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594 results on '"Maartens G"'

1. Impact of immune reconstitution inflammatory syndrome on antiretroviral therapy adherence

Author

Nachega JB, Morroni C, Chaisson RE, Goliath R, Efron A, Ram M, and Maartens G

Subjects
Medicine (General), R5-920
Abstract

Jean B Nachega,1,2,4 Chelsea Morroni,1 Richard E Chaisson,2–4 Rene Goliath,1 Anne Efron,4 Malathi Ram,2 Gary Maartens11University of Cape Town, Department of Medicine, Division of Clinical Pharmacology, Cape Town, South Africa; 2Johns Hopkins University, Bloomberg School of Public Health, Departments of International Health and Epidemiology, 3Johns Hopkins University, School of Medicine, Department of Medicine, Division of Infectious Diseases, 4Johns Hopkins University, Center for Tuberculosis Research, Baltimore, Maryland, USAObjective: We determined the impact of immune reconstitution inflammatory syndrome (IRIS) on antiretroviral therapy (ART) adherence in a cohort of 274 human immunodeficiency virus (HIV)-infected South African adults initiating ART.Methods: We carried out a secondary analysis of data from a randomized controlled trial of partially supervised ART in Cape Town, South Africa. Monthly pill count adherence, viral suppression (HIV viral load < 50 c/mL), and IRIS events were documented. Poisson regression was used to identify variables associated with ART adherence below the median in the first 6 months of ART.Results: We enrolled 274 patients: 58% women, median age 34 years, median CD4 count 98 cells/µL, 46% World Health Organization clinical stage IV, and 40% on treatment for tuberculosis (TB). IRIS and TB-IRIS developed in 8.4% and 6.6% of patients, respectively. The median cumulative adherence at 6 months for those with an IRIS event vs no IRIS was 95.5% vs 98.2% (P = 0.04). Although not statistically significant, patients developing IRIS had a lower 6-month viral load suppression than those without IRIS (68% vs 80%, P = 0.32). ART adherence below the median of 98% was independently associated with alcohol abuse (relative risk [RR] 1.5; 95% confidence interval [CI] 1.2–1.9; P = 0.003) and IRIS events (RR 1.7; 95% CI 1.2–2.2; P = 0.001).Conclusion: Although IRIS events were associated with slightly lower adherence rates, overall adherence to ART remained high in this study population. Concerns about IRIS should not deter clinicians from early ART initiation.Keywords: ART, adherence, TB, HIV/AIDS, IRIS

Published
2012

2. Outcome of AIDS-associated cryptococcal meningitis initially treated with 200 mg/day or 400 mg/day of fluconazole

Author

Morroni C, Meintjes GA, Schaars CF, Post FA, and Maartens G

Subjects
Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background AIDS-associated cryptococcal meningitis has a high mortality. Fluconazole was the only systemic antifungal therapy available in our centre. From 1999–2001 we used low-dose fluconazole (200 mg daily initially), and did not offer therapy to patients perceived to have poor prognoses. In 2001 donated fluconazole became available, allowing us to use standard doses (400 mg daily initially). Antiretroviral therapy was not available during the study period. Methods Retrospective chart review of adult patients before and after the fluconazole donation. Results 205 patients fulfilled the inclusion criteria, 77 before and 128 after the donation. Following the donation fewer patients received no antifungal treatment (5% vs 19%, p = 0.002), and more patients received standard-dose fluconazole (90% vs 6%, p < 0.001). In-hospital mortality was 25%. Impaired consciousness, no antifungal treatment received and cerebrospinal fluid antigen titre > 1,000 were independent predictors of in-hospital mortality. Concomitant rifampicin did not affect in-hospital survival. Thirteen patients were referred to the tertiary referral hospital and received initial treatment with amphotericin B for a mean of 6 days – their in-hospital survival was not different from patients who received only fluconazole (p = 0.9). Kaplan-Meier analysis showed no differences in length of survival by initial treatment with standard or low doses of fluconazole (p = 0.27 log rank test); median survival was 76 and 82 days respectively. Conclusion Outcome of AIDS-associated cryptococcal meningitis is similar with low or standard doses of fluconazole. The early mortality is high. Initial therapy with amphotericin B and other measures may be needed to improve outcome.

Published
2006
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3. Liver Injury in People With HIV on Antituberculosis and/or Antiretroviral Therapy—Assessing Causality Using the Updated Roussel Uclaf Causality Assessment Method.

Author

Gunter, H. M., Tatz, G., Maartens, G., Spearman, C. W., Mehta, U., and Cohen, K.

Abstract

Purpose: We compared performance of the Roussel Uclaf Causality Assessment Method (RUCAM) with multidisciplinary expert panel review in identifying a drug‐induced liver injury (DILI) due to antituberculosis therapy (ATT) and/or antiretroviral therapy (ART). Methods: Cases were drawn from a prospective registry of hospitalised adults with suspected DILI due to ATT and/or ART in Cape Town, South Africa. Participants had to fulfil American Thoracic Society criteria for ATT interruption (alanine transaminase [ALT] ≥5 times upper limit of normal [ULN]/ALT ≥3 times [ULN] and symptomatic). Causality assessment by expert panel review served as reference standard. The panel ranked potentially implicated drugs as certain, probable, possible or unlikely causes guided by World Health Organization Uppsala Monitoring Centre criteria. The RUCAM was performed for each potentially implicated drug. We calculated sensitivity and specificity of the RUCAM in identifying a probable/certain drug cause for liver injury. Results: We included 48 participants. All were people with HIV (PWH). Twenty‐seven were on concomitant ART and ATT, with a median of six potentially hepatotoxic drugs per case. Sensitivity and specificity of the RUCAM in identifying a probable/certain drug cause of liver injury compared with expert panel review was 7% and 100% respectively. Implicated drugs (times ranked probable/certain by panel) were isoniazid (18/0), pyrazinamide (17/0), rifampicin (15/1), efavirenz (6/4) and lopinavir/ritonavir (1/0). Conclusions: PWH with liver injury received multiple potentially implicated drugs, which may increase liver injury risk and complicate causality assessment. Compared with expert panel review, the RUCAM had low sensitivity in detecting probable or certain drug causes of liver injury. [ABSTRACT FROM AUTHOR]

Published
2024
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6. Optimizing Moxifloxacin Dose in MDR-TB Participants with or without Efavirenz Coadministration Using Population Pharmacokinetic Modeling

Author

Chirehwa, M. T., primary, Resendiz-Galvan, J. E., additional, Court, R., additional, De Kock, M., additional, Wiesner, L., additional, de Vries, N., additional, Harding, J., additional, Gumbo, T., additional, Warren, R., additional, Maartens, G., additional, Denti, P., additional, and McIlleron, H., additional

Published
2023
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7. Focused investigations to expedite cancer diagnosis among patients with lymphadenopathy in a tuberculosis- and HIV-endemic region

Author

Antel, Katherine, primary, Oosthuizen, Jenna, additional, Brown, Karryn, additional, Malherbe, F., additional, Loebenberg, P., additional, Seaton, Cylene, additional, Baloyi, S., additional, Simba, K., additional, Chetty, D., additional, Louw, V.J., additional, Maartens, G., additional, and Verburgh, E.R., additional

Published
2022
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8. Impact of Dolutegravir-Based Antiretroviral Therapy on Piperaquine Exposure following Dihydroartemisinin-Piperaquine Intermittent Preventive Treatment of Malaria in Pregnant Women Living with HIV

Author

Banda, CG, Nkosi, D, Allen, E, Workman, L, Madanitsa, M, Chirwa, M, Kapulula, M, Muyaya, S, Munharo, S, Tarning, J, Phiri, KS, Mwapasa, V, ter Kuile, FO, Maartens, G, and Barnes, KI

Subjects
Pharmacology, Infectious Diseases, Pharmacology (medical)
Abstract

Dihydroartemisinin-piperaquine, an artemisinin-based combination therapy, has been identified as a promising agent for intermittent preventive treatment of malaria in pregnancy. However, in pregnant women living with HIV (PLWH), efavirenz-based antiretroviral therapy (ART) significantly reduces the plasma exposure of piperaquine. In an open-label, nonrandomized, fixed-sequence, pharmacokinetic study, we compared piperaquine plasma concentrations in 13 pregnant women during a 3-day treatment course of dihydroartemisinin-piperaquine when coadministered with efavirenz-based versus dolutegravir-based ART in the second or third trimester of pregnancy. Piperaquine concentrations were measured over a 28-day period, while on efavirenz-based ART and after switching to dolutegravir-based ART. Noncompartmental analysis was performed, and geometric mean ratios (GMRs) and 90% confidence intervals (CIs) were generated to compare piperaquine pharmacokinetic parameters between these two treatment periods. Compared with efavirenz-based ART, coadministration of dihydroartemisinin-piperaquine and dolutegravir-based ART resulted in a 57% higher overall piperaquine exposure (area under the concentration-time curve from 0 to 672 h [AUC0–672 h]) (GMR, 1.57; 90% CI, 1.28 to 1.93). Piperaquine’s day 7 concentrations were also 63% higher (GMR, 1.63; 90% CI, 1.29 to 2.11), while day 28 concentrations were nearly three times higher (GMR, 2.96; 90% CI, 2.25 to 4.07). However, the maximum piperaquine concentration (Cmax) remained similar (GMR, 1.09; 90% CI, 0.79 to 1.49). Dihydroartemisinin-piperaquine was well tolerated, with no medication-related serious adverse events observed in this small study. Compared with efavirenz-based ART, a known inducer of piperaquine metabolism, dolutegravir-based ART resulted in increased overall piperaquine exposure with pharmacokinetic parameter values that were similar to those published previously for pregnant and nonpregnant women. Our findings suggest that the efficacy of dihydroartemisinin-piperaquine will be retained in pregnant women on dolutegravir. (The study was registered on PACTR.samrc.ac.za [PACTR201910580840196].)

Published
2022

9. Dolutegravir drug-drug interactions

Author

Mondleki, E and Maartens, G

Abstract

Dolutegravir is neither an inducer nor an inhibitor of metabolising enzymes, and it therefore has a low propensity to act as a perpetrator of drug-drug interactions. Clinically significant decreases in dolutegravir exposure occur when it is co-administered with strong inducers (e.g. rifampicin, efavirenz) of drug metabolising enzymes and drug efflux transporters for which dolutegravir is a substrate – this can be overcome by increasing the dose of dolutegravir from 50 mg once daily to 50 mg twice daily. Dolutegravir significantly increases metformin plasma exposure: one must not exceed metformin 500 mg twice daily with concomitant dolutegravir. Divalent or trivalent cations chelate dolutegravir. Therefore, concomitant administration of dolutegravir with aluminium- and calcium-containing antacids should be avoided. Dolutegravir can be administered with calcium and iron supplements, provided these are taken together with food.

Published
2022

10. Optimized Loading Dose Strategies for Bedaquiline When Restarting Interrupted Drug-Resistant Tuberculosis Treatment

Author

Koele, S.E., Beek, S.W. van, Maartens, G., Brust, J.C.M., Svensson, E.M., Koele, S.E., Beek, S.W. van, Maartens, G., Brust, J.C.M., and Svensson, E.M.

Abstract

Item does not contain fulltext, Interruption of treatment is common in drug-resistant tuberculosis patients. Bedaquiline has a long terminal half-life; therefore, restarting after an interruption without a loading dose could increase the risk of suboptimal treatment outcome and resistance development. We aimed to identify the most suitable loading dose strategies for bedaquiline restart after an interruption. A model-based simulation study was performed. Pharmacokinetic profiles of bedaquiline and its metabolite M2 (associated with QT prolongation) were simulated for 5,000 virtual patients for different durations and starting points of treatment interruption. Weekly bedaquiline area under the concentration-time curve (AUC) and M2 maximum concentration (C(max)) deviation before interruption and after reloading were assessed to evaluate the efficacy and safety, respectively, of the reloading strategies. Bedaquiline weekly AUC and M2 C(max) deviation were mainly driven by the duration of interruption and only marginally by the starting point of interruption. For interruptions with a duration shorter than 2 weeks, no new loading dose is needed. For interruptions with durations between 2 weeks and 1 month, 1 month and 1 year, and longer than 1 year, reloading periods of 3 days, 1 week, and 2 weeks, respectively, are recommended. This reloading strategy results in an average bedaquiline AUC deviation of 1.88% to 5.98% compared with -16.4% to -59.8% without reloading for interruptions of 2 weeks and 1 year, respectively, without increasing M2 C(max). This study presents easy-to-implement reloading strategies for restarting a patient on bedaquiline treatment after an interruption.

Published
2022

11. Assessing Prolongation of the Corrected QT Interval with Bedaquiline and Delamanid Coadministration to Predict the Cardiac Safety of Simplified Dosing Regimens

Author

Tanneau, L., Karlsson, M.O., Rosenkranz, S.L., Cramer, Y.S., Shenje, J., Upton, C.M., Morganroth, J., Diacon, A.H., Maartens, G., Dooley, Kelly E., Svensson, E.M., Tanneau, L., Karlsson, M.O., Rosenkranz, S.L., Cramer, Y.S., Shenje, J., Upton, C.M., Morganroth, J., Diacon, A.H., Maartens, G., Dooley, Kelly E., and Svensson, E.M.

Abstract

Contains fulltext : 283109.pdf (Publisher’s version ) (Open Access), Delamanid and bedaquiline are two drugs approved to treat drug-resistant tuberculosis, and each have been associated with corrected QT interval (QTc) prolongation. We aimed to investigate the relationships between the drugs' plasma concentrations and the prolongation of observed QT interval corrected using Fridericia's formula (QTcF) and to evaluate their combined effects on QTcF, using a model-based population approach. Furthermore, we predicted the safety profiles of once daily regimens. Data were obtained from a trial where participants were randomized 1:1:1 to receive delamanid, bedaquiline, or delamanid + bedaquiline. The effect on QTcF of delamanid and/or its metabolite (DM-6705) and the pharmacodynamic interactions under coadministration were explored based on a published model between bedaquiline's metabolite (M2) and QTcF. The metabolites of each drug were found to be responsible for the drug-related QTcF prolongation. The final drug-effect model included a competitive interaction between M2 and DM-6705 acting on the same cardiac receptor and thereby reducing each other's apparent potency, by 28% (95% confidence interval (CI), 22-40%) for M2 and 33% (95% CI, 24-54%) for DM-6705. The generated combined effect was not greater but close to "additivity" in the analyzed concentration range. Predictions with the final model suggested a similar QT prolonging potential with simplified, once-daily dosing regimens compared with the approved regimens, with a maximum median change from baseline QTcF increase of 20 milliseconds in both regimens. The concentrations-QTcF relationship of the combination of bedaquiline and delamanid was best described by a competitive binding model involving the two main metabolites. Model predictions demonstrated that QTcF prolongation with simplified once daily regimens would be comparable to currently used dosing regimens.

Published
2022

12. Pharmacogenetics of Between-Individual Variability in Plasma Clearance of Bedaquiline and Clofazimine in South Africa

Author

Haas, D.W., Abdelwahab, M.T., Beek, S.W. van, Baker, P., Maartens, G., Bradford, Y., Ritchie, M.D., Wasserman, S., Meintjes, G., Beeri, K., Gandhi, N.R., Svensson, E.M., Denti, P., Brust, J.C.M., Haas, D.W., Abdelwahab, M.T., Beek, S.W. van, Baker, P., Maartens, G., Bradford, Y., Ritchie, M.D., Wasserman, S., Meintjes, G., Beeri, K., Gandhi, N.R., Svensson, E.M., Denti, P., and Brust, J.C.M.

Abstract

Item does not contain fulltext, BACKGROUND: Plasma bedaquiline clearance is reportedly more rapid with African ancestry. Our objective was to determine whether genetic polymorphisms explained between-individual variability in plasma clearance of bedaquiline, its M2 metabolite, and clofazimine in a cohort of patients treated for drug-resistant tuberculosis in South Africa. METHODS: Plasma clearance was estimated with nonlinear mixed-effects modeling. Associations between pharmacogenetic polymorphisms, genome-wide polymorphisms, and variability in clearance were examined using linear regression models. RESULTS: Of 195 cohort participants, 140 were evaluable for genetic associations. Among 21 polymorphisms selected based on prior genome-wide significant associations with any drug, rs776746 (CYP3A5∗3) was associated with slower clearance of bedaquiline (P = .0017) but not M2 (P = .25). CYP3A5∗3 heterozygosity and homozygosity were associated with 15% and 30% slower bedaquiline clearance, respectively. The lowest P value for clofazimine clearance was with VKORC1 rs9923231 (P = .13). In genome-wide analyses, the lowest P values for clearance of bedaquiline and clofazimine were with RFX4 rs76345012 (P = 6.4 × 10-7) and CNTN5 rs75285763 (P = 2.9 × 10-8), respectively. CONCLUSIONS: Among South Africans treated for drug-resistant tuberculosis, CYP3A5∗3 was associated with slower bedaquiline clearance. Different CYP3A5∗3 frequencies among populations may help explain the more rapid bedaquiline clearance reported in Africans. Associations with RFX4 and CNTN5 are likely by chance alone.

Published
2022

13. Population Pharmacokinetics of Delamanid and its Main Metabolite DM-6705 in Drug-Resistant Tuberculosis Patients Receiving Delamanid Alone or Coadministered with Bedaquiline

Author

Tanneau, L., Karlsson, M.O., Diacon, A.H., Shenje, J., Rios, J. De Los, Wiesner, L., Upton, C.M., Dooley, Kelly E., Maartens, G., Svensson, E.M., Tanneau, L., Karlsson, M.O., Diacon, A.H., Shenje, J., Rios, J. De Los, Wiesner, L., Upton, C.M., Dooley, Kelly E., Maartens, G., and Svensson, E.M.

Abstract

Item does not contain fulltext, BACKGROUND AND OBJECTIVE: Delamanid is a nitroimidazole, a novel class of drug for treating tuberculosis, and is primarily metabolized by albumin into the metabolite DM-6705. The aims of this analysis were to develop a population pharmacokinetic (PK) model to characterize the concentration-time course of delamanid and DM-6705 in adults with drug-resistant tuberculosis and to explore a potential drug-drug interaction with bedaquiline when coadministered. METHODS: Delamanid and DM-6705 concentrations after oral administration, from 52 participants (of whom 26 took bedaquiline concurrently and 20 were HIV-1 positive) enrolled in the DELIBERATE trial were analyzed using nonlinear mixed-effects modeling. RESULTS: Delamanid PK were described by a one-compartment disposition model with transit compartment absorption (mean absorption time of 1.45 h [95% confidence interval 0.501-2.20]) and linear elimination, while the PK of DM-6705 metabolite were described by a one-compartment disposition model with delamanid clearance as input and linear elimination. Predicted terminal half-life values for delamanid and DM-6705 were 15.1 h and 7.8 days, respectively. The impact of plasma albumin concentrations on delamanid metabolism was not significant. Bedaquiline coadministration did not affect delamanid PK. Other than allometric scaling with body weight, no patients' demographics were significant (including HIV). CONCLUSIONS: This is the first joint PK model of delamanid and its DM-6705 metabolite. As such, it can be utilized in future exposure-response or exposure-safety analyses. Importantly, albumin concentrations, bedaquiline coadministration, and HIV co-infection (dolutegravir coadministration) did not have an effect on delamanid and DM-6705 PK.

Published
2022

14. Focused investigations to expedite cancer diagnosis among patients with lymphadenopathy in a tuberculosis- and HIV-endemic region.

Author

Antel, Katherine, Oosthuizen, Jenna, Brown, Karryn, Malherbe, Francois, Loebenberg, Perry, Seaton, Cylene, Baloyi, Siphiwe, Simba, Kudakwashe, Chetty, Dharshnee, Louw, Vernon J., Maartens, Gary, Verburgh, Estelle R., Malherbe, F, Loebenberg, P, Baloyi, S, Simba, K, Chetty, D, Louw, V J, Maartens, G, and Verburgh, E R

Published
2023
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15. Study protocol for a phase 2A trial of the safety and tolerability of increased dose rifampicin and adjunctive linezolid, with or without aspirin, for HIV-associated tuberculous meningitis [LASER-TBM]

Author

Davis, AG, Wasserman, S, Maxebengula, M, Stek, C, Bremer, M, Daroowala, R, Aziz, S, Goliath, R, Stegmann, S, Koekemoer, S, Jackson, A, Lai Sai, L, Kadernani, Y, Sihoyiya, T, Liang, CJ, Dodd, L, Denti, P, Crede, T, Naude, J, Szymanski, P, Vallie, Y, Banderker, I, Moosa, S, Raubenheimer, P, Lai, RPJ, Joska, J, Nightingale, S, Dreyer, A, Wahl, G, Offiah, C, Vorster, I, Candy, S, Robertson, F, Meintjes, E, Maartens, G, Black, J, Meintjes, G, and Wilkinson, RJ

Abstract

Background: Tuberculous meningitis (TBM) is the most lethal form of tuberculosis with a mortality of ~50% in those co-infected with HIV-1. Current antibiotic regimens are based on those known to be effective in pulmonary TB and do not account for the differing ability of the drugs to penetrate the central nervous system (CNS). The host immune response drives pathology in TBM, yet effective host-directed therapies are scarce. There is sufficient data to suggest that higher doses of rifampicin (RIF), additional linezolid (LZD) and adjunctive aspirin (ASA) will be beneficial in TBM yet rigorous investigation of the safety of these interventions in the context of HIV associated TBM is required. We hypothesise that increased dose RIF, LZD and ASA used in combination and in addition to standard of care for the first 56 days of treatment with be safe and tolerated in HIV-1 infected people with TBM. Methods: In an open-label randomised parallel study, up to 100 participants will receive either; i) standard of care (n=40, control arm), ii) standard of care plus increased dose RIF (35mg/kg) and LZD (1200mg OD for 28 days, 600mg OD for 28 days) (n=30, experimental arm 1), or iii) as per experimental arm 1 plus additional ASA 1000mg OD (n=30, experimental arm 2). After 56 days participants will continue standard treatment as per national guidelines. The primary endpoint is death and the occurrence of solicited treatment-related adverse events at 56 days. In a planned pharmacokinetic (PK) sub-study we aim to assess PK/pharmacodynamic (PD) of oral vs IV rifampicin, describe LZD and RIF PK and cerebrospinal fluid concentrations, explore PK/PD relationships, and investigate drug-drug interactions between LZD and RIF. Safety and pharmacokinetic data from this study will inform a planned phase III study of intensified therapy in TBM. Clinicaltrials.gov registration: NCT03927313 (25/04/2019)

Published
2021

17. Disparities in Dolutegravir Uptake Affecting Females of Reproductive Age With HIV in Low- and Middle-Income Countries After Initial Concerns About Teratogenicity : An Observational Study

Author

Romo, M.L., Patel, R.C., Edwards, J.K., Humphrey, J.M., Musick, B.S., Bernard, C., Maina, M.W., Brazier, E., Castelnuovo, B., Penner, J., Wyka, K., Cardoso, S.W., Ly, P.S., Kunzekwenyika, C., Cortés, C.P., Panczak, R., Kelvin, E.A., Wools-Kaloustian, K.K., Nash, D., Khol, V., Zhang, F.J., Zhao, H.X., Han, N., Lee, M.P., Li, P.C.K., Lam, W., Wong, H.Y., Kumarasamy, N., Ezhilarasi, C., Pujari, S., Joshi, K., Gaikwad, S., Chitalikar, A., Merati, T.P., Wirawan, D.N., Yuliana, F., Yunihastuti, E., Imran, D., Widhani, A., Tanuma, J., Oka, S., Nishijima, T., Choi, J.Y., Na, S., Kim, J.M., Gani, Y.M., Rudi, N.B., Azwa, I., Kamarulzaman, A., Syed Omar, S.F., Ponnampalavanar, S., Ditangco, R., Pasayan, M.K., Mationg, M.L., Chan, Y.J., Ku, W.W., Ke, E., Wu, P.C., Ng, O.T., Lim, P.L., Lee, L.S., Yap, J.K., Avihingsanon, A., Gatechompol, S., Phanuphak, P., Phadungphon, C., Kiertiburanakul, S., Phuphuakrat, A., Chumla, L., Sanmeema, N., Chaiwarith, R., Sirisanthana, T., Praparattanapan, J., Nuket, K., Khuwuwan, S., Kantipong, P., Kambua, P., Nguyen, K.V., Bui, H.V., Nguyen, D.T.H., Nguyen, D.T., Do, C.D., Ngo, A.V., Nguyen, L.T., Sohn, A.H., Ross, J.L., Petersen, B., Law, M.G., Jiamsakul, A., Bijker, R., Rupasinghe, D., 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., Pinto, J., Ferreira, F., Maia, M., de Menezes Succi, R.C., Machado, D.M., de Fátima Barbosa Gouvêa, A., Wolff, M., Rodriguez, M.F., Allendes, G., Pape, J.W., Rouzier, V., Marcelin, A., Perodin, C., Luque, M.T., Padgett, D., Madero, J.S., Ramirez, B.C., Belaunzaran, P., Vega, Y.C., Gotuzzo Herencia, José Eduardo, Mejía Cordero, Fernando Alonso, Carriquiry, G., McGowan, C.C., Shepherd, B.E., Sterling, T., Jayathilake, K., Person, A.K., Rebeiro, P.F., Castilho, J., Duda, S.N., Maruri, F., Vansell, H., Jenkins, C., Kim, A., Lotspeich, S., Pélagie, N., Gateretse, P., Munezero, J., Nitereka, V., Niyongabo, T., Twizere, C., Bukuru, H., Nahimana, T., Baransaka, E., Barasukana, P., Kabanda, E., Manirakiza, M., Ndikumwenayo, F., Biziragusenyuka, J., Munezero, A.M.M., Nforniwe, D.N., Ajeh, R., Ngamani, M.L., Dzudie, A., Mbuh, A., Amadou, D., Yone, E.W.P., Kendowo, E., Akele, C., Clever, A., Kitetele, F., Lelo, P., Tabala, M., Ekembe, C., Kaba, D., Diafouka, M., Ekat, M.H., Nsonde, D.M., Mafoua, A., Christ, M.N., Igirimbabazi, J., Ayinkamiye, N., Uwineza, P., Ndamijimana, E., Habarurema, E., Nyiraneza, M.L., Nyiransabimana, M.L., Tuyisenge, L., Shyaka, C., Kankindi, C., Uwakijijwe, B., Ingabire, M.G., Ndumuhire, J., Nyirabahutu, M.G., Muyango, F., Bihibindi, J.C., Uwamahoro, O., Ndoli, Y., Nsanzimana, S., Mugwaneza, P., Remera, E., Umumararungu, E., Rwibasira, G.N., Habimana, D.S., Gasana, J., Kanyabwisha, F., Kubwimana, G., Muhoza, B., Munyaneza, A., Murenzi, G., Musabyimana, F., Umwiza, F., Ingabire, C., Tuyisenge, P., Butera, A.M., Kabahizi, J., Rurangwa, E., Feza, R., Mukashyaka, E., Benekigeri, C., Musaninyange, J., Adedimeji, A., Anastos, K., Dilorenzo, M., Murchison, L., Ross, J., Yotebieng, M., Addison, D., Jones, H., Kulkarni, S., Tymejczyk, O., Elul, B., Cai, X., Dong, A., Hoover, D., Kim, H.-Y., Li, C., Shi, Q., Lancaster, K., Kuniholm, M., Edmonds, A., Parcesepe, A., Edwards, J., Keiser, O., Kimmel, A., Diero, L., Ayaya, S., Sang, E., Bukusi, E., Mulwa, E., Nyanaro, G., Kasozi, C., Ssemakadde, M., Bwana, M.B., Muyindike, W., Byakwaga, H., Kanyesigye, M., Semeere, A., Matovu, J.M., Nalugoda, F., Wasswa, F.X., Kazyoba, P., Mayige, M., Lyamuya, R.E., Mayanga, F., Ngonyani, K., Lwali, J., Urassa, M., Nyaga, C., Machemba, R., Yiannoutsos, C., Vreeman, R., Syvertsen, J., Kantor, R., Martin, J., Wenger, M., Cohen, C., Kulzer, J., Maartens, G., Bolton, C., Wood, R., Sipambo, N., Tanser, F., Boulle, A., Fatti, G., Mbewe, S., Singh, E., Chimbetete, C., Technau, K., Eley, B., Muhairwe, J., Rafael, I., Fox, M.P., Prozesky, H., Anderegg, N., Ballif, M., Ostinelli, C.H.D., Egger, M., Fenner, L., Haas, A., Hossmann, S., Rohner, E., Riou, J., Skrivankova, V., Smith, L., Taghavi, K., von Groote, P., Wandeler, G., Zaniewski, E., Zürcher, K., Anderson, K., Cornell, M., Davies, M.-A., Iyun, V., Johnson, L., Kassanjee, R., Kehoe, K., Kubjane, M., Maxwell, N., Nyakato, P., Patten, G., Tlali, M., Tsondai, P., de Waal, R., and International epidemiology Databases to Evaluate AIDS (IeDEA)

Subjects
Adult, medicine.medical_specialty, Prevention, policy, and public health, Adolescent, Pyridones, Reproductive age, HIV Infections, Choice Behavior, Article, Piperazines, chemistry.chemical_compound, Acquired immunodeficiency syndrome (AIDS), Pregnancy, Epidemiology, Oxazines, Internal Medicine, Medicine, Humans, Maternal Health Services, Cumulative incidence, HIV Integrase Inhibitors, 610 Medicine & health, Developing Countries, Health equity, business.industry, HIV, Contraceptives, General Medicine, Middle Aged, medicine.disease, Antiretroviral therapy, Regimen, Pharmaceutical Preparations, chemistry, Dolutegravir, Observational study, Female, Age groups, Safety, business, Heterocyclic Compounds, 3-Ring, 360 Social problems & social services, Demography, Cohort study
Abstract

BACKGROUND The transition to dolutegravir-containing antiretroviral therapy (ART) in low- and middle-income countries (LMICs) was complicated by an initial safety signal in May 2018 suggesting that exposure to dolutegravir at conception was possibly associated with infant neural tube defects. On the basis of additional evidence, in July 2019, the World Health Organization recommended dolutegravir for all adults and adolescents living with HIV. OBJECTIVE To describe dolutegravir uptake and disparities by sex and age group in LMICs. DESIGN Observational cohort study. SETTING 87 sites that began using dolutegravir in 11 LMICs in the Asia-Pacific; Caribbean, Central and South America network for HIV epidemiology (CCASAnet); and sub-Saharan African regions of the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. PATIENTS 134��672 patients aged 16 years or older who received HIV care from January 2017 through March 2020. MEASUREMENTS Sex, age group, and dolutegravir uptake (that is, newly initiating ART with dolutegravir or switching to dolutegravir from another regimen). RESULTS Differences in dolutegravir uptake among females of reproductive age (16 to 49 years) emerged after the safety signal. By the end of follow-up, the cumulative incidence of dolutegravir uptake among females 16 to 49 years old was 29.4% (95% CI, 29.0% to 29.7%) compared with 57.7% (CI, 57.2% to 58.3%) among males 16 to 49 years old. This disparity was greater in countries that began implementing dolutegravir before the safety signal and initially had highly restrictive policies versus countries with a later rollout. Dolutegravir uptake was similar among females and males aged 50 years or older. LIMITATION Follow-up was limited to 6 to 8 months after international guidelines recommended expanding access to dolutegravir. CONCLUSION Substantial disparities in dolutegravir uptake affecting females of reproductive age through early 2020 are documented. Although this disparity was anticipated because of country-level restrictions on access, the results highlight its extent and initial persistence. PRIMARY FUNDING SOURCE National Institutes of Health.

Published
2021
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18. Effect of Clofazimine Concentration on QT Prolongation in Patients Treated for Tuberculosis

Author

Abdelwahab, M.T., Court, R., Everitt, D., Diacon, A.H., Dawson, R., Svensson, E.M., Maartens, G., Denti, P., Abdelwahab, M.T., Court, R., Everitt, D., Diacon, A.H., Dawson, R., Svensson, E.M., Maartens, G., and Denti, P.

Abstract

Item does not contain fulltext, Clofazimine is classified as a WHO group B drug for the treatment of rifampin-resistant tuberculosis. QT prolongation, which is associated with fatal cardiac arrhythmias, is caused by several antitubercular drugs, including clofazimine, but there are no data quantifying the effect of clofazimine concentration on QT prolongation. Our objective was to describe the effect of clofazimine exposure on QT prolongation. Fifteen adults drug-susceptible tuberculosis patients received clofazimine monotherapy as 300 mg daily for 3 days, followed by 100 mg daily in one arm of a 2-week, multiarm early bactericidal activity trial in South Africa. Pretreatment Fridericia-corrected QT (QTcF) (105 patients, 524 electrocardiograms [ECGs]) and QTcFs from the clofazimine monotherapy arm matched with clofazimine plasma concentrations (199 ECGs) were interpreted with a nonlinear mixed-effects model. Clofazimine was associated with significant QT prolongation described by a maximum effect (E(max)) function. We predicted clofazimine exposures using 100-mg daily doses and 2 weeks of loading with 200 and 300 mg daily, respectively. The expected proportions of patients with QTcF change from baseline above 30 ms (ΔQTcF > 30) were 2.52%, 11.6%, and 23.0% for 100-, 200-, and 300-mg daily doses, respectively. At steady state, the expected proportion with ΔQTcF of >30 ms was 23.7% and with absolute QTcF of >450 ms was 3.42% for all simulated regimens. The use of loading doses of 200 and 300 mg is not predicted to expose patients to an increased risk of QT prolongation, compared with the current standard treatment, and is, therefore, an alternative option for more quickly achieving therapeutic concentrations.

Published
2021

19. Relationship between Plasma and Intracellular Concentrations of Bedaquiline and Its M2 Metabolite in South African Patients with Rifampin-Resistant Tuberculosis

Author

Ngwalero, P., Brust, J.C.M., Beek, S.W. van, Wasserman, S., Maartens, G., Meintjes, G., Joubert, A., Norman, J., Castel, S., Gandhi, N.R., Denti, P., McIlleron, H., Svensson, E.M., Wiesner, L., Ngwalero, P., Brust, J.C.M., Beek, S.W. van, Wasserman, S., Maartens, G., Meintjes, G., Joubert, A., Norman, J., Castel, S., Gandhi, N.R., Denti, P., McIlleron, H., Svensson, E.M., and Wiesner, L.

Abstract

Contains fulltext : 244688.pdf (Publisher’s version ) (Open Access), Bedaquiline is recommended for the treatment of all patients with rifampin-resistant tuberculosis (RR-TB). Bedaquiline accumulates within cells, but its intracellular pharmacokinetics have not been characterized, which may have implications for dose optimization. We developed a novel assay using high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) to measure the intracellular concentrations of bedaquiline and its primary metabolite M2 in patients with RR-TB in South Africa. Twenty-one participants were enrolled and underwent sparse sampling of plasma and peripheral blood mononuclear cells (PBMCs) at months 1, 2, and 6 of treatment and at 3 and 6 months after bedaquiline treatment completion. Intensive sampling was performed at month 2. We used noncompartmental analysis to describe plasma and intracellular exposures and a population pharmacokinetic model to explore the relationship between plasma and intracellular pharmacokinetics and the effects of key covariates. Bedaquiline concentrations from month 1 to month 6 of treatment ranged from 94.7 to 2,540 ng/ml in plasma and 16.2 to 5,478 ng/ml in PBMCs, and concentrations of M2 over the 6-month treatment period ranged from 34.3 to 496 ng/ml in plasma and 109.2 to 16,764 ng/ml in PBMCs. Plasma concentrations of bedaquiline were higher than those of M2, but intracellular concentrations of M2 were considerably higher than those of bedaquiline. In the pharmacokinetic modeling, we estimated a linear increase in the intracellular-plasma accumulation ratio for bedaquiline and M2, reaching maximum effect after 2 months of treatment. The typical intracellular-plasma ratios 1 and 2 months after start of treatment were 0.61 (95% confidence interval [CI]: 0.42 to 0.92) and 1.10 (95% CI: 0.74 to 1.63) for bedaquiline and 12.4 (95% CI: 8.8 to 17.8) and 22.2 (95% CI: 15.6 to 32.3) for M2. The intracellular-plasma ratios for both bedaquiline and M2 were decreased by 54% (95% CI: 24 to 72%) in HIV-positive patien

Published
2021

24. Iqbal Haroon Master

Author

Ndjeka, N, primary, Reuter, A, additional, Conradie, F, additional, Enwerem, M, additional, Ferreira, H, additional, Hughes, J, additional, Ismail, F, additional, Ismail, N, additional, Kock, Y, additional, Padanilam, X, additional, Romero, R, additional, Schaaf, H S, additional, Te Riele, J, additional, Variava, E, additional, Meintjes, G, additional, and Maartens, G, additional

Published
2021
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26. 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

27. Isoniazid Preventive Therapy Added to ART to Prevent TB: An Individual Participant Data Meta-Analysis

Author

Ross, J, Badje, A, Rangaka, M, Walker, AS, Shapiro, A, Thomas, K, Anglaret, X, Eholie, S, Gabillard, D, Boulle, A, Maartens, G, Wilkinson, RJ, Ford, N, Golub, J, Williams, B, Barnabas, R, and Wellcome Trust

Subjects
parasitic diseases, 11 Medical and Health Sciences
Abstract

Background: Isoniazid preventive therapy prevents active tuberculosis in people with HIV, but previous studies have found no evidence of benefit in people with HIV who had a negative tuberculin skin test, and a non-significant effect on mortality. We aimed to estimate the effect of isoniazid preventive therapy given with antiretroviral therapy (ART) for the prevention of tuberculosis and death among people with HIV across population subgroups. Methods: We searched PubMed, Embase, the Cochrane database, and conference abstracts from database inception to Jan 15, 2019, to identify potentially eligible randomised trials. Eligible studies were trials that enrolled HIV-positive adults (age ≥15 years) taking ART who were randomly assigned to either daily isoniazid preventive therapy plus ART or ART alone and followed up longitudinally for outcomes of incident tuberculosis and mortality. We approached all authors of included trials and requested individual participant data: coprimary outcomes were relative risk of incident tuberculosis and all-cause mortality. We did a single-stage meta-analysis of individual participant data using stratified Cox-proportional hazards models. We did prespecified subgroup analyses by sex, CD4 cell count, and evidence of immune sensitisation to tuberculosis (indicated by tuberculin skin test or interferon-γ release assays [IGRAs]). We also assessed the relative risk of liver injury in an additional prespecified analysis. This study is registered with PROSPERO, CRD42019121400. Findings: Of 838 records, we included three trials with data for 2611 participants and 8584·8 person-years of follow-up for the outcome of incident tuberculosis, and a subset of 2362 participants with 8631·6 person-years of follow-up for the coprimary outcome of all-cause mortality. Risk for tuberculosis was lower in participants given isoniazid preventive therapy and ART than participants given ART alone (hazard ratio [HR] 0·68, 95% CI 0·49–0·95, p=0·02). Risk of all-cause mortality was lower in participants given isoniazid preventive therapy and ART than participants given ART alone, but this difference was non-significant (HR 0·69, 95% CI 0·43–1·10, p=0·12). Participants with baseline CD4 counts of less than 500 cells per μL had increased risk of tuberculosis, but there was no significant difference in the benefit of isoniazid preventive therapy with ART by sex, baseline CD4 count, or results of tuberculin skin test or IGRAs. 65 (2·5%) of 2611 participants had raised alanine aminotransferase, but data were insufficient to calculate an HR. Interpretation: Isoniazid preventive therapy with ART prevents tuberculosis across demographic and HIV-specific and tuberculosis-specific subgroups, which supports efforts to further increase use of isoniazid preventive therapy with ART broadly among people living with HIV. Funding: National Institutes of Health and National Institute of Allergy and Infectious Diseases.

Published
2020

28. Clofazimine pharmacokinetics in patients with TB: dosing implications

Author

Abdelwahab, Mahmoud Tareq, Wasserman, Sean, Brust, James C.M., Gandhi, Neel R., Meintjes, Graeme, Everitt, Daniel, Svensson, E.M., Maartens, G., Denti, Paolo, Abdelwahab, Mahmoud Tareq, Wasserman, Sean, Brust, James C.M., Gandhi, Neel R., Meintjes, Graeme, Everitt, Daniel, Svensson, E.M., Maartens, G., and Denti, Paolo

Abstract

Contains fulltext : 227463.pdf (Publisher’s version ) (Open Access)

Published
2020

29. The treatment gap for mental disorders in adults enrolled in HIV treatment programmes in South Africa: a cohort study using linked electronic health records

Author

Ruffieux, Y., primary, Efthimiou, O., additional, Van den Heuvel, L. L., additional, Joska, J. A., additional, Cornell, M., additional, Seedat, S., additional, Mouton, J. P., additional, Prozesky, H., additional, Lund, C., additional, Maxwell, N., additional, Tlali, M., additional, Orrell, C., additional, Davies, M.-A., additional, Maartens, G., additional, and Haas, A. D., additional

Published
2021
Full Text
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31. Implementing novel regimens for drug-resistant TB in South Africa: what can the world learn?

Author

Ndjeka, N., primary, Hughes, J., additional, Reuter, A., additional, Conradie, F., additional, Enwerem, M., additional, Ferreira, H., additional, Ismail, N., additional, Kock, Y., additional, Master, I., additional, Meintjes, G., additional, Padanilam, X., additional, Romero, R., additional, Schaaf, H. S., additional, Riele, J. te, additional, and Maartens, G., additional

Published
2020
Full Text
View/download PDF

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. -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

34. Confirming model-predicted pharmacokinetic interactions between bedaquiline and lopinavir/ritonavir or nevirapine in patients with HIV and drug-resistant tuberculosis

Author

Brill, M.J., Svensson, E.M., Pandie, M., Maartens, G., and Karlsson, M.O.

Subjects
lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4]
Abstract

Contains fulltext : 169933.pdf (Publisher’s version ) (Open Access) Bedaquiline and its metabolite M2 are metabolised by CYP3A4. The antiretrovirals ritonavir-boosted lopinavir (LPV/r) and nevirapine inhibit and induce CYP3A4, respectively. Here we aimed to quantify nevirapine and LPV/r drug-drug interaction effects on bedaquiline and M2 in patients co-infected with HIV and multidrug-resistant tuberculosis (MDR-TB) using population pharmacokinetic (PK) analysis and compare these with model-based predictions from single-dose studies in subjects without TB. An observational PK study was performed in three groups of MDR-TB patients during bedaquiline maintenance dosing: HIV-seronegative patients (n = 17); and HIV-infected patients using antiretroviral therapy including nevirapine (n = 17) or LPV/r (n = 14). Bedaquiline and M2 samples were collected over 48 h post-dose. A previously developed PK model of MDR-TB patients was used as prior information to inform parameter estimation using NONMEM. The model was able to describe bedaquiline and M2 concentrations well, with estimates close to their priors and earlier model-based interaction effects from single-dose studies. Nevirapine changed bedaquiline clearance to 82% (95% CI 67-99%) and M2 clearance to 119% (92-156%) of their original values, indicating no clinically significant interaction. LPV/r substantially reduced bedaquiline clearance to 25% (17-35%) and M2 clearance to 59% (44-69%) of original values. This work confirms earlier model-based predictions of nevirapine and LPV/r interaction effects on bedaquiline and M2 clearance from subjects without TB in single-dose studies, in MDR-TB/HIV co-infected patients studied here. To normalise bedaquiline exposure in patients with concomitant LPV/r therapy, an adjusted bedaquiline dosing regimen is proposed for further study.

Published
2017

35. The Lancet Respiratory Medicine Commission: 2019 update: epidemiology, pathogenesis, transmission, diagnosis, and management of multidrug-resistant and incurable tuberculosis

Author

Dheda, K, Gumbo, T, Maartens, G, Dooley, KE, Murray, M, Furin, J, Nardell, EA, Warren, RM, and Lancet Respiratory Medicine drug-resistant tuberculosis Commissi

Abstract

The Lancet Respiratory Medicine Commission on drug-resistant tuberculosis was published in 2017, which comprehensively reviewed and provided recommendations on various aspects of the disease. Several key new developments regarding drug-resistant tuberculosis are outlined in this Commission Update. The WHO guidelines on treating drug-resistant tuberculosis were updated in 2019 with a reclassification of second line anti-tuberculosis drugs. An injection-free MDR tuberculosis treatment regimen is now recommended. Over the past 3 years, advances in treatment include the recognition of the safety and mortality benefit of bedaquiline, the finding that the 9-11 month injectable-based 'Bangladesh' regimen was non-inferior to longer regimens, and promising interim results of a novel 6 month 3-drug regimen (bedaquiline, pretomanid, and linezolid). Studies of explanted lungs from patients with drug-resistant tuberculosis have shown substantial drug-specific gradients across pulmonary cavities, suggesting that alternative dosing and drug delivery strategies are needed to reduce functional monotherapy at the site of disease. Several controversies are discussed including the optimal route of drug administration, optimal number of drugs constituting a regimen, selection of individual drugs for a regimen, duration of the regimen, and minimal desirable standards of antibiotic stewardship. Newer rapid nucleic acid amplification test platforms, including point-of-care systems that facilitate active case-finding, are discussed. The rapid diagnosis of resistance to other drugs, (notably fluoroquinolones), and detection of resistance by targeted or whole genome sequencing will probably change the diagnostic landscape in the near future.

Published
2019

45. Pharmacokinetic interaction between bedaquiline and clofazimine in patients with drug-resistant tuberculosis

Author

Maartens, G., Brill, M. J. E., Pandie, M., Svensson, E. M., Maartens, G., Brill, M. J. E., Pandie, M., and Svensson, E. M.

Abstract

BACKGROUND: Bedaquiline (BDQ) and clofazimine (CFZ) are both recommended for treating drug-resistant tuberculosis (DR-TB). As CFZ is an inhibitor of the cytochrome P450 isoenzyme 3A4 (CYP3A4) in vitro, and BDQ a substrate of CYP3A4, there is a potential for pharmacokinetic (PK) drug-drug interaction that may result in increased BDQ exposure when co-administered with CFZ, which could increase the toxicity of BDQ. METHODS : We assessed the effect of co-administered CFZ on BDQ bioavailability, or on clearance of BDQ and its N-monodesmethyl metabolite (M2), in patients with DR-TB using a population PK model developed from data of patients with DR-TB. This was a secondary analysis of a study designed to explore drug-drug interactions between BDQ and antiretrovirals. RESULTS : Of 46 participants, 30 were on concomitant CFZ when intensive PK sampling of BDQ was done. CFZ did not have a statistically significant effect on BDQ bioavailability (-9.1%, 90% CI - 22.8 to +7.1; P = 0.19) or on BDQ and M2 clearance (+12.2%, 90% CI -13.7 to +38; P = 0.32). CONCLUSION: We did not find a statistically significant PK drug-drug interaction between BDQ and CFZ, but cannot exclude a potentially clinically relevant interaction due to the wide confidence intervals of the estimated interaction effects.

Published
2018
Full Text
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46. Book Reviews

Author

Bornman, P.C., Muller, L.M.M., Driver-Jowitt, J.P., Sommers, De K., Sawnepoel, R, Spracklen, F.H.N., Potgieter, P.D., Maartens, G, Lee, N.C., Morrell, D.F., Goodman, H.T., Heyns, C.F., and de Villiers, J.C.

Abstract

Book Review 1Book Title: Gastroenterological procedures: Manual of Gastroenterologic ProceduresBook Author: D.A. Drossman (Ed,)3rd ed. Pp. xv + 288. illustrated. New York: Raven Press. 1992.Book Review 2Book Title: Safety in diagnostic ultrasound: Exposure Criteria for Medical Diagnostic Ultrasound: I. Criteria Based on Thennal MechanismsBook Author: NCRP Report No. 113Pp. xv + 278. Illustrated. Bethesda MD: NCRP. 1992.Book Review 3Book Title: Knee arthroplasty: Total Knee ArthroplastyBook Author: James A. Rand (Ed.)pp. xiv + 464. illustrated. New York: Raven Press. 1992.Book Review 4Book Title: Drug-induced skin changes: Cutaneous Drug Reactions. An Integral Synopsis of Today's Systemic DrugsBook Authors: K. Zürcher & A. Krebs (Eds.)2nd Ed. pp. viii +570. Basel: Karger. 1992Book Review 5Book Title: Rabies WHO Expert Couunittee on Rabies: 8th ReportBook Author: WHOTechnical Report Series No. 824. Pp. vii + 84. Geneva: WHO. 1992.Book Review 6Book Title: Entomology and malaria. Entomological Field Techniques for Malaria ControlBook Author: WHOpp. 77. Geneva: WHO. 1992.Book Review 7Book Title: Handbook of PCVC. Handbook of Percutaneous Central Venous CatheterisationBook Authors: M. Rosen, P. Lano & S. Nig (Eds.)2nd Ed. pp. viii + 249. illustrated. Kent: Harcourt Brace and Jovanovich. 1992Book Review 8Book Title: HIV/AIDS resource directory: Resource Directory for HIV and AIDSBook Authors: Stewart Harris & Geoffrey Taylor (Eds.)83 + iv. 1992.Book Review 9Book Title: Laparoscopic surgery: Atlas of Laparoscopic SurgeryBook Authors: E. J. Reddick, with W. B. Say & J. D. Corbitt (Eds.)Pp. ix + 116. illustrated. New York: Raven Press. 1992Book Review 10Book Title: Medical history. The illustrated History of MedicineBook Author: Jean-Charles SourniaPp. 585. Illustrated. London: Harold Starke. 1992. (Distributed by Medical Association of South Africa, Private Bag XI, Pinelands 7430).Book Review 11Book Title: Plants in Cardiology. Plants in Cardiology Book Author: A. HollmanPp. vii + 40. Illustrated. London: BMJ. 1992.Book Review 12Book Title: Fraud in medical research. Fraud and Misconduct in Medical ResearchBook Authors: Stephen Lock & Frank Wells (Eds.)Pp. xi + 202. London: BMJ. 1993.Book Review 13Book Title: Anaesthesiology in emergencies Bailliere's Clinical Anaesthesiology: Emergency Medicine and the AnaesthetistBook Authors: H.H. Delooz (Ed.)Pp. xi + 212. Illustrated.London: Bailliere Tindall. 1992.Book Review 14Book Title: BMJ literary extracts. Soundings from BMJ ColunmistsBook Author: Ruth Holland (Ed.)Pp. xi + 89. London: BMJ 1992.Book Review 15Book Title: Chest imaging. Atlas of Chest Imaging: Correlated Anatomy with MRI and CTBook Authors: Marvin Wagner & Thomas L. Lawson (Eds.)Pp. ix + 134. lllustrated. New York: Raven Press. 1992.Book Review 16Book Title: Knee Meniscus: Basic and Clinical FoundationsBook Authors: Van C. Mow, Steven P. Amoczky & Douglas W. Jackson (Eds.)Pp. xi + 190. Illustrated. New York: Raven Press. 1992Book Review 17Book Title: Cryptorchidism. Descent of the TestisBook Authors: John M. Hutson & Spencer W. BeasleyPp. 187. Price: Illustrated. London: Edward Arnold. 1992.Book Review 18Book Title: Radiosurgery: Baseline and TrendsBook Authors: L. SteinerPp. xiv + 302. Illustrated. New York: Raven Press. 1992.

Published
2017

50. Clinician compliance with laboratory monitoring and prescribing guidelines in HIV 1-infected patients receiving tenofovir

Author

de Waal, R, Cohen, K, Fox, M P, Stinson, K, Maartens, G, Boulle, A, and Davies, M-A

Subjects
immune system diseases, virus diseases
Abstract

Background. Tenofovir is part of the preferred first-line regimen for HIV-infected patients in South Africa (SA), but is associated with kidney toxicity. SA antiretroviral therapy (ART) guidelines recommend creatinine monitoring at baseline (ART start) and at 3, 6 and 12 months, and substituting tenofovir with zidovudine, stavudine or abacavir should creatinine clearance (CrCl) decrease to

Published
2016

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