatkenheuer, G, Del Amo, J, Obel, N, Thorne, C, Mocroft, A, Kirk, O, Stephan, C, Perez-Hoyos, S, Hamouda, O, Bartmeyer, B, Chkhartishvili, N, Noguera-Julian, A, Antinori, A, D'Arminio Monforte, A, Brockmeyer, N, Prieto, L, Conejo, P, Soriano-Arandes, A, Battegay, M, Kouyos, R, Mussini, C, Tookey, P, Casabona, J, Miro, J, Castagna, A, Konopnick, D, Goetghebuer, T, Sonnerborg, A, Torti, C, Sabin, C, Teira, R, Garrido, M, Haerry, D, de Wit, S, Costagliola, D, Raben, D, Barger, D, Schwimmer, C, Termote, M, Campbell, M, Frederiksen, C, Friis-Moller, N, Kjaer, J, Brandt, R, Berenguer, J, Bohlius, J, Bouteloup, V, Cozzi-Lepri, A, Dorrucci, M, Dunn, D, Furrer, H, Guiguet, M, Lambotte, O, Lodi, S, Matheron, S, Monge, S, Nakagawa, F, Paredes, R, Phillips, A, Puoti, M, Rohner, E, Schomaker, M, Sterne, J, Thiebaut, R, van der Valk, M, Hazra, R, Heckman, B, O'Gara, E, Siminski, S, Panayidou K., Davies M. -A., Anderegg N., Egger M., Fatti G., Vinikoor M., Sawry S., Ehmer J., Eley B., Phiri S., Technau K. -G. u. N., Chimbetete C., Rabie H., Boulle A., Tanser F., Wood R., Wools-Kaloustian K., Vreeman R., Oyaro P., Ayaya S., Nakigozi G., Musick B., Yiannoutsos C., Amorissani-Folquet M., Takassi E., Sylla M., Renner L., Malateste K., Desmonde S., Leroy V., Kurniati N., Hansudewechakul R., Nguyen L. V., Ly P. S., Truong K. H., Kariminia A., Sohn A. H., Edmonds A., Yumo H. A., Dusingize J. C., Yotebieng M., Judd A., Rojo P., Smit C., Grabar S., Warszwarski J., Chene G., Raban D., Patel K., Seage G. R., Van Dyke R. B., Oleske J., Williams P. L., Abzug M. J., Succi R., Machado D. M., Pinto J., Rouzier V., Luque M., Mejia F., Khol V., Tucker J., Kumarasamy N., Saghayam S., Chandrasekaran E., Wati D. K., Vedaswari D., Malino I. Y., Muktiarti D., Fong S. M., Lim M., Daut F., Nik Yusoff N. K., Mohamad P., Mohamed T. J., Drawis M. R., Nallusamy R., Chan K. C., Sudjaritruk T., Sirisanthana V., Aurpibul L., Oberdorfer P., Denjanta S., Watanaporn S., Kongphonoi A., Lumbiganon P., Kosalaraksa P., Tharnprisan P., Udomphanit T., Jourdain G., Puthanakit T., Anugulruengkitt S., Phadungphon C., Chokephaibulkit K., Lapphra K., Phongsamart W., Sricharoenchai S., Du Q. T., Nguyen C. H., Do V. C., Ha T. M., An V. T., Khu D. T. K., Pham A. N., Nguyen L. T., Le O. N., Ross J. L., Sethaputra C., Law M. G., Cahn P., Cesar C., Fink V., Sued O., Dell'isola E., Perez H., Valiente J., Yamamoto C., Grinsztejn B., Veloso V., Luz P., de Boni R., Wagner S. C., Friedman R., Moreira R., Ferreira F., Maia M., de Menezes Succi R. C., Barbosa Gouv E A A. F. a. T., Wolff M., Cortes C., Rodriguez M. F., Allendes G., Pape J. W., Marcelin A., Perodin C., Luque M. T., Padgett D., Madero J. S., Ramirez B. C., Belaunzaran P., Vega Y. C., Gotuzzo E., Carriquiry G., McGowan C. C., Shepherd B. E., Sterling T., Jayathilake K., Person A. K., Rebeiro P. F., Giganti M., Castilho J., Duda S. N., Maruri F., Vansell H., P E Lagie N., Gateretse P., Munezero J., Nitereka V., Niyongabo T., Twizere C., Bukuru H., Nahimana T., Biziragusenyuka J., Manyundo R. S., Atsu K., Mbuh T., Ajeh R., Benwi M., Dzudie A., Mbuh A., Ngamani M. L., Nkome V., Amadou D., Ngassam E., Pefura Yone E. W., Ewanoge A. N., Fuhngwa N., Moki C., Akele C., Kitetele F., Lelo P., Tabala M., Okitolonda E. W., Wenzi L., Diafouka M., Ekat M. H., Nsonde D. M., Mafou A., Ntarambirwa F., Tuyishimire Y., Hakizimana T., Ayinkamiye J., Mukantwali S., Kayitesi H., Uwamahoro O., Habumuremyi V., Mukamana J., Kubwimana G., Mugenzi P., Muhoza B., Munyaneza A., Ndahiro E., Nyiransabimana D., D'Amour Sinayobye J., Sugira V., Benekigeri C., Mbaraga G., Adedimeji A., Anastos K., Dilorenzo M., Murchison L., Ross J., Addison D., Baker M., Brazier E., Jones H., Kelvin E., Kulkarni S., Nash D., Tymejczyk O., Elul B., Cai X., Hoover D., Kim H. -Y., Li C., Shi Q., Lancaster K., Kuniholm M., Parcesepe A., Duda S., Kimmel A., McNairy M., Diero L., Plus A. M. P. A. T. H., Bukusi E., Ssali J., Nalugoda F., Somi G. R., Lyamuya R. E., Ngonyani K., Lugina E., Urassa M., Michael D., Zannou M. D., Poda A., Sarfo F. S., Messou E., Chenal H., Minga K. A., Bissagnene E., Tanon A., Seydi M., Patassi A. A., Koumakpai-Adeothy S. A., Renner L. A., N'gbeche S. M., Bosse C. A., Kouakou K., Folquet M. A., Eboua F. c. O. T., Traore F. D., Dabis F. c. O., Arrive E., Balestre E., Becquet R., Bernard C., Arikawa S. C., Doring A., Jaquet A., Rabourdin E., Tiendrebeogo T., Jesson J., Ekouevi D. K., Azani J. -C., Coffi E P., Gnepa G., Kouadio C. G. K., Tchounga B., Maartens G., Lettow M. V., Muhairwe J., Jores A., Kamenova K., Fox M. P., Prozesky H., Zangerle R., Touloumi G., Warszawski J., Meyer L., Krause M. M., Ghosn J., Leport C., Wittkop L., Reiss P., Wit F., Prins M., Bucher H., Gibb D., Fatkenheuer G., Del Amo J., Obel N., Thorne C., Mocroft A., Kirk O., Stephan C., Perez-Hoyos S., Hamouda O., Bartmeyer B., Chkhartishvili N., Noguera-Julian A., Antinori A., D'Arminio Monforte A., Brockmeyer N., Prieto L., Conejo P. R., Soriano-Arandes A., Battegay M., Kouyos R., Mussini C., Tookey P., Casabona J., Miro J. M., Castagna A., Konopnick D., Goetghebuer T., Sonnerborg A., Torti C., Sabin C., Teira R., Garrido M., Haerry D., de Wit S., Costagliola D., Raben D., Barger D., Schwimmer C., Termote M., Campbell M., Frederiksen C. M., Friis-Moller N., Kjaer J., Brandt R. S., Berenguer J., Bohlius J., Bouteloup V., Cozzi-Lepri A., Dorrucci M., Dunn D., Furrer H., Guiguet M., Lambotte O., Lodi S., Matheron S., Miro J. M. a., Monge S., Nakagawa F., Paredes R., Phillips A., Puoti M., Rohner E., Schomaker M., Sterne J., Thiebaut R., van der Valk M., Hazra R., Heckman B., O'gara E., Siminski S., Panayidou, K, Davies, M, Anderegg, N, Egger, M, Fatti, G, Vinikoor, M, Sawry, S, Ehmer, J, Eley, B, Phiri, S, Technau, K, Chimbetete, C, Rabie, H, Boulle, A, Tanser, F, Wood, R, Wools-Kaloustian, K, Vreeman, R, Oyaro, P, Ayaya, S, Nakigozi, G, Musick, B, Yiannoutsos, C, Amorissani-Folquet, M, Takassi, E, Sylla, M, Renner, L, Malateste, K, Desmonde, S, Leroy, V, Kurniati, N, Hansudewechakul, R, Nguyen, L, Ly, P, Truong, K, Kariminia, A, Sohn, A, Edmonds, A, Yumo, H, Dusingize, J, Yotebieng, M, Judd, A, Rojo, P, Smit, C, Grabar, S, Warszwarski, J, Chene, G, Raban, D, Patel, K, Seage, G, Van Dyke, R, Oleske, J, Williams, P, Abzug, M, Succi, R, Machado, D, Pinto, J, Rouzier, V, Luque, M, Mejia, F, Khol, V, Tucker, J, Kumarasamy, N, Saghayam, S, Chandrasekaran, E, Wati, D, Vedaswari, D, Malino, I, Muktiarti, D, Fong, S, Lim, M, Daut, F, Nik Yusoff, N, Mohamad, P, Mohamed, T, Drawis, M, Nallusamy, R, Chan, K, Sudjaritruk, T, Sirisanthana, V, Aurpibul, L, Oberdorfer, P, Denjanta, S, Watanaporn, S, Kongphonoi, A, Lumbiganon, P, Kosalaraksa, P, Tharnprisan, P, Udomphanit, T, Jourdain, G, Puthanakit, T, Anugulruengkitt, S, Phadungphon, C, Chokephaibulkit, K, Lapphra, K, Phongsamart, W, Sricharoenchai, S, Du, Q, Nguyen, C, Do, V, Ha, T, An, V, Khu, D, Pham, A, Le, O, Ross, J, Sethaputra, C, Law, M, Cahn, P, Cesar, C, Fink, V, Sued, O, Dell'Isola, E, Perez, H, Valiente, J, Yamamoto, C, Grinsztejn, B, Veloso, V, Luz, P, de Boni, R, Wagner, S, Friedman, R, Moreira, R, Ferreira, F, Maia, M, de Menezes Succi, R, Barbosa Gouv E A, A, Wolff, M, Cortes, C, Rodriguez, M, Allendes, G, Pape, J, Marcelin, A, Perodin, C, Padgett, D, Madero, J, Ramirez, B, Belaunzaran, P, Vega, Y, Gotuzzo, E, Carriquiry, G, Mcgowan, C, Shepherd, B, Sterling, T, Jayathilake, K, Person, A, Rebeiro, P, Giganti, M, Castilho, J, Duda, S, Maruri, F, Vansell, H, P E Lagie, N, Gateretse, P, Munezero, J, Nitereka, V, Niyongabo, T, Twizere, C, Bukuru, H, Nahimana, T, Biziragusenyuka, J, Manyundo, R, Atsu, K, Mbuh, T, Ajeh, R, Benwi, M, Dzudie, A, Mbuh, A, Ngamani, M, Nkome, V, Amadou, D, Ngassam, E, Pefura Yone, E, Ewanoge, A, Fuhngwa, N, Moki, C, Akele, C, Kitetele, F, Lelo, P, Tabala, M, Okitolonda, E, Wenzi, L, Diafouka, M, Ekat, M, Nsonde, D, Mafou, A, Ntarambirwa, F, Tuyishimire, Y, Hakizimana, T, Ayinkamiye, J, Mukantwali, S, Kayitesi, H, Uwamahoro, O, Habumuremyi, V, Mukamana, J, Kubwimana, G, Mugenzi, P, Muhoza, B, Munyaneza, A, Ndahiro, E, Nyiransabimana, D, D'Amour Sinayobye, J, Sugira, V, Benekigeri, C, Mbaraga, G, Adedimeji, A, Anastos, K, Dilorenzo, M, Murchison, L, Addison, D, Baker, M, Brazier, E, Jones, H, Kelvin, E, Kulkarni, S, Nash, D, Tymejczyk, O, Elul, B, Cai, X, Hoover, D, Kim, H, Li, C, Shi, Q, Lancaster, K, Kuniholm, M, Parcesepe, A, Kimmel, A, Mcnairy, M, Diero, L, Plus, A, Bukusi, E, Ssali, J, Nalugoda, F, Somi, G, Lyamuya, R, Ngonyani, K, Lugina, E, Urassa, M, Michael, D, Zannou, M, Poda, A, Sarfo, F, Messou, E, Chenal, H, Minga, K, Bissagnene, E, Tanon, A, Seydi, M, Patassi, A, Koumakpai-Adeothy, S, N'Gbeche, S, Bosse, C, Kouakou, K, Folquet, M, Eboua, F, Traore, F, Dabis, F, Arrive, E, Balestre, E, Becquet, R, Bernard, C, Arikawa, S, Doring, A, Jaquet, A, Rabourdin, E, Tiendrebeogo, T, Jesson, J, Ekouevi, D, Azani, J, Coffi E, P, Gnepa, G, Kouadio, C, Tchounga, B, Maartens, G, Lettow, M, Muhairwe, J, Jores, A, Kamenova, K, Fox, M, Prozesky, H, Zangerle, R, Touloumi, G, Warszawski, J, Meyer, L, Krause, M, Ghosn, J, Leport, C, Wittkop, L, Reiss, P, Wit, F, Prins, M, Bucher, H, Gibb, D, Fatkenheuer, G, Del Amo, J, Obel, N, Thorne, C, Mocroft, A, Kirk, O, Stephan, C, Perez-Hoyos, S, Hamouda, O, Bartmeyer, B, Chkhartishvili, N, Noguera-Julian, A, Antinori, A, D'Arminio Monforte, A, Brockmeyer, N, Prieto, L, Conejo, P, Soriano-Arandes, A, Battegay, M, Kouyos, R, Mussini, C, Tookey, P, Casabona, J, Miro, J, Castagna, A, Konopnick, D, Goetghebuer, T, Sonnerborg, A, Torti, C, Sabin, C, Teira, R, Garrido, M, Haerry, D, de Wit, S, Costagliola, D, Raben, D, Barger, D, Schwimmer, C, Termote, M, Campbell, M, Frederiksen, C, Friis-Moller, N, Kjaer, J, Brandt, R, Berenguer, J, Bohlius, J, Bouteloup, V, Cozzi-Lepri, A, Dorrucci, M, Dunn, D, Furrer, H, Guiguet, M, Lambotte, O, Lodi, S, Matheron, S, Monge, S, Nakagawa, F, Paredes, R, Phillips, A, Puoti, M, Rohner, E, Schomaker, M, Sterne, J, Thiebaut, R, van der Valk, M, Hazra, R, Heckman, B, O'Gara, E, Siminski, S, Panayidou K., Davies M. -A., Anderegg N., Egger M., Fatti G., Vinikoor M., Sawry S., Ehmer J., Eley B., Phiri S., Technau K. -G. u. N., Chimbetete C., Rabie H., Boulle A., Tanser F., Wood R., Wools-Kaloustian K., Vreeman R., Oyaro P., Ayaya S., Nakigozi G., Musick B., Yiannoutsos C., Amorissani-Folquet M., Takassi E., Sylla M., Renner L., Malateste K., Desmonde S., Leroy V., Kurniati N., Hansudewechakul R., Nguyen L. V., Ly P. S., Truong K. H., Kariminia A., Sohn A. H., Edmonds A., Yumo H. A., Dusingize J. C., Yotebieng M., Judd A., Rojo P., Smit C., Grabar S., Warszwarski J., Chene G., Raban D., Patel K., Seage G. R., Van Dyke R. B., Oleske J., Williams P. L., Abzug M. J., Succi R., Machado D. M., Pinto J., Rouzier V., Luque M., Mejia F., Khol V., Tucker J., Kumarasamy N., Saghayam S., Chandrasekaran E., Wati D. K., Vedaswari D., Malino I. Y., Muktiarti D., Fong S. M., Lim M., Daut F., Nik Yusoff N. K., Mohamad P., Mohamed T. J., Drawis M. R., Nallusamy R., Chan K. C., Sudjaritruk T., Sirisanthana V., Aurpibul L., Oberdorfer P., Denjanta S., Watanaporn S., Kongphonoi A., Lumbiganon P., Kosalaraksa P., Tharnprisan P., Udomphanit T., Jourdain G., Puthanakit T., Anugulruengkitt S., Phadungphon C., Chokephaibulkit K., Lapphra K., Phongsamart W., Sricharoenchai S., Du Q. T., Nguyen C. H., Do V. C., Ha T. M., An V. T., Khu D. T. K., Pham A. N., Nguyen L. T., Le O. N., Ross J. L., Sethaputra C., Law M. G., Cahn P., Cesar C., Fink V., Sued O., Dell'isola E., Perez H., Valiente J., Yamamoto C., Grinsztejn B., Veloso V., Luz P., de Boni R., Wagner S. C., Friedman R., Moreira R., Ferreira F., Maia M., de Menezes Succi R. C., Barbosa Gouv E A A. F. a. T., Wolff M., Cortes C., Rodriguez M. F., Allendes G., Pape J. W., Marcelin A., Perodin C., Luque M. T., Padgett D., Madero J. S., Ramirez B. C., Belaunzaran P., Vega Y. C., Gotuzzo E., Carriquiry G., McGowan C. C., Shepherd B. E., Sterling T., Jayathilake K., Person A. K., Rebeiro P. F., Giganti M., Castilho J., Duda S. N., Maruri F., Vansell H., P E Lagie N., Gateretse P., Munezero J., Nitereka V., Niyongabo T., Twizere C., Bukuru H., Nahimana T., Biziragusenyuka J., Manyundo R. S., Atsu K., Mbuh T., Ajeh R., Benwi M., Dzudie A., Mbuh A., Ngamani M. L., Nkome V., Amadou D., Ngassam E., Pefura Yone E. W., Ewanoge A. N., Fuhngwa N., Moki C., Akele C., Kitetele F., Lelo P., Tabala M., Okitolonda E. W., Wenzi L., Diafouka M., Ekat M. H., Nsonde D. M., Mafou A., Ntarambirwa F., Tuyishimire Y., Hakizimana T., Ayinkamiye J., Mukantwali S., Kayitesi H., Uwamahoro O., Habumuremyi V., Mukamana J., Kubwimana G., Mugenzi P., Muhoza B., Munyaneza A., Ndahiro E., Nyiransabimana D., D'Amour Sinayobye J., Sugira V., Benekigeri C., Mbaraga G., Adedimeji A., Anastos K., Dilorenzo M., Murchison L., Ross J., Addison D., Baker M., Brazier E., Jones H., Kelvin E., Kulkarni S., Nash D., Tymejczyk O., Elul B., Cai X., Hoover D., Kim H. -Y., Li C., Shi Q., Lancaster K., Kuniholm M., Parcesepe A., Duda S., Kimmel A., McNairy M., Diero L., Plus A. M. P. A. T. H., Bukusi E., Ssali J., Nalugoda F., Somi G. R., Lyamuya R. E., Ngonyani K., Lugina E., Urassa M., Michael D., Zannou M. D., Poda A., Sarfo F. S., Messou E., Chenal H., Minga K. A., Bissagnene E., Tanon A., Seydi M., Patassi A. A., Koumakpai-Adeothy S. A., Renner L. A., N'gbeche S. M., Bosse C. A., Kouakou K., Folquet M. A., Eboua F. c. O. T., Traore F. D., Dabis F. c. O., Arrive E., Balestre E., Becquet R., Bernard C., Arikawa S. C., Doring A., Jaquet A., Rabourdin E., Tiendrebeogo T., Jesson J., Ekouevi D. K., Azani J. -C., Coffi E P., Gnepa G., Kouadio C. G. K., Tchounga B., Maartens G., Lettow M. V., Muhairwe J., Jores A., Kamenova K., Fox M. P., Prozesky H., Zangerle R., Touloumi G., Warszawski J., Meyer L., Krause M. M., Ghosn J., Leport C., Wittkop L., Reiss P., Wit F., Prins M., Bucher H., Gibb D., Fatkenheuer G., Del Amo J., Obel N., Thorne C., Mocroft A., Kirk O., Stephan C., Perez-Hoyos S., Hamouda O., Bartmeyer B., Chkhartishvili N., Noguera-Julian A., Antinori A., D'Arminio Monforte A., Brockmeyer N., Prieto L., Conejo P. R., Soriano-Arandes A., Battegay M., Kouyos R., Mussini C., Tookey P., Casabona J., Miro J. M., Castagna A., Konopnick D., Goetghebuer T., Sonnerborg A., Torti C., Sabin C., Teira R., Garrido M., Haerry D., de Wit S., Costagliola D., Raben D., Barger D., Schwimmer C., Termote M., Campbell M., Frederiksen C. M., Friis-Moller N., Kjaer J., Brandt R. S., Berenguer J., Bohlius J., Bouteloup V., Cozzi-Lepri A., Dorrucci M., Dunn D., Furrer H., Guiguet M., Lambotte O., Lodi S., Matheron S., Miro J. M. a., Monge S., Nakagawa F., Paredes R., Phillips A., Puoti M., Rohner E., Schomaker M., Sterne J., Thiebaut R., van der Valk M., Hazra R., Heckman B., O'gara E., and Siminski S.

Abstract

Introduction: The CD4 cell count and percent at initiation of combination antiretroviral therapy (cART) are measures of advanced HIV disease and thus are important indicators of programme performance for children living with HIV. In particular, World Health Organization (WHO) 2017 guidelines on advanced HIV disease noted that >80% of children aged <5 years started cART with WHO Stage 3 or 4 disease or severe immune suppression. We compared temporal trends in CD4 measures at cART start in children from low-, middle- and high-income countries, and examined the effect of WHO treatment initiation guidelines on reducing the proportion of children initiating cART with advanced disease. Methods: We included children aged <16 years from the International Epidemiology Databases to Evaluate acquired immunodeficiency syndrome (AIDS) (IeDEA) Collaboration (Caribbean, Central and South America, Asia-Pacific, and West, Central, East and Southern Africa), the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE), the North American Pediatric HIV/AIDS Cohort Study (PHACS) and International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) 219C study. Severe immunodeficiency was defined using WHO guidelines. We used generalized weighted additive mixed effect models to analyse temporal trends in CD4 measurements and piecewise regression to examine the impact of 2006 and 2010 WHO cART initiation guidelines. Results: We included 52,153 children from fourteen low-, eight lower middle-, five upper middle- and five high-income countries. From 2004 to 2013, the estimated percentage of children starting cART with severe immunodeficiency declined from 70% to 42% (low-income), 67% to 64% (lower middle-income) and 61% to 43% (upper middle-income countries). In high-income countries, severe immunodeficiency at cART initiation declined from 45% (1996) to 14% (2012). There were annual decreases in the percentage of children with severe immuno

Published
2018

34. Immunological and virological response to antiretroviral treatment in migrant and native men and women in Western Europe; is benefit equal for all?

Author

Monge, S, Mocroft, A, Sabin, A, Touloumi, G, Sighem, A, Abgrall, S, Dray-Spira, R, Spire, B, Castagna, A, Mussini, C, Zangerle, R, Hessamfar, M, Anderson, J, Hamouda, O, Ehren, K, Obel, N, Kirk, O, Antinori, A, Girardi, E, Saracino, A, Calmy, A, Wit, S, Wittkop, L, Bucher, C, Montoliu, A, Raben, D, Prins, M, Meyer, L, Chene, G, Burns, F, Amo, J, Judd, A, Warszawski, J, Dabis, F, Krause, M, Ghosn, J, Leport, C, Reiss, P, Wit, F, Bucher, H, Gibb, D, Fatkenheuer, G, Thorne, C, Stephan, C, Perez-Hoyos, S, Bartmeyer, B, Chkhartishvili, N, Noguera-Julian, A, Monforte, A, Brockmeyer, N, Prieto, L, Conejo, P, Soriano-Arandes, A, Battegay, M, Kouyos, R, Tookey, P, Casabona, J, Miro, J, Konopnick, D, Goetghebuer, T, Sonnerborg, A, Torti, C, Sabin, C, Teira, R, Garrido, M, Haerry, D, Miro, M, Costagliola, D, d'Arminio-Monforte, A, Barger, D, Schwimmer, C, Termote, M, Campbell, M, Frederiksen, C, Friis-Moller, N, Kjaer, J, Brandt, R, Berenguer, J, Bohlius, J, Bouteloup, V, Cozzi-Lepri, A, Davies, M, Dorrucci, M, Dunn, D, Egger, M, Furrer, H, Guiguet, M, Grabar, S, Lambotte, O, Leroy, V, Lodi, S, Matheron, S, Nakagawa, F, Paredes, R, Phillips, A, Puoti, M, Rohner, E, Schomaker, M, Smit, C, Sterne, J, Thiebaut, R, Valk, M, Monge S., Mocroft A., Sabin A., Touloumi G., Sighem A., Abgrall S., Dray-Spira R., Spire B., Castagna A., Mussini C., Zangerle R., Hessamfar M., Anderson J., Hamouda O., Ehren K., Obel N., Kirk O., Antinori A., Girardi E., Saracino A., Calmy A., Wit S., Wittkop L., Bucher C., Montoliu A., Raben D., Prins M., Meyer L., Chene G., Burns F., Amo J., Judd A., Warszawski J., Dabis F., Krause M., Ghosn J., Leport C., Reiss P., Wit F., Bucher H., Gibb D., Fatkenheuer G., Thorne C., Stephan C., Perez-Hoyos S., Bartmeyer B., Chkhartishvili N., Noguera-Julian A., Monforte A., Brockmeyer N., Prieto L., Conejo P., Soriano-Arandes A., Battegay M., Kouyos R., Tookey P., Casabona J., Miro J., Konopnick D., Goetghebuer T., Sonnerborg A., Torti C., Sabin C., Teira R., Garrido M., Haerry D., Miro M., Costagliola D., d'Arminio-Monforte A., Barger D., Schwimmer C., Termote M., Campbell M., Frederiksen C. M., Friis-Moller N., Kjaer J., Brandt R., Berenguer J., Bohlius J., Bouteloup V., Cozzi-Lepri A., Davies M. -A., Dorrucci M., Dunn D., Egger M., Furrer H., Guiguet M., Grabar S., Lambotte O., Leroy V., Lodi S., Matheron S., Nakagawa F., Paredes R., Phillips A., Puoti M., Rohner E., Schomaker M., Smit C., Sterne J., Thiebaut R., Valk M., Monge, S, Mocroft, A, Sabin, A, Touloumi, G, Sighem, A, Abgrall, S, Dray-Spira, R, Spire, B, Castagna, A, Mussini, C, Zangerle, R, Hessamfar, M, Anderson, J, Hamouda, O, Ehren, K, Obel, N, Kirk, O, Antinori, A, Girardi, E, Saracino, A, Calmy, A, Wit, S, Wittkop, L, Bucher, C, Montoliu, A, Raben, D, Prins, M, Meyer, L, Chene, G, Burns, F, Amo, J, Judd, A, Warszawski, J, Dabis, F, Krause, M, Ghosn, J, Leport, C, Reiss, P, Wit, F, Bucher, H, Gibb, D, Fatkenheuer, G, Thorne, C, Stephan, C, Perez-Hoyos, S, Bartmeyer, B, Chkhartishvili, N, Noguera-Julian, A, Monforte, A, Brockmeyer, N, Prieto, L, Conejo, P, Soriano-Arandes, A, Battegay, M, Kouyos, R, Tookey, P, Casabona, J, Miro, J, Konopnick, D, Goetghebuer, T, Sonnerborg, A, Torti, C, Sabin, C, Teira, R, Garrido, M, Haerry, D, Miro, M, Costagliola, D, d'Arminio-Monforte, A, Barger, D, Schwimmer, C, Termote, M, Campbell, M, Frederiksen, C, Friis-Moller, N, Kjaer, J, Brandt, R, Berenguer, J, Bohlius, J, Bouteloup, V, Cozzi-Lepri, A, Davies, M, Dorrucci, M, Dunn, D, Egger, M, Furrer, H, Guiguet, M, Grabar, S, Lambotte, O, Leroy, V, Lodi, S, Matheron, S, Nakagawa, F, Paredes, R, Phillips, A, Puoti, M, Rohner, E, Schomaker, M, Smit, C, Sterne, J, Thiebaut, R, Valk, M, Monge S., Mocroft A., Sabin A., Touloumi G., Sighem A., Abgrall S., Dray-Spira R., Spire B., Castagna A., Mussini C., Zangerle R., Hessamfar M., Anderson J., Hamouda O., Ehren K., Obel N., Kirk O., Antinori A., Girardi E., Saracino A., Calmy A., Wit S., Wittkop L., Bucher C., Montoliu A., Raben D., Prins M., Meyer L., Chene G., Burns F., Amo J., Judd A., Warszawski J., Dabis F., Krause M., Ghosn J., Leport C., Reiss P., Wit F., Bucher H., Gibb D., Fatkenheuer G., Thorne C., Stephan C., Perez-Hoyos S., Bartmeyer B., Chkhartishvili N., Noguera-Julian A., Monforte A., Brockmeyer N., Prieto L., Conejo P., Soriano-Arandes A., Battegay M., Kouyos R., Tookey P., Casabona J., Miro J., Konopnick D., Goetghebuer T., Sonnerborg A., Torti C., Sabin C., Teira R., Garrido M., Haerry D., Miro M., Costagliola D., d'Arminio-Monforte A., Barger D., Schwimmer C., Termote M., Campbell M., Frederiksen C. M., Friis-Moller N., Kjaer J., Brandt R., Berenguer J., Bohlius J., Bouteloup V., Cozzi-Lepri A., Davies M. -A., Dorrucci M., Dunn D., Egger M., Furrer H., Guiguet M., Grabar S., Lambotte O., Leroy V., Lodi S., Matheron S., Nakagawa F., Paredes R., Phillips A., Puoti M., Rohner E., Schomaker M., Smit C., Sterne J., Thiebaut R., and Valk M.

Abstract

Objectives: The aim of the study was to evaluate differences in immunovirological response to combination antiretroviral therapy (cART) in migrant and native men and women within a European collaboration of HIV cohorts Collaboration of Observational HIV Epidemiological Research in Europ (COHERE) in EuroCoord, 2004–2013. Methods: Migrants were defined as those with geographical origin (GO) different from the reporting country and were grouped as originating from Western Europe and Western Countries (WEWC), Eastern Europe (EE), North Africa and the Middle East (NAME), sub-Saharan Africa (SSA), Latin America (LA), Caribbean (CRB) and Asia/Oceania (ASIA/OCE). Native (NAT) individuals were defined as those originating from the reporting country. CD4 cell counts were modelled using piecewise linear mixed-effects models with two slopes, whereas models to estimate subdistribution hazard ratios (sHRs) were used for time to virological response (VR) (i.e. time from cART initiation to the first of two successive HIV RNA measurements < 400 HIV-1 RNA copies/ml). Results: Of 32 817 individuals, 25 799 (78.6%) were men. The percentage of migrants was higher in women (48.9%) than in men (21.2%) and migrants from SSA accounted for the largest migrant group (29.9% in men and 63.3% in women). Migrant men and women from SSA started at lower CD4 cell counts than NAT individuals, which remained lower over time. VR was ≥ 85% at 12 months for all groups except CRB women (77.7%). Compared with NAT men and women, lower VR was experienced by NAME [sHR 0.91; 95% confidence interval (CI) 0.86–0.97] and SSA (sHR 0.88; 95% CI 0.82–0.95) men and CRB (sHR 0.77; 85% CI 0.67–0.89) women, respectively. Conclusions: Immunovirological response to cART in Western Europe varies by GO and sex of patients. ART benefits are not equal for all, underlining the point that efforts need to prioritize those most in need.

Published
2018

35. Prevalence and Clinical Outcomes of Poor Immune Response Despite Virologically Suppressive Antiretroviral Therapy Among Children and Adolescents With Human Immunodeficiency Virus in Europe and Thailand: Cohort Study

Author

Smit C, Marques L, Klein N, Gulllen S, Judd A, Thorne C, Goodall R, Konigs C, Spoulou V, Prata F, Goetghebuer T, Chiappini E, Galli L, Naver L, Giaquinto C, Gibb D, Marczynska M, Okhonskaia L, Klimkait T, Lallernant M, Ngo-Giang-Huong N, Kiseleva G, Malyuta R, Volokha A, and European Pregnancy Paediat HIV Coh

Subjects
viral suppression, children, antiretroviral therapy, HIV, poor immune response
Abstract

Background. In human immunodeficiency virus (HIV)-positive adults, low CD4 cell counts despite fully suppressed HIV-1 RNA on antiretroviral therapy (ART) have been associated with increased risk of morbidity and mortality. We assessed the prevalence and outcomes of poor immune response (PIR) in children receiving suppressive ART. Methods. Sixteen cohorts from the European Pregnancy and Paediatric HIV Cohort Collaboration (EPPICC) contributed data. Children = 400 copies/mL) for >= 1 year were included. The prevalence of PIR (defined as World Health Organization advanced/severe immunosuppression for age) at 1 year of VS was described. Factors associated with PIR were assessed using logistic regression. Rates of acquired immunodeficiency syndrome (AIDS) or death on suppressive ART were calculated by PIR status. Results. Of 2318 children included, median age was 6.4 years and 68% had advanced/severe immunosuppression at ART initiation. At 1 year of VS, 12% had PIR. In multivariable analysis, PIR was associated with older age and worse immunological stage at ART start, hepatitis B coinfection, and residing in Thailand (all P=.03). Rates of AIDS/death (95% confidence interval) per 100 000 person-years were 1052 (547, 2022) among PIR versus 261 (166, 409) among immune responders; rate ratio of 4.04 (1.83, 8.92; P

Published
2020

37. Factors Associated With Nonadherence to Antiretroviral Therapy Among Young People Living With Perinatally Acquired HIV in England

Author

Judd, A, Melvin, D, Thompson, L. C, Foster, C, Le Prevost, M, Evangeli, M, Winston, A, Arenas-Pinto, A, Sturgeon, K, Rowson, Katie, Gibb, D. M, Castro, H, Judd, A, Melvin, D, Thompson, L. C, Foster, C, Le Prevost, M, Evangeli, M, Winston, A, Arenas-Pinto, A, Sturgeon, K, Rowson, Katie, Gibb, D. M, and Castro, H

Abstract

Young people living with perinatally acquired HIV may be at risk of poor adherence to antiretroviral therapy; identification of predictors, using a conceptual framework approach proposed previously by others, is important to identify those at higher risk. In 261 young people with perinatally acquired HIV in England, 70 (27%) reported 3-day nonadherence, 82 (31%) last month nonadherence, and 106 (41%) nonadherence on either measure. Of those reporting nonadherence on both measures, 52% (23/44) had viral load of ,50 copies/ml, compared with 88% (127/145) of those reported being fully adherent. In multivariable analysis, young person and medication theme factors were associated with nonadherence. The main predictors of 3-day nonadherence were antiretroviral therapy containing a boosted protease inhibitor and poorer quality of life. Predictors of last month nonadherence were having told more people about one’s HIV status, worse self-perception about having HIV, and boosted protease inhibitor–based regimens. The consistency of individual young person and medication factors in predicting nonadherence gives insight into where interventions may best be targeted to improve adherence.

Published
2020

38. Lessons for test and treat in an antiretroviral programme after decentralisation in Uganda: a retrospective analysis of outcomes in public healthcare facilities within the Lablite project

Author

Kiwuwa-Muyingo, S, Abongomera, George, Mambule, I, Senjovu, D, Katabira, E, Kityo, C, Gibb, D M, Ford, D, Seeley, J, Kiwuwa-Muyingo, S, Abongomera, George, Mambule, I, Senjovu, D, Katabira, E, Kityo, C, Gibb, D M, Ford, D, and Seeley, J

Abstract

Background We describe the decentralisation of antiretroviral therapy (ART) alongside Option B+ roll-out in public healthcare facilities in the Lablite project in Uganda. Lessons learned will inform programmes now implementing universal test and treat (UTT). Methods Routine data were retrospectively extracted from ART registers between October 2012 and March 2015 for all adults and children initiating ART at two primary care facilities (spokes) and their corresponding district hospitals (hubs) in northern and central Uganda. We describe ART initiation over time and retention and use of Cox models to explore risk factors for attrition due to mortality and loss to follow-up. Results from tracing of patients lost to follow-up were used to correct retention estimates. Results Of 2100 ART initiations, 1125 were in the north, including 944 (84%) at the hub and 181 (16%) at the spokes; children comprised 95 (10%) initiations at the hubs and 14 (8%) at the spokes. Corresponding numbers were 642 (66%) at the hub and 333 (34%) at the spokes in the central region (77 [12%] and 22 [7%], respectively, in children). Children <3 y of age comprised the minority of initiations in children at all sites. Twenty-three percent of adult ART initiations at the north hub were Option B+ compared with 45% at the spokes (25% and 65%, respectively, in the central region). Proportions retained in care in the north hub at 6 and 12 mo were 92% (95% CI 90 to 93) and 89% (895% CI 7 to 91), respectively. Corresponding corrected estimates in the north spokes were 87% (95% CI 78 to 93) and 82% (95% CI 72 to 89), respectively. In the central hub, corrected estimates were 84% (95% CI 80 to 87) and 78% (95% CI 74 to 82), and were 89% (95% CI 77.9 to 95.1) and 83% (95% CI 64.1 to 92.9) at the spokes, respectively. Among adults newly initiating ART, being older was independently associated with a lower risk of attrition (adjusted hazard ratio [aHR] 0.93 per 5 y [95% CI 0.88 to 0.97]). Other independent ris

Published
2020

42. Global temporal changes in the proportion of children with advanced disease at the start of combination antiretroviral therapy in an era of changing criteria for treatment initiation

Author

Panayidou K., Davies M. -A., Anderegg N., Egger M., Fatti G., Vinikoor M., Sawry S., Ehmer J., Eley B., Phiri S., Technau K. -G. u. N., Chimbetete C., Rabie H., Boulle A., Tanser F., Wood R., Wools-Kaloustian K., Vreeman R., Oyaro P., Ayaya S., Nakigozi G., Musick B., Yiannoutsos C., Amorissani-Folquet M., Takassi E., Sylla M., Renner L., Malateste K., Desmonde S., Leroy V., Kurniati N., Hansudewechakul R., Nguyen L. V., Ly P. S., Truong K. H., Kariminia A., Sohn A. H., Edmonds A., Yumo H. A., Dusingize J. C., Yotebieng M., Judd A., Rojo P., Smit C., Grabar S., Warszwarski J., Chene G., Raban D., Patel K., Seage G. R., Van Dyke R. B., Oleske J., Williams P. L., Abzug M. J., Succi R., Machado D. M., Pinto J., Rouzier V., Luque M., Mejia F., Khol V., Tucker J., Kumarasamy N., Saghayam S., Chandrasekaran E., Wati D. K., Vedaswari D., Malino I. Y., Muktiarti D., Fong S. M., Lim M., Daut F., Nik Yusoff N. K., Mohamad P., Mohamed T. J., Drawis M. R., Nallusamy R., Chan K. C., Sudjaritruk T., Sirisanthana V., Aurpibul L., Oberdorfer P., Denjanta S., Watanaporn S., Kongphonoi A., Lumbiganon P., Kosalaraksa P., Tharnprisan P., Udomphanit T., Jourdain G., Puthanakit T., Anugulruengkitt S., Phadungphon C., Chokephaibulkit K., Lapphra K., Phongsamart W., Sricharoenchai S., Du Q. T., Nguyen C. H., Do V. C., Ha T. M., An V. T., Khu D. T. K., Pham A. N., Nguyen L. T., Le O. N., Ross J. L., Sethaputra C., Law M. G., Cahn P., Cesar C., Fink V., Sued O., Dell'isola E., Perez H., Valiente J., Yamamoto C., Grinsztejn B., Veloso V., Luz P., de Boni R., Wagner S. C., Friedman R., Moreira R., Ferreira F., Maia M., de Menezes Succi R. C., Barbosa Gouv E A A. F. a. T., Wolff M., Cortes C., Rodriguez M. F., Allendes G., Pape J. W., Marcelin A., Perodin C., Luque M. T., Padgett D., Madero J. S., Ramirez B. C., Belaunzaran P., Vega Y. C., Gotuzzo E., Carriquiry G., McGowan C. C., Shepherd B. E., Sterling T., Jayathilake K., Person A. K., Rebeiro P. F., Giganti M., Castilho J., Duda S. N., Maruri F., Vansell H., P E Lagie N., Gateretse P., Munezero J., Nitereka V., Niyongabo T., Twizere C., Bukuru H., Nahimana T., Biziragusenyuka J., Manyundo R. S., Atsu K., Mbuh T., Ajeh R., Benwi M., Dzudie A., Mbuh A., Ngamani M. L., Nkome V., Amadou D., Ngassam E., Pefura Yone E. W., Ewanoge A. N., Fuhngwa N., Moki C., Akele C., Kitetele F., Lelo P., Tabala M., Okitolonda E. W., Wenzi L., Diafouka M., Ekat M. H., Nsonde D. M., Mafou A., Ntarambirwa F., Tuyishimire Y., Hakizimana T., Ayinkamiye J., Mukantwali S., Kayitesi H., Uwamahoro O., Habumuremyi V., Mukamana J., Kubwimana G., Mugenzi P., Muhoza B., Munyaneza A., Ndahiro E., Nyiransabimana D., D'Amour Sinayobye J., Sugira V., Benekigeri C., Mbaraga G., Adedimeji A., Anastos K., Dilorenzo M., Murchison L., Ross J., Addison D., Baker M., Brazier E., Jones H., Kelvin E., Kulkarni S., Nash D., Tymejczyk O., Elul B., Cai X., Hoover D., Kim H. -Y., Li C., Shi Q., Lancaster K., Kuniholm M., Parcesepe A., Duda S., Kimmel A., McNairy M., Diero L., Plus A. M. P. A. T. H., Bukusi E., Ssali J., Nalugoda F., Somi G. R., Lyamuya R. E., Ngonyani K., Lugina E., Urassa M., Michael D., Zannou M. D., Poda A., Sarfo F. S., Messou E., Chenal H., Minga K. A., Bissagnene E., Tanon A., Seydi M., Patassi A. A., Koumakpai-Adeothy S. A., Renner L. A., N'gbeche S. M., Bosse C. A., Kouakou K., Folquet M. A., Eboua F. c. O. T., Traore F. D., Dabis F. c. O., Arrive E., Balestre E., Becquet R., Bernard C., Arikawa S. C., Doring A., Jaquet A., Rabourdin E., Tiendrebeogo T., Jesson J., Ekouevi D. K., Azani J. -C., Coffi E P., Gnepa G., Kouadio C. G. K., Tchounga B., Maartens G., Lettow M. V., Muhairwe J., Jores A., Kamenova K., Fox M. P., Prozesky H., Zangerle R., Touloumi G., Warszawski J., Meyer L., Krause M. M., Ghosn J., Leport C., Wittkop L., Reiss P., Wit F., Prins M., Bucher H., Gibb D., Fatkenheuer G., Del Amo J., Obel N., Thorne C., Mocroft A., Kirk O., Stephan C., Perez-Hoyos S., Hamouda O., Bartmeyer B., Chkhartishvili N., Noguera-Julian A., Antinori A., D'Arminio Monforte A., Brockmeyer N., Prieto L., Conejo P. R., Soriano-Arandes A., Battegay M., Kouyos R., Mussini C., Tookey P., Casabona J., Miro J. M., Castagna A., Konopnick D., Goetghebuer T., Sonnerborg A., Torti C., Sabin C., Teira R., Garrido M., Haerry D., de Wit S., Costagliola D., Raben D., Barger D., Schwimmer C., Termote M., Campbell M., Frederiksen C. M., Friis-Moller N., Kjaer J., Brandt R. S., Berenguer J., Bohlius J., Bouteloup V., Cozzi-Lepri A., Dorrucci M., Dunn D., Furrer H., Guiguet M., Lambotte O., Lodi S., Matheron S., Miro J. M. ª., Monge S., Nakagawa F., Paredes R., Phillips A., Puoti M., Rohner E., Schomaker M., Sterne J., Thiebaut R., van der Valk M., Hazra R., Heckman B., O'gara E., Siminski S., Panayidou, K, Davies, M, Anderegg, N, Egger, M, Fatti, G, Vinikoor, M, Sawry, S, Ehmer, J, Eley, B, Phiri, S, Technau, K, Chimbetete, C, Rabie, H, Boulle, A, Tanser, F, Wood, R, Wools-Kaloustian, K, Vreeman, R, Oyaro, P, Ayaya, S, Nakigozi, G, Musick, B, Yiannoutsos, C, Amorissani-Folquet, M, Takassi, E, Sylla, M, Renner, L, Malateste, K, Desmonde, S, Leroy, V, Kurniati, N, Hansudewechakul, R, Nguyen, L, Ly, P, Truong, K, Kariminia, A, Sohn, A, Edmonds, A, Yumo, H, Dusingize, J, Yotebieng, M, Judd, A, Rojo, P, Smit, C, Grabar, S, Warszwarski, J, Chene, G, Raban, D, Patel, K, Seage, G, Van Dyke, R, Oleske, J, Williams, P, Abzug, M, Succi, R, Machado, D, Pinto, J, Rouzier, V, Luque, M, Mejia, F, Khol, V, Tucker, J, Kumarasamy, N, Saghayam, S, Chandrasekaran, E, Wati, D, Vedaswari, D, Malino, I, Muktiarti, D, Fong, S, Lim, M, Daut, F, Nik Yusoff, N, Mohamad, P, Mohamed, T, Drawis, M, Nallusamy, R, Chan, K, Sudjaritruk, T, Sirisanthana, V, Aurpibul, L, Oberdorfer, P, Denjanta, S, Watanaporn, S, Kongphonoi, A, Lumbiganon, P, Kosalaraksa, P, Tharnprisan, P, Udomphanit, T, Jourdain, G, Puthanakit, T, Anugulruengkitt, S, Phadungphon, C, Chokephaibulkit, K, Lapphra, K, Phongsamart, W, Sricharoenchai, S, Du, Q, Nguyen, C, Do, V, Ha, T, An, V, Khu, D, Pham, A, Le, O, Ross, J, Sethaputra, C, Law, M, Cahn, P, Cesar, C, Fink, V, Sued, O, Dell'Isola, E, Perez, H, Valiente, J, Yamamoto, C, Grinsztejn, B, Veloso, V, Luz, P, de Boni, R, Wagner, S, Friedman, R, Moreira, R, Ferreira, F, Maia, M, de Menezes Succi, R, Barbosa Gouv E A, A, Wolff, M, Cortes, C, Rodriguez, M, Allendes, G, Pape, J, Marcelin, A, Perodin, C, Padgett, D, Madero, J, Ramirez, B, Belaunzaran, P, Vega, Y, Gotuzzo, E, Carriquiry, G, Mcgowan, C, Shepherd, B, Sterling, T, Jayathilake, K, Person, A, Rebeiro, P, Giganti, M, Castilho, J, Duda, S, Maruri, F, Vansell, H, P E Lagie, N, Gateretse, P, Munezero, J, Nitereka, V, Niyongabo, T, Twizere, C, Bukuru, H, Nahimana, T, Biziragusenyuka, J, Manyundo, R, Atsu, K, Mbuh, T, Ajeh, R, Benwi, M, Dzudie, A, Mbuh, A, Ngamani, M, Nkome, V, Amadou, D, Ngassam, E, Pefura Yone, E, Ewanoge, A, Fuhngwa, N, Moki, C, Akele, C, Kitetele, F, Lelo, P, Tabala, M, Okitolonda, E, Wenzi, L, Diafouka, M, Ekat, M, Nsonde, D, Mafou, A, Ntarambirwa, F, Tuyishimire, Y, Hakizimana, T, Ayinkamiye, J, Mukantwali, S, Kayitesi, H, Uwamahoro, O, Habumuremyi, V, Mukamana, J, Kubwimana, G, Mugenzi, P, Muhoza, B, Munyaneza, A, Ndahiro, E, Nyiransabimana, D, D'Amour Sinayobye, J, Sugira, V, Benekigeri, C, Mbaraga, G, Adedimeji, A, Anastos, K, Dilorenzo, M, Murchison, L, Addison, D, Baker, M, Brazier, E, Jones, H, Kelvin, E, Kulkarni, S, Nash, D, Tymejczyk, O, Elul, B, Cai, X, Hoover, D, Kim, H, Li, C, Shi, Q, Lancaster, K, Kuniholm, M, Parcesepe, A, Kimmel, A, Mcnairy, M, Diero, L, Plus, A, Bukusi, E, Ssali, J, Nalugoda, F, Somi, G, Lyamuya, R, Ngonyani, K, Lugina, E, Urassa, M, Michael, D, Zannou, M, Poda, A, Sarfo, F, Messou, E, Chenal, H, Minga, K, Bissagnene, E, Tanon, A, Seydi, M, Patassi, A, Koumakpai-Adeothy, S, N'Gbeche, S, Bosse, C, Kouakou, K, Folquet, M, Eboua, F, Traore, F, Dabis, F, Arrive, E, Balestre, E, Becquet, R, Bernard, C, Arikawa, S, Doring, A, Jaquet, A, Rabourdin, E, Tiendrebeogo, T, Jesson, J, Ekouevi, D, Azani, J, Coffi E, P, Gnepa, G, Kouadio, C, Tchounga, B, Maartens, G, Lettow, M, Muhairwe, J, Jores, A, Kamenova, K, Fox, M, Prozesky, H, Zangerle, R, Touloumi, G, Warszawski, J, Meyer, L, Krause, M, Ghosn, J, Leport, C, Wittkop, L, Reiss, P, Wit, F, Prins, M, Bucher, H, Gibb, D, Fatkenheuer, G, Del Amo, J, Obel, N, Thorne, C, Mocroft, A, Kirk, O, Stephan, C, Perez-Hoyos, S, Hamouda, O, Bartmeyer, B, Chkhartishvili, N, Noguera-Julian, A, Antinori, A, D'Arminio Monforte, A, Brockmeyer, N, Prieto, L, Conejo, P, Soriano-Arandes, A, Battegay, M, Kouyos, R, Mussini, C, Tookey, P, Casabona, J, Miro, J, Castagna, A, Konopnick, D, Goetghebuer, T, Sonnerborg, A, Torti, C, Sabin, C, Teira, R, Garrido, M, Haerry, D, de Wit, S, Costagliola, D, Raben, D, Barger, D, Schwimmer, C, Termote, M, Campbell, M, Frederiksen, C, Friis-Moller, N, Kjaer, J, Brandt, R, Berenguer, J, Bohlius, J, Bouteloup, V, Cozzi-Lepri, A, Dorrucci, M, Dunn, D, Furrer, H, Guiguet, M, Lambotte, O, Lodi, S, Matheron, S, Monge, S, Nakagawa, F, Paredes, R, Phillips, A, Puoti, M, Rohner, E, Schomaker, M, Sterne, J, Thiebaut, R, van der Valk, M, Hazra, R, Heckman, B, O'Gara, E, and Siminski, S

Subjects
0301 basic medicine, Male, sub-Saharan Africa, Databases, Factual, CD4 cell count, HIV Infections, Global Health, Cohort Studies, 0302 clinical medicine, Central and South America, Advanced disease, Medicine, 030212 general & internal medicine, Prospective Studies, Cd4 cell count, skin and connective tissue diseases, Child, Research Articles, humanities, 3. Good health, Europe, Infectious Diseases, Child, Preschool, Income, Drug Therapy, Combination, Female, advanced HIV disease, antiretroviral therapy, Asia, Caribbean, North America, WHO guidelines, Adolescent, Adult, Anti-HIV Agents, CD4 Lymphocyte Count, Drug Administration Schedule, Follow-Up Studies, Humans, Poverty, World Health Organization, Research Article, medicine.medical_specialty, education, 610 Medicine & health, 03 medical and health sciences, Acquired immunodeficiency syndrome (AIDS), 360 Social problems & social services, Intensive care medicine, business.industry, Public Health, Environmental and Occupational Health, medicine.disease, 030112 virology, Antiretroviral therapy, Who guidelines, sense organs, business, sub‐Saharan Africa
Abstract

Introduction: The CD4 cell count and percent at initiation of combination antiretroviral therapy (cART) are measures of advanced HIV disease and thus are important indicators of programme performance for children living with HIV. In particular, World Health Organization (WHO) 2017 guidelines on advanced HIV disease noted that >80% of children aged 40% of children in low- and middle-income countries started cART with severe immunodeficiency compared to

Published
2018

43. Uterine activity in labour

Author

Gibb, D. M. F.

Subjects
618
Abstract

Reproductive success, the birth of a healthy child, may be seen in mechanical terms as the uncomplicated filling, enlargement and subsequent emptying of the uterus: a quite remarkable organ. Much clinical activity by obstetricians concerns the need to prevent premature emptying of the uterus and in turn causing it to expel the fetus at the appropriate time. Many believe a successful conclusion preferably includes the expulsion of the fetus safely per via naturales. Currently concern is expressed in many countries about the increasing frequency of Caesarean birth. An understanding of uterine activity is important for effective management of several pregnancy complications. However, this thesis is restricted to the birth process itself: the intra partum period. Several investigations have documented uterine activity at various times. However, detailed analysis correlated with the various phases of labour had not been undertaken. Previous workers had omitted to study normal events before abnormal ones effectively working without a normal range. The progress of labour has to be understood within the context of the nature of its onset and subsequent documentation of dilatation of the uterine cervix on a partogram: a graphic representation of labour. Preliminary work was undertaken to clarify types of labour progress and subsequent outcome of the labour according to the cervical dilatation pattern (cervimetric progress). The next step complemented this with a study of intrauterine pressure changes and the evolution adequately undertaken bearing in mind the important variables of parity and actual cervical dilatation at the time. Uterine activity profiles during labour were generated and significant differences shown according to parity. Induced labour was then studied documenting comparative profiles and the cumulative uterine activity as labour progressed. This led to the development of the concept of the total uterine activity in labour reflecting the resistance to the fetus passing through the birth canal: the cervical and pelvic tissue resistance. These results may be applied in the rational management of difficult labours permitting the appropriate use of oxytocic drugs and providing the data to determine the appropriate use of Caesarean delivery.

Published
1988

44. Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand

Author

Goetghebuer T, Hainaut M, Van der Kelen E, Delforge M, Warszawski J, Le Chenadec J, Ramos E, Dialla O, Wack T, Laurent C, Selmi L, Leymarie I, Benali F, Brossard M, Boufassa L, Floch-Tudal C, Firtion G, Hau I, Chace A, Bolot P, Blanche S, Granier M, Labrune P, Lachassine E, Dollfus C, Levine M, Fourcade C, Heller-Roussin B, Runel-Belliard C, Tricoire J, Monpoux F, Chirouze C, Reliquet V, Brouard J, Kebaili K, Fialaire P, Lalande M, Mazingue F, Partisani M, Koenigs C, Schultze-Strasser S, Baumann U, Niehues T, Neubert J, Kobbe R, Feiterna-Sperling C, Buchholz B, Notheis G, Spoulou V, Tovo P, Galli L, Chiappini E, Patrizia O, Larovere D, Ruggeri M, Faldella G, Baldi F, Badolato R, Montagnani C, Venturini E, Lisi C, Di Biagio A, Taramasso L, Giacomet V, Erba P, Esposito S, Lipreri R, Salvini F, Tagliabue C, Cellini M, Bruzzese E, Lo Vecchio A, Rampon O, Dona D, Romano A, Dodi I, Maccabruni A, Consolini R, Bernardi S, Genovese O, Olmeo P, Cristiano L, Mazza A, Garazzino S, Pellegatta A, Pajkrt D, Scherpbier H, Weijsenfeld A, van der Plas A, Jurriaans S, Back N, Zaaijer H, Berkhout B, Cornelissen M, Schinkel C, Wolthers K, Fraaij P, van Rossum A, van der Knaap L, Visser E, Boucher C, Koopmans M, van Kampen J, Pas S, Henriet S, de Flier M, van Aerde K, Strik-Albers R, Rahamat-Langendoen J, Stelma F, Scholvinck E, de Groot-de Jonge H, Niesters H, van Leer-Buter C, Knoester M, Bont L, Geelen S, Wolfs T, Nauta N, Ang C, van Houdt R, Pettersson A, Vandenbroucke-Grauls C, Reiss P, Bezemer D, van Sighem A, Smit C, Wit F, Boender T, Zaheri S, Hillebregt M, de Jong A, Bergsma D, Grivell S, Jansen A, Raethke M, Meijering R, de Groot L, van den Akker M, Bakker Y, Claessen E, El Berkaoui A, Koops J, Kruijne E, Lodewijk C, Munjishvili L, Peeck B, Ree C, Regtop R, Ruijs Y, Rutkens T, Schoorl M, Timmerman A, Tuijn E, Veenenberg L, van der Vliet S, Wisse A, Woudstra T, Tuk B, Marczynska M, Oldakowska A, Popielska J, Coupland U, Doroba M, Marques L, Teixeira C, Fernandes A, Prata F, Ene L, Gingaras C, Radoi R, Okhonskaia L, Voronin E, Miloenko M, Labutina S, Soler-Palacin P, Antoinette Frick M, Perez-Hoyos S, Mur A, Lopez N, Mendez M, Mayol L, Vallmanya T, Calavia O, Garcia L, Coll M, Pineda V, Rius N, Rovira N, Duenas J, Fortuny C, Noguera-Julian A, Jose Mellado M, Escosa L, Garcia Hortelano M, Sainz T, Isabel Gonzalez-Tome M, Rojo P, Blazquez D, Tomas Ramos J, Prieto L, Guillen S, Luisa Navarro M, Saavedra J, Santos M, Angeles Munoz M, Ruiz B, Fernandez Mc Phee C, Jimenez de Ory S, Alvarez S, Angel Roa M, Beceiro J, Martinez J, Badillo K, Apilanez M, Pocheville I, Garrote E, Colino E, Gomez Sirvent J, Garzon M, Roman V, Montesdeoca A, Mateo M, Jose Munoz M, Angulo R, Neth O, Falcon L, Terol P, Luis Santos J, Moreno D, Lendinez F, Grande A, Jose Romero F, Perez C, Lillo M, Losada B, Herranz M, Bustillo M, Guerrero C, Collado P, Antonio Couceiro J, Perez A, Isabel Piqueras A, Breton R, Segarra I, Gavilan C, Jareno E, Montesinos E, Dapena M, Alvarez C, Gloria Andres A, Marugan V, Ochoa C, Alfayate S, Isabel Menasalvas A, de Miguel E, Naver L, Soeria-Atmadja S, Hagas V, Aebi-Popp K, Asner S, Aubert V, Battegay M, Baumann M, Bernasconi E, Boni J, Brazzola P, Bucher H, Calmy A, Cavassini M, Ciuffi A, Duppenthaler A, Dollenmaier G, Egger M, Elzi L, Fehr J, Fellay J, Francini K, Furrer H, Fux C, Grawe C, Gunthard H, Haerry D, Hasse B, Hirsch H, Hoffmann M, Hosli I, Kahlert C, Kaiser L, Keiser O, Klimkait T, Kovari H, Kouyos R, Ledergerber B, Martinetti G, de Tejada M, Metzner K, Muller, Nicca D, Paioni P, Pantaleo G, Polli C, Posfay-Barbe K, Rauch A, Rudin C, Schmid P, Scherrer A, Speck R, Tarr P, Lecompte T, Trkola A, Vernazza P, Wagner N, Wandeler G, Weber R, Wyler C, Yerly S, Techakunakorn P, Prachanukroh C, Hansudewechakul R, Wanchaitanawong V, Theansavettrakul S, Nanta S, Ngampiyaskul C, Phanomcheong S, Hongsiriwon S, Karnchanamayul W, Chacheongsao B, Kwanchaipanich R, Kanjanavanit S, Prapinklao S, Kamonpakorn N, Nantarukchaikul M, Adulyadej B, Layangool P, Mekmullica J, Lucksanapisitkul P, Watanayothin S, Lertpienthum N, Warachit B, Hanpinitsak S, Potchalongsin S, Thanasiri P, Krikajornkitti S, Attavinijtrakarn P, Srirojana S, Bunjongpak S, Puangsombat A, Na-Rajsima S, Ananpatharachai P, Akarathum N, Phuket V, Lawtongkum W, Kheunjan P, Suriyaboon T, Saipanya A, Than-in-at K, Jaisieng N, Suaysod R, Chailoet S, Naratee N, Kawilapat S, Kaleeva T, Baryshnikova Y, Soloha S, Bashkatova N, Raus I, Glutshenko O, Ruban Z, Prymak N, Kiseleva G, Bailey H, Lyall H, Butler K, Doerholt K, Foster C, Klein N, Menson E, Riordan A, Shingadia D, Tudor-Williams G, Tookey P, Welch S, Collins I, Cook C, Dobson D, Fairbrother K, Gibb D, Judd A, Harper L, Parrott F, Tostevin A, Van Looy N, Walsh A, Scott S, Vaughan Y, Laycock N, Bernatoniene J, Finn A, Hutchison L, Sharpe G, Williams A, Lyall E, Seery P, Lewis P, Miles K, Subramaniam B, Hutchinson L, Ward P, Sloper K, Gopal G, Doherty C, Hague R, Price V, Bamford A, Bundy H, Clapson M, Flynn J, Novelli V, Ainsley-Walker P, Tovey P, Gurtin D, Garside J, Fall A, Porter D, Segal S, Ball C, Hawkins S, Chetcuti P, Dowie M, Bandi S, McCabe A, Eisenhut M, Handforth J, Roy P, Flood T, Pickering A, Liebeschuetz S, Kavanagh C, Murphy C, Rowson K, Tan T, Daniels J, Lees Y, Kerr E, Thompson F, Le Provost M, Cliffe L, Smyth A, Stafford S, Freeman A, Reddy T, Fidler K, Christie S, Gordon A, Rogahn D, Harris S, Collinson A, Jones L, Offerman B, Van Someren V, Benson C, Riddell A, O'Connor R, Brown N, Ibberson L, Shackley F, Faust S, Hancock J, Donaghy S, Prime K, Sharland M, Storey S, Gorman S, Monrose C, Walters S, Cross R, Broomhall J, Scott D, Stroobant J, Bridgwood A, McMaster P, Evans J, Gardiner T, Jones R, Gardiner K, European Pregnancy Paediat HIV Coh, Stichting HIV Monitoring, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Department of Sciences for Woman and Child's Health, Florence University, Dipartimento di Pediatria, Azienda Ospedaliera di Padova, Université Grenoble Alpes - UFR Pharmacie (UGA UFRP), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Pediatrics, and Virology

Subjects
Male, 0301 basic medicine, Time Factors, HIV, antiretroviral therapy, children, second-line, switch, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Drug Resistance, INFANTS, HIV Infections, Cohort Studies, chemistry.chemical_compound, 0302 clinical medicine, Interquartile range, Antiretroviral Therapy, Highly Active, ADOLESCENTS, Cumulative incidence, Viral, Treatment Failure, 030212 general & internal medicine, Child, ComputingMilieux_MISCELLANEOUS, Antiretroviral therapy, Children, Second-line, Switch, Age Factors, Anti-HIV Agents, Child, Preschool, Drug Resistance, Viral, Drug Substitution, Europe, Female, Humans, Infant, Reverse Transcriptase Inhibitors, Thailand, Viral Load, Reverse-transcriptase inhibitor, Immunosuppression, OPEN-LABEL, VIROLOGICAL FAILURE, 3. Good health, Infectious Diseases, Viral load, medicine.drug, Microbiology (medical), medicine.medical_specialty, Efavirenz, Nevirapine, SCALE-UP, Article, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Internal medicine, medicine, Highly Active, Preschool, business.industry, HIV-1 DRUG-RESISTANCE, ADULTS, 030112 virology, RANDOMIZED-TRIAL, Regimen, INFECTED CHILDREN, VIRAL LOAD, chemistry, business
Abstract

Background. Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand.Methods. Children aged = 2 nucleoside reverse transcriptase inhibitors p[NRTIs] plus nonnucleoside reverse transcriptase inhibitor p[NNRTI] or boosted protease inhibitor p[PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of >= 1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks.Results. Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch.Conclusions. One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch.

Published
2017

47. Cotrimoxazole or multi-mineral multi-vitamins to improve post-discharge outcomes following severe anaemia in African children: a randomised controlled trial

Author

Maitland, K, Olupot-Olupot, P, Kiguli, S, Chagaluka, G, Alaroker, F, Opoka, R, Mpoya, A, Walsh, K, Engoru, C, Nteziyaremye, J, Mallewa, M, Kennedy, N, Nakuya, M, Namayanja, C, Kayaga, J, Nabawanuka, E, Sennyondo, T, Aromut, D, Kumwenda, F, Williams Musika, C, Thomason, M, Bates, I, Boele Von Hensbroek, M, Evans, J, Uyoya, S, Williams, T, Frost, G, George, E, Gibb, D, Walker, A, Medical Research Council (MRC), Medical Research Council, Medical Research Council, UK, Imperial College Healthcare NHS Trust- BRC Funding, and Engineering & Physical Science Research Council (EPSRC)

Subjects
SPRINKLES, YOUNG-CHILDREN, Malawi, Science & Technology, IRON FORTIFICATION, MORTALITY, Infant, Anemia, PROPHYLAXIS, Patient Discharge, TRACT trial group, 1117 Public Health and Health Services, DEFICIENCY, DOUBLE-BLIND, MALARIA, TRANSFUSION, INFECTION, Dietary Supplements, Trimethoprim, Sulfamethoxazole Drug Combination, Humans, Uganda, Child, Life Sciences & Biomedicine, Public, Environmental & Occupational Health, 0605 Microbiology
Abstract

Background: Severe anaemia (haemoglobin0.2). By day180, 489(24%) MVMM vs 509(26%) iron/folate had experienced one or more SAEs (HR=0.95 (0.84- 1.07), p=0.40) and 500(25%) cotrimoxazole vs 498(25%) no cotrimoxazole (HR=1.01 (0.89,1.15) p=0.85). Most SAEs were readmissions, occurring in 692(17%) children (175(4%) with ≥2 readmissions). Interpretation: Neither enhanced supplementation with MVMM versus iron/folate treatment or cotrimoxazole prophylaxis improved 6-month survival. High rates of hospital re-admission suggest that novel interventions are urgently required for severe anaemia, given the burden it places on overstretched health services in Africa.

Published
2019

48. CD4 recovery following antiretroviral treatment interruptions in children and adolescents with HIV infection in Europe and Thailand

Author

Galli, L., Crichton, S., Buzzoni, C., Goetghebuer, T., Jourdain, G., Judd, A., Klein, N., José Mellado, M., Noguera-Julian, A., Kahlert, C., Spoulou, V., Scherpbier, H., Marques, L., Collins, I. J., Gibb, D. M., González Tome, M. I., Warszawski, J., Dollfus, C., Königs, C., Prata, F., Chiappini, E., Naver, L., Giaquinto, C., Thorne, C., Marczynska, M., Okhonskaia, L., Borkird, T., Attavinijtrakarn, P., Malyuta, R., Volokha, A., Ene, L., Goodall, R., Pediatric surgery, Paediatric Infectious Diseases / Rheumatology / Immunology, and AII - Infectious diseases

Subjects
Male, 0301 basic medicine, medicine.medical_specialty, paediatric, Younger age, Adolescent, Anti-HIV Agents, antiretroviral therapy, Human immunodeficiency virus (HIV), HIV Infections, medicine.disease_cause, Pediatrics, Drug Administration Schedule, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Internal medicine, Antiretroviral treatment, Humans, Medicine, Pharmacology (medical), 030212 general & internal medicine, Viral suppression, Limitació de l'esforç terapèutic, Child, Withholding treatment, Pediatria, business.industry, treatment interruption, Health Policy, Infant, Antiretrovirals, Thailand, 030112 virology, Antiretroviral therapy, Antiretroviral agents, Confidence interval, CD4 Lymphocyte Count, Europe, Treatment Outcome, Infectious Diseases, Child, Preschool, Regression Analysis, Drug Therapy, Combination, Female, business, Nadir (topography)
Abstract

Objectives: The aim of the study was to explore factors associated with CD4 percentage (CD4%) reconstitution following treatment interruptions (TIs) of antiretroviral therapy (ART). Methods: Data from paediatric HIV-infected cohorts across 17 countries in Europe and Thailand were pooled. Children on combination ART (cART; at least three drugs from at least two classes) for > 6 months before TI of ≥ 30 days while aged

Published
2019

49. CD4 recovery following antiretroviral treatment interruptions in children and adolescents with HIV infection in Europe and Thailand

Author

Galli, L. Crichton, S. Buzzoni, C. Goetghebuer, T. and Jourdain, G. Judd, A. Klein, N. Jose Mellado, M. and Noguera-Julian, A. Kahlert, C. R. Spoulou, V. Scherpbier, H. and Marques, L. Collins, I. J. Gibb, D. M. Gonzalez Tome, Mi and Warszawski, J. Dollfus, C. Koenigs, C. Prata, F. and Chiappini, E. Naver, L. Giaquinto, C. Thorne, C. and Marczynska, M. Okhonskaia, L. Borkird, T. Attavinijtrakarn, P. Malyuta, R. Volokha, A. Ene, L. Goodall, R. and European Pregnancy Paediat HIV

Abstract

Objectives The aim of the study was to explore factors associated with CD4 percentage (CD4%) reconstitution following treatment interruptions (TIs) of antiretroviral therapy (ART). Methods Data from paediatric HIV-infected cohorts across 17 countries in Europe and Thailand were pooled. Children on combination ART (cART; at least three drugs from at least two classes) for > 6 months before TI of >= 30 days while aged CD4% at restart of ART (r-ART) and in the long term (up to 24 months after r-ART) following the first TI was modelled using asymptotic regression. Results In 779 children with at least one TI, the median age at first TI was 10.1 [interquartile range (IQR) 6.4, 13.6] years and the mean CD4% was 27.3% [standard deviation (SD) 11.0%]; the median TI duration was 9.0 (IQR 3.5, 22.5) months. In regression analysis, the mean CD4% was 19.2% [95% confidence interval (CI) 18.3, 20.1%] at r-ART, and 27.1% (26.2, 27.9%) in the long term, with half this increase in the first 6 months. r-ART and long-term CD4% values were highest in female patients and in children aged TI. Long-term CD4% was highest in those with a TI lasting 1 to = 25% (all P < 0.001). The effect of CD4% nadir during the TI differed significantly (P = 0.038) by viral suppression at the start of the TI; in children with CD4% nadir TI, recovery was better in those virally suppressed prior to the TI; viral suppression was not associated with recovery in children with CD4% nadir >= 25%. Conclusions After restart of ART following TI, most children reconstituted well immunologically. Nevertheless, several factors predicted better immunological reconstitution, including younger age and higher nadir CD4% during TI.

Published
2019

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