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128 results on '"Rokx, C."'

1. Non-AIDS Events in Individuals With Spontaneous Control of HIV-1

Author

Groenendijk, Albert L., Vos, Wilhelm A. J. W., Dos Santos, J.C., Rokx, C., Ven, A.J.A.M. van der, and Verbon, A.

Subjects
Acquired Immunodeficiency Syndrome, All institutes and research themes of the Radboud University Medical Center, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], Infectious Diseases, SDG 3 - Good Health and Well-being, Cardiovascular Diseases, HIV Seropositivity, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], HIV-1, Humans, HIV Infections, Pharmacology (medical)
Abstract

BACKGROUND: Despite antiretroviral therapy (ART), people living with HIV (PLHIV) are at increased risk for non-AIDS-defining events (nADEs), including cardiovascular events, non-AIDS malignances, hepatic disease, and bacterial pneumonia. SETTING: This systematic review seeks to answer the question: are PLHIV who spontaneously control HIV-1 subject to an increased risk of various nADEs relative to noncontrolling PLHIV on ART and people without HIV? METHODS: Databases were searched on June 9, 2021 with a search syntax focused on the elements "HIV," "spontaneous control," and "clinical outcomes": Embase.com (includes Embase and Medline), Medline Ovid (includes PubMed), Cochrane library, Web of Science, and Google Scholar. Included were studies reporting non-AIDS events in spontaneous controllers. Excluded were case reports, conference papers, editorials, and reviews. RESULTS: Of 1134 identified records, 34 were assessed for full-text and 12 studies were included in the qualitative synthesis: 5 cohorts, 2 cross-sectional prevalence studies, 4 cross-sectional imaging studies, and one case series. Four of 5 cohort studies showed that spontaneous controllers have a similar risk to develop nADEs compared with PLHIV on suppressive ART, specifically cardiovascular events, non-AIDS malignancies, hepatic disease, and bacterial pneumonia. Cross-sectional imaging studies showed a higher presence of subclinical cardiovascular disease in spontaneous controllers, than in people without HIV. CONCLUSION: Individuals with spontaneous control of HIV-1 do not seem to be at a greater risk to develop different nADEs compared with PLHIV on suppressive ART. More data are needed, because the present conclusions are based on a limited number of studies that show large heterogeneity among them.

Published
2022

2. National medical specialty guidelines of HIV indicator conditions in Europe lack adequate HIV testing recommendations: a systematic guideline review

Author

Jordans, C, Vasylyev, M, Rae, C, Jakobsen, M, Vassilenko, A, Dauby, N, Grevsen, A, Jakobsen, S, Raahauge, A, Champenois, K, Papot, E, Malin, J, Boender, T, Behrens, G, Gruell, H, Neumann, A, Spinner, C, Valbert, F, Akinosoglou, K, Kostaki, E, Nozza, S, Giacomelli, A, Lapadula, G, Mazzitelli, M, Torti, C, Matulionyte, R, Matulyte, E, Van Welzen, B, Hensley, K, Thompson, M, Ankiersztejn-Bartczak, M, Skrzat-Klapaczyńska, A, Săndulescu, O, Streinu-Cercel, A, Miron, V, Pokrovskaya, A, Hachfeld, A, Dorokhina, A, Sukach, M, Lord, E, Sullivan, A, Rokx, C, Jordans CCE, Vasylyev M, Rae C, Jakobsen ML, Vassilenko A, Dauby N, Grevsen AL, Jakobsen SF, Raahauge A, Champenois K, Papot E, Malin JJ, Boender TS, Behrens GMN, Gruell H, Neumann A, Spinner CD, Valbert F, Akinosoglou K, Kostaki EG, Nozza S, Giacomelli A, Lapadula G, Mazzitelli M, Torti C, Matulionyte R, Matulyte E, Van Welzen BJ, Hensley KS, Thompson M, Ankiersztejn-Bartczak M, Skrzat-Klapaczyńska A, Săndulescu O, Streinu-Cercel A, Miron VD, Pokrovskaya A, Hachfeld A, Dorokhina A, Sukach M, Lord E, Sullivan AK, Rokx C, Jordans, C, Vasylyev, M, Rae, C, Jakobsen, M, Vassilenko, A, Dauby, N, Grevsen, A, Jakobsen, S, Raahauge, A, Champenois, K, Papot, E, Malin, J, Boender, T, Behrens, G, Gruell, H, Neumann, A, Spinner, C, Valbert, F, Akinosoglou, K, Kostaki, E, Nozza, S, Giacomelli, A, Lapadula, G, Mazzitelli, M, Torti, C, Matulionyte, R, Matulyte, E, Van Welzen, B, Hensley, K, Thompson, M, Ankiersztejn-Bartczak, M, Skrzat-Klapaczyńska, A, Săndulescu, O, Streinu-Cercel, A, Miron, V, Pokrovskaya, A, Hachfeld, A, Dorokhina, A, Sukach, M, Lord, E, Sullivan, A, Rokx, C, Jordans CCE, Vasylyev M, Rae C, Jakobsen ML, Vassilenko A, Dauby N, Grevsen AL, Jakobsen SF, Raahauge A, Champenois K, Papot E, Malin JJ, Boender TS, Behrens GMN, Gruell H, Neumann A, Spinner CD, Valbert F, Akinosoglou K, Kostaki EG, Nozza S, Giacomelli A, Lapadula G, Mazzitelli M, Torti C, Matulionyte R, Matulyte E, Van Welzen BJ, Hensley KS, Thompson M, Ankiersztejn-Bartczak M, Skrzat-Klapaczyńska A, Săndulescu O, Streinu-Cercel A, Miron VD, Pokrovskaya A, Hachfeld A, Dorokhina A, Sukach M, Lord E, Sullivan AK, and Rokx C

Abstract

Background: Adequate identification and testing of people at risk for HIV is fundamental for the HIV care continuum. A key strategy to improve timely testing is HIV indicator condition (IC) guided testing. Aim: To evaluate the uptake of HIV testing recommendations in HIV IC-specific guidelines in European countries. Methods: Between 2019 and 2021, European HIV experts reviewed guideline databases to identify all national guidelines of 62 HIV ICs. The proportion of HIV IC guidelines recommending HIV testing was reported, stratified by subgroup (HIV IC, country, eastern/western Europe, achievement of 90-90-90 goals and medical specialty). Results: Of 30 invited European countries, 15 participated. A total of 791 HIV IC guidelines were identified: median 47 (IQR: 38-68) per country. Association with HIV was reported in 69% (545/791) of the guidelines, and 46% (366/791) recommended HIV testing, while 42% (101/242) of the AIDS-defining conditions recommended HIV testing. HIV testing recommendations were observed more frequently in guidelines in eastern (53%) than western (42%) European countries and in countries yet to achieve the 90-90-90 goals (52%) compared to those that had (38%). The medical specialties internal medicine, neurology/neurosurgery, ophthalmology, pulmonology and gynaecology/obstetrics had an HIV testing recommendation uptake below the 46% average. None of the 62 HIV ICs, countries or medical specialties had 100% accurate testing recommendation coverage in all their available HIV IC guidelines. Conclusion: Fewer than half the HIV IC guidelines recommended HIV testing. This signals an insufficient adoption of this recommendation in non-HIV specialty guidelines across Europe.

Published
2022

3. The BAF complex inhibitor pyrimethamine reverses HIV-1 latency in people with HIV-1 on antiretroviral therapy.

Author

Prins, H.A., Crespo, R., Lungu, C., Rao, S., Li, L, Overmars, R.J., Papageorgiou, G., Mueller, Y.M., Stoszko, M., Hossain, T., Kan, T.W., Rijnders, B.J.A., Bax, H.I., Gorp, E.C. van, Nouwen, J.L., Vries-Sluijs, T.E.M.S. De, Schurink, C.A.M., Mendonça Melo, M. de, Nood, E. van, Colbers, A., Burger, D.M., Palstra, R.J., Kampen, J. J. A. van, Vijver, D.A. van de, Mesplède, T., Katsikis, P.D., Gruters, R.A., Koch, B.C.P., Verbon, A., Mahmoudi, T., Rokx, C., Prins, H.A., Crespo, R., Lungu, C., Rao, S., Li, L, Overmars, R.J., Papageorgiou, G., Mueller, Y.M., Stoszko, M., Hossain, T., Kan, T.W., Rijnders, B.J.A., Bax, H.I., Gorp, E.C. van, Nouwen, J.L., Vries-Sluijs, T.E.M.S. De, Schurink, C.A.M., Mendonça Melo, M. de, Nood, E. van, Colbers, A., Burger, D.M., Palstra, R.J., Kampen, J. J. A. van, Vijver, D.A. van de, Mesplède, T., Katsikis, P.D., Gruters, R.A., Koch, B.C.P., Verbon, A., Mahmoudi, T., and Rokx, C.

Abstract

Contains fulltext : 291084.pdf (Publisher’s version ) (Open Access), Reactivation of the latent HIV-1 reservoir is a first step toward triggering reservoir decay. Here, we investigated the impact of the BAF complex inhibitor pyrimethamine on the reservoir of people living with HIV-1 (PLWH). Twenty-eight PLWH on suppressive antiretroviral therapy were randomized (1:1:1:1 ratio) to receive pyrimethamine, valproic acid, both, or no intervention for 14 days. The primary end point was change in cell-associated unspliced (CA US) HIV-1 RNA at days 0 and 14. We observed a rapid, modest, and significant increase in (CA US) HIV-1 RNA in response to pyrimethamine exposure, which persisted throughout treatment and follow-up. Valproic acid treatment alone did not increase (CA US) HIV-1 RNA or augment the effect of pyrimethamine. Pyrimethamine treatment did not result in a reduction in the size of the inducible reservoir. These data demonstrate that the licensed drug pyrimethamine can be repurposed as a BAF complex inhibitor to reverse HIV-1 latency in vivo in PLWH, substantiating its potential advancement in clinical studies.

Published
2023

5. Exploring the Breastfeeding Desires and Decision-Making of Women Living with HIV in the Netherlands: Implications for Perinatal HIV Management in Developed Countries.

Author

Bukkems, V.E., Finkenflügel, R.N.N., Grintjes, K.J., Marneef, Manon, Haan, M.C.J. de, Mielitz, I., Hulzen, A. van, Rokx, C., Leeuwen, Elisabeth van, Nellen, J.F., Burger, D.M., Colbers, A., Bukkems, V.E., Finkenflügel, R.N.N., Grintjes, K.J., Marneef, Manon, Haan, M.C.J. de, Mielitz, I., Hulzen, A. van, Rokx, C., Leeuwen, Elisabeth van, Nellen, J.F., Burger, D.M., and Colbers, A.

Abstract

Contains fulltext : 293270.pdf (Publisher’s version ) (Open Access), Introduction: Guidelines in high-income countries recommend women living with human immunodeficiency virus (HIV) to formula feed their newborns, because the possibility of mother-to-child-transmission of HIV during breastfeeding cannot be ruled out. It is an ongoing debate if the possible transmission risk outweighs the medical, cultural, psychological, and social importance of breastfeeding in women stable on current first-line suppressive antiretroviral regimens. The study aim was to explore breastfeeding desires and decision-making of immigrant and nonimmigrant women living with HIV in the Netherlands. Method: A questionnaire was administered orally or online to 82 women living with HIV in the Netherlands. The breastfeeding desires of the participants were collected as categorical data, and breastfeeding decision-making and willingness to adhere to additional monitoring were collected on a 5-point Likert scale. Categorical data were presented as proportions, and Likert scale data were presented in Likert scale bar plots. Results: Seventy-one percent of the participants expressed a desire to breastfeed in the future. The most important factors influencing decision-making to breastfeed were the chance of transmission of HIV to the infant and the advice by the doctor or nurse practitioner. Of the participants, 42% expressed their interest in breastfeeding with a <1/100 transmission risk. More than half of the participants expressed their interest to breastfeed with additional monitoring. Conclusions: A substantial proportion of the women living with HIV in the Netherlands has a desire to breastfeed, of which the majority are willing to adhere to additional monitoring to do so.

Published
2023

6. Exposure and virologic outcomes of dolutegravir combined with ritonavir boosted darunavir in treatment-naive individuals enrolled in the Netherlands Cohort Study on Acute HIV infection (NOVA)

Author

Prins, H. A. B., Zino, L., Svensson, Elin M., Verbon, A., de Bree, G. J., Prins, J. M., Reiss, P., Burger, D. M., Rokx, C., Colbers, A., Team, NOVA Study, Prins, H. A. B., Zino, L., Svensson, Elin M., Verbon, A., de Bree, G. J., Prins, J. M., Reiss, P., Burger, D. M., Rokx, C., Colbers, A., and Team, NOVA Study

Abstract

To the authors' knowledge, there is currently no literature or guidance recommendation regard-ing whether the dose of dolutegravir (DTG) should be increased when co-administered with darunavir/ritonavir (DRV/r) in patients with acute human immunodeficiency virus infection (AHI). This study assessed the pharmacokinetics (PK) of twice-daily (BID) DTG and once-daily (QD) DRV/r, and com-pared this with DTG QD without DRV/r in patients with AHI. Forty-six participants initiated antiretro-viral therapy within < 24 h of enrolment: DTG 50 mg BID, DRV/r 80 0/10 0 mg QD, and two nucleoside reverse transcriptase inhibitors (NRTIs) for 4 weeks (Phase I); and DTG 50 mg QD with two NRTIs there-after (Phase II: reference). Total DTG trough concentration (Ctrough) and area under the concentration-time profile of 0-24 h (AUC0-24h) were predicted using a population PK model. DTG glucuronidation metabolic ratio (MR) and DTG free fraction were determined and compared per treatment phase using geometric mean ratio (GMR) and 90% confidence interval (CI). Participants had a predicted geometric mean steady-state DTG Ctrough of 2.83 [coefficient of variation (CV%) 30.3%] mg/L (Phase I) and 1.28 (CV% 52.4%) mg/L (Phase II), with GMR of 2.20 (90% CI 1.90-2.55). Total exposure during DTG BID increased but did not double [AUC0-24h GMR 1.65 (90% CI 1.50-1.81) h.mg/L]. DTG glucuronidation MR increased by approxi-mately 29% during Phase I. DTG Ctrough was above in-vivo EC90 (0.32 mg/L) during both phases, except in one participant during Phase I. At Week 8, 84% of participants had viral loads <= 40 copies/mL. The drug-drug interaction between DTG (BID) and DRV/r (QD) was due to induced glucuronidation, and is not clinically relevant in patients with AHI.(c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ )

Published
2023
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7. Outcomes of Bariatric Surgery in People With Human Immunodeficiency Virus: A Retrospective Analysis From the ATHENA Cohort.

Author

Zino, L., Wit, F., Rokx, C., Hollander, J.G. den, Valk, M. van der, Richel, O., Burger, D.M., Colbers, A., Zino, L., Wit, F., Rokx, C., Hollander, J.G. den, Valk, M. van der, Richel, O., Burger, D.M., and Colbers, A.

Abstract

Item does not contain fulltext, BACKGROUND: The implications of bariatric surgery (BS) on virologic and metabolic outcomes in people with human immunodeficiency virus (HIV; PWH) on antiretroviral therapy (ART) are unknown. METHODS: Here, we report a retrospective analysis up to 18 months post-BS in PWH from the AIDS Therapy evaluation in The Netherlands (ATHENA) cohort with data from all dutch HIV treating Centers. Primary end points were a confirmed virologic failure (2 consecutive HIV-RNA measurements >200 copies/mL) and the percentage of patients who achieved >20% total body weight loss up to 18 months post-BS. Switches from baseline ART and trough plasma concentrations of antiretrovirals were also reported post-BS. Metabolic parameters and medication usage were compared pre- and post-BS. RESULTS: Fifty-one patients were included. One case of confirmed virologic failure and 3 cases with viral blips were detected in this cohort up to 18 months post-BS. Eighty-five percent of patients achieved >20% total body weight loss at 18 months post-BS, with a mean difference from baseline (95% confidence interval) of -33.5% (-37.7% to -29.3%). Trough plasma concentrations of measured antiretroviral agents were all above minimum effective concentrations, except for 1 sample of darunavir. Lipid profiles, but not serum creatinine and blood pressure, improved significantly (P < .01) post-BS. Total medications and obesity-related comedications declined from 203 to 103 and from 62 to 25, respectively, at 18 months post-BS. CONCLUSIONS: BS was an effective intervention for weight loss and lipid control in PWH using ART in this cohort with no clear link to poor virologic outcomes.

Published
2023

8. External validation of the PAGE-B score for HCC risk prediction in people living with HIV/HBV coinfection

Author

Egger, M., Hoffmann, M., Rauch, A., van der Valk, M., Goorhuis, A., Prins, J. M., van Vugt, M., Wit, F. W.M.N., Cornelissen, M. T.E., Jonges, M., Wolthers, K. C., Zaaijer, H. L., Peters, E. J.G., van Agtmael, M. A., Autar, R. S., Laan, L. M., van den Berge, M., Baas, S., van Arkel, A., Pronk, M. J.H., Alers, W., Nobel, H., Berrevoets, M. A.H., Brouwer, A. E., Rokx, C., Anas, A. A., Bax, H. I., van Gorp, E. C.M., van Nood, E., Nouwen, J. L., Rijnders, B. J.A., Schurink, C. A.M., Slobbe, L., de Vries-Sluijs, T. E.M.S., Bassant, N., van Beek, J. E.A., Vriesde, M., van Zonneveld, L. M., de Groot, J., van Kampen, J. J.A., Koopmans, M. P.G., Rahamat-Langendoen, J. C., Douma, R. A., Schippers, E. F., Gelinck, L. B.S., Mollema, F., Nguyen, T., Groeneveld, P. H.P., Lammers, A. J.J., de Boer, M. G.J., Claas, E. C.J., Brouwer, C. J., Mulder, E., Smit, J. V., van Niekerk, T., Pontesilli, O., van Tienen, C., van Wolfswinkel, M. E., Schippers, J., Kampschreur, L. M., Wagenaar, J., de Regt, M., Schouten, W. E.M., Veenstra, J., Blaauw, H., Knapen, M., Kok, M., Albers, M., de Haan, M., McCall, M., Burger, D., Claassen, M., Hassing, R. J., Verhagen, D. W.M., van Wijk, M., Bakker, M., Postma, D. F., Schenk, H. M., Boonstra, A., de Jonge, H., Niesters, H. G.M., Bruns, A. H.W., Hensgens, M. P.M., Oosterheert, J. J., Verbon, A., Berends, H., Bezemer, D. O., Smit, C., Bergsma, D., Lelivelt, K. J., van de Sande, L., van den Akker, M., Bakker, Y., Bezemer-Goedhart, M., Koster, L. E., Lucas, E. G.A., Schoorl, M. J.C., Witte, E. C.M., Peters, L., Larsen, J. F., Fischer, A. H., Jensen, S. K., Nguyen, D., Garcia, M., Egger, M., Hoffmann, M., Rauch, A., van der Valk, M., Goorhuis, A., Prins, J. M., van Vugt, M., Wit, F. W.M.N., Cornelissen, M. T.E., Jonges, M., Wolthers, K. C., Zaaijer, H. L., Peters, E. J.G., van Agtmael, M. A., Autar, R. S., Laan, L. M., van den Berge, M., Baas, S., van Arkel, A., Pronk, M. J.H., Alers, W., Nobel, H., Berrevoets, M. A.H., Brouwer, A. E., Rokx, C., Anas, A. A., Bax, H. I., van Gorp, E. C.M., van Nood, E., Nouwen, J. L., Rijnders, B. J.A., Schurink, C. A.M., Slobbe, L., de Vries-Sluijs, T. E.M.S., Bassant, N., van Beek, J. E.A., Vriesde, M., van Zonneveld, L. M., de Groot, J., van Kampen, J. J.A., Koopmans, M. P.G., Rahamat-Langendoen, J. C., Douma, R. A., Schippers, E. F., Gelinck, L. B.S., Mollema, F., Nguyen, T., Groeneveld, P. H.P., Lammers, A. J.J., de Boer, M. G.J., Claas, E. C.J., Brouwer, C. J., Mulder, E., Smit, J. V., van Niekerk, T., Pontesilli, O., van Tienen, C., van Wolfswinkel, M. E., Schippers, J., Kampschreur, L. M., Wagenaar, J., de Regt, M., Schouten, W. E.M., Veenstra, J., Blaauw, H., Knapen, M., Kok, M., Albers, M., de Haan, M., McCall, M., Burger, D., Claassen, M., Hassing, R. J., Verhagen, D. W.M., van Wijk, M., Bakker, M., Postma, D. F., Schenk, H. M., Boonstra, A., de Jonge, H., Niesters, H. G.M., Bruns, A. H.W., Hensgens, M. P.M., Oosterheert, J. J., Verbon, A., Berends, H., Bezemer, D. O., Smit, C., Bergsma, D., Lelivelt, K. J., van de Sande, L., van den Akker, M., Bakker, Y., Bezemer-Goedhart, M., Koster, L. E., Lucas, E. G.A., Schoorl, M. J.C., Witte, E. C.M., Peters, L., Larsen, J. F., Fischer, A. H., Jensen, S. K., Nguyen, D., and Garcia, M.

Abstract

Background & Aims: HBV coinfection is common among people living with HIV (PLWH) and is the most important cause of hepatocellular carcinoma (HCC). While risk prediction tools for HCC have been validated in patients with HBV monoinfection, they have not been evaluated in PLWH. Thus, we performed an external validation of PAGE-B in people with HIV/HBV coinfection. Methods: We included data on PLWH from four European cohorts who were positive for HBsAg and did not have HCC before starting tenofovir. We estimated the predictive performance of PAGE-B for HCC occurrence over 15 years in patients receiving tenofovir-containing antiretroviral therapy. Model discrimination was assessed after multiple imputation using Cox regression with the prognostic index as a covariate, and by calculating Harrell's c-index. Calibration was assessed by comparing our cumulative incidence with the PAGE-B derivation study using Kaplan-Meier curves. Results: In total, 2,963 individuals with HIV/HBV coinfection on tenofovir-containing antiretroviral therapy were included. PAGE-B was <10 in 26.5%, 10–17 in 57.7%, and ≥18 in 15.7% of patients. Within a median follow-up of 9.6 years, HCC occurred in 68 individuals (2.58/1,000 patient-years, 95% CI 2.03–3.27). The regression slope of the prognostic index for developing HCC within 15 years was 0.93 (95% CI 0.61–1.25), and the pooled c-index was 0.77 (range 0.73–0.80), both indicating good model discrimination. The cumulative incidence of HCC was lower in our study compared to the derivation study. A PAGE-B cut-off of <10 had a negative predictive value of 99.4% for the development of HCC within 5 years. Restricting efforts to individuals with a PAGE-B of ≥10 would spare unnecessary HCC screening in 27% of individuals. Conclusions: For individuals with HIV/HBV coinfection, PAGE-B is a valid tool to determine the need for HCC screening. Impact and impl

Published
2023

9. Exposure and virologic outcomes of dolutegravir combined with ritonavir boosted darunavir in treatment-naïve individuals enrolled in the Netherlands Cohort Study on Acute HIV infection (NOVA)

Author

Prins, H. A.B., Zino, L., Svensson, E. M., Verbon, A., de Bree, G. J., Prins, J. M., Reiss, P., Burger, D. M., Rokx, C., Colbers, A., Prins, H. A.B., Zino, L., Svensson, E. M., Verbon, A., de Bree, G. J., Prins, J. M., Reiss, P., Burger, D. M., Rokx, C., and Colbers, A.

Abstract

To the authors’ knowledge, there is currently no literature or guidance recommendation regarding whether the dose of dolutegravir (DTG) should be increased when co-administered with darunavir/ritonavir (DRV/r) in patients with acute human immunodeficiency virus infection (AHI). This study assessed the pharmacokinetics (PK) of twice-daily (BID) DTG and once-daily (QD) DRV/r, and compared this with DTG QD without DRV/r in patients with AHI. Forty-six participants initiated antiretroviral therapy within <24 h of enrolment: DTG 50 mg BID, DRV/r 800/100 mg QD, and two nucleoside reverse transcriptase inhibitors (NRTIs) for 4 weeks (Phase I); and DTG 50 mg QD with two NRTIs thereafter (Phase II: reference). Total DTG trough concentration (Ctrough) and area under the concentration–time profile of 0–24 h (AUC0–24h) were predicted using a population PK model. DTG glucuronidation metabolic ratio (MR) and DTG free fraction were determined and compared per treatment phase using geometric mean ratio (GMR) and 90% confidence interval (CI). Participants had a predicted geometric mean steady-state DTG Ctrough of 2.83 [coefficient of variation (CV%) 30.3%] mg/L (Phase I) and 1.28 (CV% 52.4%) mg/L (Phase II), with GMR of 2.20 (90% CI 1.90–2.55). Total exposure during DTG BID increased but did not double [AUC0–24h GMR 1.65 (90% CI 1.50–1.81) h.mg/L]. DTG glucuronidation MR increased by approximately 29% during Phase I. DTG Ctrough was above in-vivo EC90 (0.32 mg/L) during both phases, except in one participant during Phase I. At Week 8, 84% of participants had viral loads ≤40 copies/mL. The drug–drug interaction between DTG (BID) and DRV/r (QD) was due to induced glucuronidation, and is not clinically relevant in patients with AHI.

Published
2023

10. Evaluation of HIV-1 reservoir size and broadly neutralizing antibody (bNAb) susceptibility in individuals who initiated ART during acute and chronic infection

Author

Moldt, B., Gunthard, H., Workowski, K., Little, S., Eron, J., Overton, E., Lehmann, C., Rokx, C., Kozal, M., Gandhi, R., Liu, H., Makadzange, T., Collins, S., Geleziunas, R., and Callebaut, C.

Subjects
Antiviral agents -- Patient outcomes, AIDS (Disease) -- Research, AIDS research, HIV infection -- Development and progression -- Care and treatment, Health
Abstract

Background: The persistence of the viral reservoir is the main barrier to curing HIV. Initiation of ART during primary HIV infection can limit the size and diversity of the viral [...]

Published
2021
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11. Outpatient convalescent plasma therapy for high-risk patients with early COVID-19. A randomized placebo-controlled trial

Author

Gharbharan, A., Jordans, C., Zwaginga, L., Papageorgiou, G., Geloven, N. van, Wijngaarden, P. van, Hollander, J. den, Karim, F., Leeuwen-Segarceanu, E. van, Soetekouw, R., Lammers, J., Postma, D., Kampschreur, L., Groeneveld, G., Swaneveld, F., Schoot, C.E. van der, Gotz, H., Haagmans, B., Koopmans, M., Bogers, S., Geurtsvankessel, C., Zwaginga, J.J., Rokx, C., Rijnders, B., CoV-Early study grp, Clinical Haematology, Internal Medicine, Medical Microbiology & Infectious Diseases, Epidemiology, Public Health, and Virology

Subjects
Microbiology (medical), Infectious Diseases, Convalescent plasma, SDG 3 - Good Health and Well-being, Outpatients, COVID-19, General Medicine, Therapy, Antibodies
Abstract

Objectives: The potential benefit of convalescent plasma (CP) therapy for coronavirus disease 2019 (COVID-19) is highest when administered early after symptom onset. Our objective was to determine the effectiveness of CP therapy in improving the disease course of COVID-19 among high-risk outpatients. Methods: A multicentre, double-blind randomized trial was conducted comparing 300 mL of CP with non-CP. Patients were >= 50 years, were symptomatic for 50 years was 80%. Patients had a median age of 60 years, symptoms for 5 days, and 207 of 416 patients received CP therapy. During the 28 day follow-up, 28 patients were hospitalized and two died. The OR for an improved disease severity score with CP was 0.86 (95% credible interval, 0.59-1.22). The OR was 0.58 (95% CI, 0.33-1.02) for patients with

Published
2022

12. Lupus anticoagulant associates with thrombosis in patients with COVID-19 admitted to intensive care units

Author

Noordermeer, Tessa, Schutgens, Roger E. G., Visser, Chantal, Rademaker, Emma, de Maat, Moniek P. M., Jansen, A. J. Gerard, Limper, Maarten, Cremer, Olaf L., Kruip, Marieke J. H. A., Endeman, Henrik, Maas, Coen, de Laat, Bas, Urbanus, Rolf T., van de Beek, D., Brouwer, M. C., de Bruin, S., Coppens, M., van Es, N., van Haaps, T. F., Juffermans, N. P., Muller, M. C. A., Vlaar, A. P. J., Hertogh, C. M. P. M., Heunks, L. M. A., Hugtenburg, J. G., van Kooten, J., Nossent, E. J., Smulders, Y., Tuinman, P. R., Noordegraaf, A. Vonk, Grootenboers, M. J. J. H., van Guldener, C., Kant, M., Lansbergen, A., Faber, J., Hajer, G., Stemerdink, A., van den Akker, J., Bierings, R., Endeman, H., Goeijenbier, M., Hunfeld, N. G. M., van Gorp, E. C. M., Gommers, D. A. M. P. J., Koopmans, M. P. G., Kruip, M. J. H. A., Kuiken, T., Langerak, T., Leebeek, Lauw, M. N., de Maat, M. P. M., Noack, D., Paats, M. S., Raadsen, M. P., Rockx, B., Rokx, C., Schurink, C. A. M., Tong-Minh, K., van den Toorn, L., den Uil, C. A., Visser, C., Boutkourt, F., Roest, T., Douma, R. A., de Haan, L. R., ten Wolde, M., Bemelmans, R. H. H., Festen, B., Stads, S., de Jager, C. P. C., Simons, K. S., Antoni, M. L., Bos, M. H., Burggraaf, J. L. I., Cannegieter, S. C., Eikenboom, H. C. J., den Exter, P. L., Geelhoed, J. J. M., Huisman, M. V., de Jonge, E., Kaptein, F. H. J., Klok, F. A., Kroft, L. J. M., Lijfering, W. M., Nab, L., Ninaber, M. K., Putter, H., Ramai, S. R. S., da Rocha Rondon, A. M., Roukens, A. H. E., Stals, M. A. M., Versteeg, H. H., Vliegen, H. W., van Vlijmen, B. J. M., van de Berg, T., Bruggemann, R., van Bussel, B. C. T., ten Cate, H., ten Cate-Hoek, A., Hackeng, T. M., Henskens, ir. Y., Hulshof, A., Mulder, M., Olie, R. H., Schurgers, L., Spaetgens, B., Spronk, H., Spruit, M. A., Winckers, K., Nieuwenhuizen, L., Franken, B., Schrover, I. M., de Waal, E. G. M., Beishuizen, A., Cornet, A., Krabbe, J., Kramers, K., Leentjens, J., de Mast, Q., Middeldorp, S., Brouwer, R. E., Ellerbroek, J. L. J., Tijmensen, J., Hovens, M. M. C., Oostdijk, E. A. N., Westerhof, B. D., Faber, L. M., van den Biggelaar, M., Meijers, J. C. M., Voorberg, J., Kevenaar, M. E., Soei, Y. L., Wils, E. J., Croles, F. N., de Laat, B., Kamphuisen, P. W., Vink, R., Lisman, T., Meijer, K., van Tichelaar, Y. I. G., Cremer, O. L., Geersing, G., Kaasjager, H. A. H., Kusadasi, N., Huisman, A., Maas, C., Nijkeuter, M., Schutgens, R. E. G., Creveldkliniek, Van, Urbanus, R. T., Westerink, J., Faber, H. J., Koster, S. C. E., van Montfort, P., van Twist, D. J. L., RS: Carim - B01 Blood proteins & engineering, Biochemie, Hematology, Intensive Care, Neurology, ANS - Neuroinfection & -inflammation, Intensive Care Medicine, ACS - Pulmonary hypertension & thrombosis, AII - Inflammatory diseases, Vascular Medicine, ACS - Amsterdam Cardiovascular Sciences, Graduate School, ACS - Microcirculation, Medical Microbiology and Infection Prevention, ARD - Amsterdam Reproduction and Development, Experimental Vascular Medicine, Landsteiner Laboratory, ACS - Atherosclerosis & ischemic syndromes, Elderly care medicine, APH - Aging & Later Life, Clinical pharmacology and pharmacy, APH - Health Behaviors & Chronic Diseases, Pulmonary medicine, Internal medicine, ACS - Diabetes & metabolism, Intensive care medicine, General practice, and Amsterdam Gastroenterology Endocrinology Metabolism

Subjects
lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], lupus anticoagulant, risk factor, critically ill, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], COVID-19, Hematology, thrombosis, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18]
Abstract

Contains fulltext : 286889.pdf (Publisher’s version ) (Open Access) BACKGROUND: Thrombosis is a frequent and severe complication in patients with coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU). Lupus anticoagulant (LA) is a strong acquired risk factor for thrombosis in various diseases and is frequently observed in patients with COVID-19. Whether LA is associated with thrombosis in patients with severe COVID-19 is currently unclear. OBJECTIVE: To investigate if LA is associated with thrombosis in critically ill patients with COVID-19. PATIENTS/METHODS: The presence of LA and other antiphospholipid antibodies was assessed in patients with COVID-19 admitted to the ICU. LA was determined with dilute Russell's viper venom time (dRVVT) and LA-sensitive activated partial thromboplastin time (aPTT) reagents. RESULTS: Of 169 patients with COVID-19, 116 (69%) tested positive for at least one antiphospholipid antibody upon admission to the ICU. Forty (24%) patients tested positive for LA; of whom 29 (17%) tested positive with a dRVVT, 19 (11%) tested positive with an LA-sensitive aPTT, and 8 (5%) tested positive on both tests. Fifty-eight (34%) patients developed thrombosis after ICU admission. The odds ratio (OR) for thrombosis in patients with LA based on a dRVVT was 2.5 (95% confidence interval [CI], 1.1-5.7), which increased to 4.5 (95% CI, 1.4-14.3) in patients at or below the median age in this study (64 years). LA positivity based on a dRVVT or LA-sensitive aPTT was only associated with thrombosis in patients aged less than 65 years (OR, 3.8; 95% CI, 1.3-11.4) and disappeared after adjustment for C-reactive protein. CONCLUSION: Lupus anticoagulant on admission is strongly associated with thrombosis in critically ill patients with COVID-19, especially in patients aged less than 65 years.

Published
2022

14. A multinational Delphi consensus to end the COVID-19 public health threat

Author

Lazarus, J. V., Romero, D., Kopka, C. J., Karim, S. A., Abu-Raddad, L. J., Almeida, G., Baptista-Leite, R., Barocas, J. A., Barreto, M. L., Bar-Yam, Y., Bassat, Q., Batista, C., Bazilian, M., Chiou, S. -T., del Rio, C., Dore, G. J., Gao, G. F., Gostin, L. O., Hellard, M., Jimenez, J. L., Kang, G., Lee, N., Maticic, M., Mckee, M., Nsanzimana, S., Oliu-Barton, M., Pradelski, B., Pyzik, O., Rabin, K., Raina, S., Rashid, S. F., Rathe, M., Saenz, R., Singh, S., Trock-Hempler, M., Villapol, S., Yap, P., Binagwaho, A., Kamarulzaman, A., El-Mohandes, A., Barreto, M., Abdulla, S., Addleman, S., Aghayeva, G., Agius, R., Ahmed, M., Ramy, M. A., Aide, P., Aleman, S., Alfred, J. -P., Ali, S., Aliaga, J., Aloudat, T., Alqahtani, S. A., Al-Salman, J., Amuasi, J. H., Agrawal, A., Anwar, W., Araujo-Jorge, T., Artaza, O., Asadi, L., Awuku, Y., Baker, M., Barberia, L., Bascolo, E., Belcher, P., Bell, L., Benzaken, A., Bergholtz, E., Bhadelia, N., Bhan, A., Bilodeau, S., Bitran, R., Bluyssen, P., Bosman, A., Bozza, F. A., Brinkmann, M. M., Brown, A., Mellado, B., Bukusi, E., Bullen, C., Buonanno, G., Burgess, R., Butler, M., Byakika-Kibwika, P., Cabieses, B., Carlsson, G., Cascini, Fidelia, Chabala, C., Chakroun, M., Cheng, K. K., Chetty, A., Chumachenko, D., Consalves, G., Conway Morris, A., Cordie, A., Corrah, T., Crabtree-Ramirez, B., Dashdorj, N., Davidovitch, N., de Souza, L. E., Dhariwal, A. C., Druica, E., Ergonul, O., Erondu, N. A., Essar, M. Y., Ewing, A., Fanjul, G., Feierstein, D., Feigl-Ding, E., Figueroa, R., Figueroa, J. P., Fisher, D., Flores, W., Forero-Pena, D. A., Frumkin, H., Gamkrelidze, A., Gandhi, M., Garcia, P., Garcia-Basteiro, A. L., Garcia-Sastre, A., Garg, S., Gbeasor-Komlanvi, F. A., Gershenson, C., Gilada, I., Giovanella, L., Gonzalez, M., Green, M. S., Greenhalgh, T., Griffin, P., Griffin, S., Grinsztejn, B., Anand, T., Guerra, G., Guinto, R., Gujski, M., Guner, R., Hamdy, A., Hancean, M. -G., Haniffa, A., Hartigan-Go, K. Y., Hassan, H. K., Hay, S. I., Heino, M. T. J., Hel, Z., Hotez, P., Hu, J., Hukic, M., Ijsselmuiden, C., Iroko, D., Iskarous, M., Izugbara, C., Jacobs, C., Jadad, A. R., Jehan, F., Jordan, A., Jroundi, I., Kain, K., Kamberi, F., Karamov, E., Karan, A., Katz, R., Katzourakis, A., Kazembe, A., Khamis, F., Khamzayev, K., Khanyola, J., Khunti, K., Kiguli-Malwadde, E., Kim, W. J., Kirenga, B. J., Klimovsky, D., Kmush, B. L., Knaul, F., Kogevinas, M., Kristensen, F., Kumar, D., Kumar, R., Kvalsvig, A., Lacerda, M. V., Lal, A., Lawton, T., Lemery, J., Leonardi, A. J., Li, Y., Lottvall, J., Lounis, M., Maceira, D., Macintyre, C. R., Madani, A., Magiorkinis, G., Malekzadeh, R., Choisy, M., Marcelin, J. R., Marks, G. B., Marr, L., Marrazzo, J., Martina, A., Martin-Moreno, J. M., Mateos, C., Mayxay, M., Mazarati, J. B., Mboup, S., Mcdonald, J., Mcmillan, F., Mechili, E., Medici, A., Davis, S. L. M., Meier, P., Memish, Z. A., Menon, J., Menon, P., Mesiano-Crookston, J., Michie, S., Mikolasevic, I., Milicevic, O., Mishra, A. K., Mohamed, R., Mokdad, A. H., Monroy-Valle, M., Morawska, L., Moschos, S. A., Motawea, K., Mousavi, S. H., Mumtaz, G., Munene, P. K., Munoz Almagro, C., Muriuki, J., Muyingo, S., Naniche, D., Naylor, C. D., Ndembi, N., Nemec, J., Nesteruk, I., Ngaruiya, C., Nguyen, H., Nikolova, D., Nitzan, D., Norheim, O., Noushad, M., Ntoumi, F., Nyborg, G. A., Ochodo, E., Odabasi, Z., Okwen, M. P., Olivia, K., Ong, D. S. Y., Opara, I., Orozco, M., Oshitani, H., Pagel, C., Pai, M., Palsdottir, B., Papatheodoridis, G., Paraskevis, D., Leigh, J. P., Pecoul, B., Peichl, A., Perez-Then, E., Duc, P. P., Philippe, C., Pineda Rojas, A., Pladsen, C., Pozniak, A., Quiroga, R., Qureshi, H., Rampal, S., Ranney, M., Rathe, L., Ratzan, S., Raventos, H., Rees, H., Reis, R., Ricciardi, Walter, Rizk, N., Robalo, M., Robertson, E., Robinson, L., Rokx, C., Ros, T., Rottingen, J. -A., Rubin, M., Ruxrungtam, K., Sadirova, S., Saha, S., Salgado, N., Sanchez, L., Sangaramoorthy, T., Santamaria-Ulloa, C., Santos, R., Sawaf, B., Schneider, M. F., Schooley, R. T., Sener, A., Sepulveda, J., Shah, J., Shibani, M., Shoib, S., Sikazwe, I., Simaitis, A., Gill, A. S., Skhvitaridze, N., Sokolovic, M., Solomon, R., Solorzano, X., Springer, S. A., Srol, J., Staines, A., Stelfox, H. T., Strathdee, S., Sulaiman, L. H., Sutton, B., Svanaes, D., Swed, S., Sypsa, V., Sorensen, K., Tajudeen, R., Tan, A., Tang, J., Tanner, M., Sethi, T., Temmerman, M., Than, K. K., Tinto, H., Tometissi, S. P., Torres, I., Tshering, K. P., Tsiodras, S., Tsofa, B., Vahlne, A., Vargas, J. R., Bernal, I. D. V., Ventura, D., Vilasanjuan, R., Vipond, J., Wamala-Andersson, S., Wargocki, P., West, R., Weyand, A., White, T. M., Wolff, G., Yao, M., Yates, C. A., Yeboah, G., Yee-Sin, L., Yi, S., Teo, Y. -Y., Yong, P., Zamora-Mesia, V., Ovrehus, A., Cascini F. (ORCID:0000-0001-6499-0734), Ricciardi W. (ORCID:0000-0002-5655-688X), Lazarus, J. V., Romero, D., Kopka, C. J., Karim, S. A., Abu-Raddad, L. J., Almeida, G., Baptista-Leite, R., Barocas, J. A., Barreto, M. L., Bar-Yam, Y., Bassat, Q., Batista, C., Bazilian, M., Chiou, S. -T., del Rio, C., Dore, G. J., Gao, G. F., Gostin, L. O., Hellard, M., Jimenez, J. L., Kang, G., Lee, N., Maticic, M., Mckee, M., Nsanzimana, S., Oliu-Barton, M., Pradelski, B., Pyzik, O., Rabin, K., Raina, S., Rashid, S. F., Rathe, M., Saenz, R., Singh, S., Trock-Hempler, M., Villapol, S., Yap, P., Binagwaho, A., Kamarulzaman, A., El-Mohandes, A., Barreto, M., Abdulla, S., Addleman, S., Aghayeva, G., Agius, R., Ahmed, M., Ramy, M. A., Aide, P., Aleman, S., Alfred, J. -P., Ali, S., Aliaga, J., Aloudat, T., Alqahtani, S. A., Al-Salman, J., Amuasi, J. H., Agrawal, A., Anwar, W., Araujo-Jorge, T., Artaza, O., Asadi, L., Awuku, Y., Baker, M., Barberia, L., Bascolo, E., Belcher, P., Bell, L., Benzaken, A., Bergholtz, E., Bhadelia, N., Bhan, A., Bilodeau, S., Bitran, R., Bluyssen, P., Bosman, A., Bozza, F. A., Brinkmann, M. M., Brown, A., Mellado, B., Bukusi, E., Bullen, C., Buonanno, G., Burgess, R., Butler, M., Byakika-Kibwika, P., Cabieses, B., Carlsson, G., Cascini, Fidelia, Chabala, C., Chakroun, M., Cheng, K. K., Chetty, A., Chumachenko, D., Consalves, G., Conway Morris, A., Cordie, A., Corrah, T., Crabtree-Ramirez, B., Dashdorj, N., Davidovitch, N., de Souza, L. E., Dhariwal, A. C., Druica, E., Ergonul, O., Erondu, N. A., Essar, M. Y., Ewing, A., Fanjul, G., Feierstein, D., Feigl-Ding, E., Figueroa, R., Figueroa, J. P., Fisher, D., Flores, W., Forero-Pena, D. A., Frumkin, H., Gamkrelidze, A., Gandhi, M., Garcia, P., Garcia-Basteiro, A. L., Garcia-Sastre, A., Garg, S., Gbeasor-Komlanvi, F. A., Gershenson, C., Gilada, I., Giovanella, L., Gonzalez, M., Green, M. S., Greenhalgh, T., Griffin, P., Griffin, S., Grinsztejn, B., Anand, T., Guerra, G., Guinto, R., Gujski, M., Guner, R., Hamdy, A., Hancean, M. -G., Haniffa, A., Hartigan-Go, K. Y., Hassan, H. K., Hay, S. I., Heino, M. T. J., Hel, Z., Hotez, P., Hu, J., Hukic, M., Ijsselmuiden, C., Iroko, D., Iskarous, M., Izugbara, C., Jacobs, C., Jadad, A. R., Jehan, F., Jordan, A., Jroundi, I., Kain, K., Kamberi, F., Karamov, E., Karan, A., Katz, R., Katzourakis, A., Kazembe, A., Khamis, F., Khamzayev, K., Khanyola, J., Khunti, K., Kiguli-Malwadde, E., Kim, W. J., Kirenga, B. J., Klimovsky, D., Kmush, B. L., Knaul, F., Kogevinas, M., Kristensen, F., Kumar, D., Kumar, R., Kvalsvig, A., Lacerda, M. V., Lal, A., Lawton, T., Lemery, J., Leonardi, A. J., Li, Y., Lottvall, J., Lounis, M., Maceira, D., Macintyre, C. R., Madani, A., Magiorkinis, G., Malekzadeh, R., Choisy, M., Marcelin, J. R., Marks, G. B., Marr, L., Marrazzo, J., Martina, A., Martin-Moreno, J. M., Mateos, C., Mayxay, M., Mazarati, J. B., Mboup, S., Mcdonald, J., Mcmillan, F., Mechili, E., Medici, A., Davis, S. L. M., Meier, P., Memish, Z. A., Menon, J., Menon, P., Mesiano-Crookston, J., Michie, S., Mikolasevic, I., Milicevic, O., Mishra, A. K., Mohamed, R., Mokdad, A. H., Monroy-Valle, M., Morawska, L., Moschos, S. A., Motawea, K., Mousavi, S. H., Mumtaz, G., Munene, P. K., Munoz Almagro, C., Muriuki, J., Muyingo, S., Naniche, D., Naylor, C. D., Ndembi, N., Nemec, J., Nesteruk, I., Ngaruiya, C., Nguyen, H., Nikolova, D., Nitzan, D., Norheim, O., Noushad, M., Ntoumi, F., Nyborg, G. A., Ochodo, E., Odabasi, Z., Okwen, M. P., Olivia, K., Ong, D. S. Y., Opara, I., Orozco, M., Oshitani, H., Pagel, C., Pai, M., Palsdottir, B., Papatheodoridis, G., Paraskevis, D., Leigh, J. P., Pecoul, B., Peichl, A., Perez-Then, E., Duc, P. P., Philippe, C., Pineda Rojas, A., Pladsen, C., Pozniak, A., Quiroga, R., Qureshi, H., Rampal, S., Ranney, M., Rathe, L., Ratzan, S., Raventos, H., Rees, H., Reis, R., Ricciardi, Walter, Rizk, N., Robalo, M., Robertson, E., Robinson, L., Rokx, C., Ros, T., Rottingen, J. -A., Rubin, M., Ruxrungtam, K., Sadirova, S., Saha, S., Salgado, N., Sanchez, L., Sangaramoorthy, T., Santamaria-Ulloa, C., Santos, R., Sawaf, B., Schneider, M. F., Schooley, R. T., Sener, A., Sepulveda, J., Shah, J., Shibani, M., Shoib, S., Sikazwe, I., Simaitis, A., Gill, A. S., Skhvitaridze, N., Sokolovic, M., Solomon, R., Solorzano, X., Springer, S. A., Srol, J., Staines, A., Stelfox, H. T., Strathdee, S., Sulaiman, L. H., Sutton, B., Svanaes, D., Swed, S., Sypsa, V., Sorensen, K., Tajudeen, R., Tan, A., Tang, J., Tanner, M., Sethi, T., Temmerman, M., Than, K. K., Tinto, H., Tometissi, S. P., Torres, I., Tshering, K. P., Tsiodras, S., Tsofa, B., Vahlne, A., Vargas, J. R., Bernal, I. D. V., Ventura, D., Vilasanjuan, R., Vipond, J., Wamala-Andersson, S., Wargocki, P., West, R., Weyand, A., White, T. M., Wolff, G., Yao, M., Yates, C. A., Yeboah, G., Yee-Sin, L., Yi, S., Teo, Y. -Y., Yong, P., Zamora-Mesia, V., Ovrehus, A., Cascini F. (ORCID:0000-0001-6499-0734), and Ricciardi W. (ORCID:0000-0002-5655-688X)

Abstract

Despite notable scientific and medical advances, broader political, socioeconomic and behavioural factors continue to undercut the response to the COVID-19 pandemic1,2. Here we convened, as part of this Delphi study, a diverse, multidisciplinary panel of 386 academic, health, non-governmental organization, government and other experts in COVID-19 response from 112 countries and territories to recommend specific actions to end this persistent global threat to public health. The panel developed a set of 41 consensus statements and 57 recommendations to governments, health systems, industry and other key stakeholders across six domains: communication; health systems; vaccination; prevention; treatment and care; and inequities. In the wake of nearly three years of fragmented global and national responses, it is instructive to note that three of the highest-ranked recommendations call for the adoption of whole-of-society and whole-of-government approaches1, while maintaining proven prevention measures using a vaccines-plus approach2 that employs a range of public health and financial support measures to complement vaccination. Other recommendations with at least 99% combined agreement advise governments and other stakeholders to improve communication, rebuild public trust and engage communities3 in the management of pandemic responses. The findings of the study, which have been further endorsed by 184 organizations globally, include points of unanimous agreement, as well as six recommendations with >5% disagreement, that provide health and social policy actions to address inadequacies in the pandemic response and help to bring this public health threat to an end.

Published
2022

15. A highly virulent variant of HIV-1 circulating in the Netherlands

Author

Wymant, Chris, Bezemer, Daniela, Blanquart, François, Ferretti, Luca, Gall, Astrid, Hall, Matthew, Golubchik, Tanya, Bakker, Margreet, Ong, Swee Hoe, Zhao, Lele, Bonsall, David, de Cesare, Mariateresa, MacIntyre-Cockett, George, Abeler-Dörner, Lucie, Albert, Jan, Bannert, Norbert, Fellay, Jacques, Grabowski, M Kate, Gunsenheimer-Bartmeyer, Barbara, Günthard, Huldrych F, Kivelä, Pia, Kouyos, Roger D, Laeyendecker, Oliver, Meyer, Laurence, Porter, Kholoud, Ristola, Matti, van Sighem, Ard, Berkhout, Ben, Kellam, Paul, Cornelissen, Marion, Reiss, Peter, Fraser, Christophe, Aubert, V, Battegay, M, Bernasconi, E, Böni, J, Braun, D L, Bucher, H C, Burton-Jeangros, C, Calmy, A, Cavassini, M, Dollenmaier, G, Egger, M, Elzi, L, Fehr, J, Fellay, J, Furrer, H, Fux, C A, Gorgievski, M, Günthard, H, Haerry, D, Hasse, B, Hirsch, H H, Hoffmann, M, Hösli, I, Kahlert, C, Kaiser, L, Keiser, O, Klimkait, T, Kouyos, R, Kovari, H, Ledergerber, B, Martinetti, G, de Tejada, B Martinez, Marzolini, C, Metzner, K, Müller, N, Nadal, D, Nicca, D, Pantaleo, G, Rauch, A, Regenass, S, Rudin, C, Schöni-Affolter, F, Schmid, P, Speck, R, Stöckle, M, Tarr, P, Trkola, A, Vernazza, P, Weber, R, Yerly, S, van der Valk, M, Geerlings, S E, Goorhuis, A, Hovius, J W, Lempkes, B, Nellen, F J B, van der Poll, T, Prins, J M, Reiss, P, van Vugt, M, Wiersinga, W J, Wit, F W M N, van Duinen, M, van Eden, J, Hazenberg, A, van Hes, A M H, Pijnappel, F J J, Smalhout, S Y, Weijsenfeld, A M, Jurriaans, S, Back, N K T, Zaaijer, H L, Berkhout, B, Cornelissen, M T E, Schinkel, C J, Wolthers, K C, Peters, E J G, van Agtmael, M A, Autar, R S, Bomers, M, Sigaloff, K C E, Heitmuller, M, Laan, L M, Ang, C W, van Houdt, R, Jonges, M, Kuijpers, T W, Pajkrt, D, Scherpbier, H J, de Boer, C, van der Plas, A, van den Berge, M, Stegeman, A, Baas, S, Hage de Looff, L, Buiting, A, Reuwer, A, Veenemans, J, Wintermans, B, Pronk, M J H, Ammerlaan, H S M, van den Bersselaar, D N J, de Munnik, E S, Deiman, B, Jansz, A R, Scharnhorst, V, Tjhie, J, Wegdam, M C A, van Eeden, A, Nellen, J, Brokking, W, Elsenburg, L J M, Nobel, H, van Kasteren, M E E, Berrevoets, M A H, Brouwer, A E, Adams, A, van Erve, R, de Kruijf-van de Wiel, B A F M, Keelan-Phaf, S, van der Ven, B, Buiting, A G M, Murck, J L, de Vries-Sluijs, T E M S, Bax, H I, van Gorp, E C M, de Jong-Peltenburg, N C, de Mendonç A Melo, M, van Nood, E, Nouwen, J L, Rijnders, B J A, Rokx, C, Schurink, C A M, Slobbe, L, Verbon, A, Bassant, N, van Beek, J E A, Vriesde, M, van Zonneveld, L M, de Groot, J, Boucher, C A B, Koopmans, M P G, van Kampen, J J A, Fraaij, P L A, van Rossum, A M C, Vermont, C L, van der Knaap, L C, Visser, E, Branger, J, Douma, R A, Cents-Bosma, A S, Duijf-van de Ven, C J H M, Schippers, E F, van Nieuwkoop, C, van Ijperen, J M, Geilings, J, van der Hut, G, van Burgel, N D, Leyten, E M S, Gelinck, L B S, Mollema, F, Davids-Veldhuis, S, Tearno, C, Wildenbeest, G S, Heikens, E, Groeneveld, P H P, Bouwhuis, J W, Lammers, A J J, Kraan, S, van Hulzen, A 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Valette, Michel, Viget, Nathalie, Aissi, Emmanuelle, Biekre, Raphael, Cornavin, Pauline, Merrien, Dominique, Seghezzi, Jean-Christophe, Machado, Moise, Diab, Georges, Raffi, François, Bonnet, Bénédicte, Allavena, Clotilde, Grossi, Olivier, Reliquet, Véronique, Billaud, Eric, Brunet, Cecile, Bouchez, Sabelline, Morineau-Le Houssine, Pascale, Sauser, Fabienne, Boutoille, David, Besnier, Michel, Hue, Hervé, Hall, Nolwenn, Brosseau, Delphine, Souala, Faouzi, Michelet, Christian, Tattevin, Pierre, Arvieux, Cédric, Revest, Matthieu, Leroy, Helene, Chapplain, Jean-Marc, Dupont, Matthieu, Fily, Fabien, Patra-Delo, Solène, Lefeuvre, Céline, Bernard, Louis, Bastides, Frédéric, Nau, Pascale, Verdon, Renaud, de la Blanchardiere, Arnaud, Martin, Anne, Feret, Philippe, Geffray, Loïk, Daniel, Corinne, Rohan, Jennifer, Fialaire, Pascale, Chennebault, Jean Marie, Rabier, Valérie, Abgueguen, Pierre, Rehaiem, Sami, Luycx, Odile, Niault, Mathilde, Moreau, Philippe, Poinsignon, Yves, Goussef, Marie, Mouton-Rioux, Virginie, Houlbert, Dominique, Alvarez-Huve, Sandrine, Barbe, Frédérique, Haret, Sophie, Perre, Philippe, Leantez-Nainville, Sophie, Esnault, Jean-Luc, Guimard, Thomas, Suaud, Isabelle, Girard, Jean-Jacques, Simonet, Véronique, Debab, Yasmine, Schmit, Jean-Luc, Jacomet, Christine, Weinberck, Pierre, Genet, Claire, Pinet, Pauline, Ducroix, Sophie, Durox, Hélène, Denes, Éric, Abraham, Bruno, Gourdon, Florence, Antoniotti, Odile, Molina, Jean-Michel, Ferret, Samuel, Lascoux-Combe, Caroline, Lafaurie, Matthieu, Colin de Verdiere, Nathalie, Ponscarme, Diane, De Castro, Nathalie, Aslan, Alexandre, Rozenbaum, Willy, Pintado, Claire, Clavel, François, Taulera, Olivier, Gatey, Caroline, Munier, Anne-Lise, Gazaigne, Sandrine, Penot, Pauline, Conort, Guillaume, Lerolle, Nathalie, Leplatois, Anne, Balausine, Stéphanie, Delgado, Jeannine, Timsit, Julie, Tabet, Magda, Gerard, Laurence, Girard, Pierre-Marie, Picard, Odile, Tredup, Jürgen, Bollens, Diane, Valin, Nadia, Campa, Pauline, Bottero, Julie, Lefebvre, Benedicte, Tourneur, Muriel, Fonquernie, Laurent, Wemmert, Charlotte, Lagneau, Jean-Luc, Yazdanpanah, Yazdan, Phung, Bao, Pinto, Adriana, Vallois, Dorothée, Cabras, Ornella, Louni, Françoise, Pialoux, Gilles, Lyavanc, Thomas, Berrebi, Valérie, Chas, Julie, Lenagat, Sophie, Rami, Agathe, Diemer, Myriam, Parrinello, Maguy, Depond, Audrey, Salmon, Dominique, Guillevin, Loïc, Tahi, Tassadit, Belarbi, Linda, Loulergue, Pierre, Zak Dit Zbar, Olivier, Launay, Odile, Silbermann, Benjamin, Leport, Catherine, Alagna, Laura, Pietri, Marie-Pierre, Simon, Anne, Bonmarchand, Manuela, Amirat, Naouel, Pichon, François, Kirstetter, Myriam, Katlama, Christine, Valantin, Marc Antoine, Tubiana, Roland, Caby, Fabienne, Schneider, Luminita, Ktorza, Nadine, Calin, Ruxandra, Merlet, Audrey, Ben Abdallah, Saadia, Weiss, Laurence, Buisson, Martin, Batisse, Dominique, Karmochine, Marina, Pavie, Juliette, Minozzi, Catherine, Jayle, Didier, Castel, Philippe, Derouineau, Jean, Kousignan, Pascale, Eliazevitch, Murielle, Pierre, Isabelle, Collias, Lio, Viard, Jean-Paul, Gilquin, Jacques, Sobel, Alain, Slama, Laurence, Ghosn, Jade, Hadacek, Blanka, Thu-Huyn, Nugyen, Nait-Ighil, Lella, Cros, Agnes, Maignan, Aline, Duvivier, Claudine, Consigny, Paul Henri, Lanternier, Fanny, Shoai-Tehrani, Michka, Touam, Fatima, Jerbi, Saadia, Bodard, Loïc, Jung, Corinne, Goujard, Cécile, Quertainmont, Yann, Duracinsky, Martin, Segeral, Olivier, Blanc, Arnaud, Peretti, Delphine, Cheret, Antoine, Chantalat, Christelle, Dulucq, Marie Josée, Levy, Yves, Lelievre, Jean Daniel, Lascaux, Anne Sophie, Dumont, Cécile, Boue, François, Chambrin, Véronique, Abgrall, Sophie, Kansau, Imad, Raho-Moussa, Mariem, De Truchis, Pierre, Dinh, Aurélien, Davido, Benjamin, Marigot, Dhiba, Berthe, Huguette, Devidas, Alain, Chevojon, Pierre, Chabrol, Amélie, Agher, Nouara, Lemercier, Yvon, Chaix, Fabrice, Turpault, Isabelle, Bouchaud, Olivier, Honore, Patricia, Rouveix, Elisabeth, Reimann, Evelyne, Belan, Alix Greder, Godin Collet, Claire, Souak, Safia, Mortier, Emmanuel, Bloch, Martine, Simonpoli, Anne-Marie, Manceron, Véronique, Cahitte, Isabelle, Hiraux, Emmanuel, Lafon, Erik, Cordonnier, François, Zeng, Ai-Feng, Zucman, David, Majerholc, Catherine, Bornarel, Dominique, Uludag, Agnès, Gellen-Dautremer, Justine, Lefort, Agnès, Bazin, Christine, Daneluzzi, Vincent, Gerbe, Juliette, Jeantils, Vincent, Coupard, Mélissa, Patey, Olivier, Bantsimba, Jonas, Delllion, Sophie, Paz, Pauline Caraux, Cazenave, Benoit, Richier, Laurent, Garrait, Valérie, Delacroix, Isabelle, Elharrar, Brigitte, Vittecoq, Daniel, Bolliot, Claudine, Lepretre, Annie, Genet, Philippe, Masse, Virginie, Perrone, Véronique, Boussard, Jean-Luc, Chardon, Patricia, Froguel, Eric, Simon, Philippe, Tassi, Sylvie, Avettand Fenoel, Véronique, Barin, Francis, Bourgeois, Christine, Cardon, Fanny, Chaix, Marie-Laure, Delfraissy, Jean François, Essat, Asma, Fischer, Hugues, Lecuroux, Camille, Petrov-Sanchez, Ventzislava, Rouzioux, Christine, Saez-Cirion, Asier, Seng, Rémonie, Kuldanek, Kristin, Mullaney, Scott, Young, Carmel, Zucchetti, Antonella, Bevan, Margaret-Ann, McKernan, Sinead, Wandolo, Emily, Richardson, Celia, Youssef, Elaney, Green, Pippa, Faulkner, Sue, Faville, Rebecca, Herman, Sandra, Care, Christine, Blackman, Helen, Bellenger, Katharine, Fairbrother, Keith, Phillips, Andrew, Babiker, Abdel, Delpech, Valerie, Fidler, S, Clarke, Mindy, Fox, Julie, Gilson, R, Goldberg, David, Hawkins, David, Johnson, Anne, Johnson, Margaret, McLean, Ken, Nastouli, Eleni, Post, Frank, Kennedy, N, Pritchard, J, Andrady, U, Rajda, N, Donnelly, C, McKernan, S, Drake, S, Gilleran, G, White, D, Ross, J, Harding, J, Faville, R, Sweeney, J, Flegg, P, Toomer, S, Wilding, H, Woodward, R, Dean, G, Richardson, C, Perry, N, Gompels, M, Jennings, L, Bansaal, D, Browing, M, Connolly, L, Stanley, B, Estreich, S, Magdy, A, O'Mahony, C, Fraser, P, Jebakumar, S P R, David, L, Mette, R, Summerfield, H, Evans, M, White, C, Robertson, R, Lean, C, Morris, S, Winter, A, Faulkner, S, Goorney, B, Howard, L, Fairley, I, Stemp, C, Short, L, Gomez, M, Young, F, Roberts, M, Green, S, Sivakumar, K, Minton, J, Siminoni, A, Calderwood, J, Greenhough, D, DeSouza, C, Muthern, Lisa, Orkin, C, Murphy, S, Truvedi, M, McLean, K, Hawkins, D, Higgs, C, Moyes, A, Antonucci, S, McCormack, S, Lynn, W, Bevan, M, Fox, J, Teague, A, Anderson, J, Mguni, S, Post, F, Campbell, L, Mazhude, C, Russell, H, Carrick, G, Ainsworth, J, Waters, A, Byrne, P, Johnson, M, Kuldanek, K, Mullaney, S, Lawlor, V, Melville, R, Sukthankar, A, Thorpe, S, Murphy, C, Wilkins, E, Ahmad, S, Green, P, Tayal, S, Ong, E, Meaden, J, Riddell, L, Loay, D, Peacock, K, Blackman, H, Harindra, V, Saeed, A M, Allen, S, Natarajan, U, Williams, O, Lacey, H, Care, C, Bowman, C, Herman, S, Devendra, S V, Wither, J, Bridgwood, A, Singh, G, Bushby, S, Kellock, D, Young, S, Rooney, G, Snart, B, Currie, J, Fitzgerald, M, Arumainayyagam, J, Chandramani, S, Rajamanoharan, S, Robinson, T, Taylor, B, Brewer, C, Mayr, Christoph, Schmidt, Wolfgang, Speidel, Andrea, Strohbach, Frank, Arastéh, Keikawus, Cordes, Christiane, Stündel, Manfred, Claus, Jörg, Baumgarten, Axel, Carganico, Andreas, Ingiliz, Patrick, Dupke, Stephan, Freiwald, Matthias, Rausch, Michael, Moll, Arend, Schleehauf, Dorothea, Hintsche, Bettina, Klausen, Gerd, Jessen, Heiko, Jessen, Arne, Köppe, Siegfried, Kreckel, Peter, Schranz, Dietmar, Fischer, Klaus, Schulbin, Hubert, Speer, Miriam, Glaunsinger, Tobias, Wicke, Thomas, Bieniek, Bernhard, Hillenbrand, Heribert, Schlote, Frank, Lauenroth-Mai, Elke, Schuler, Christoph, Schürmann, Dirk, Wesselmann, Hans, Brockmeyer, Norbert, Gehring, Peter, Schmalöer, Dirk, Hower, Martin, Spornraft-Ragaller, Petra, Häussinger, Dieter, Reuter, Stefan, Esser, Stefan, Markus, Rudolf, Kreft, Burkhard, Berzow, Dirk, Christl, Andreas, Meyer, Andreas, Plettenberg, Andreas, Stoehr, Albrecht, Graefe, Katrin, Lorenzen, Thore, Adam, Axel, Schewe, Knut, Weitner, Lutwin, Fenske, Stefan, Hansen, Stefan, Stellbrink, Hans-Jürgen, Wiemer, Dorothea, Hertling, Sandra, Schmidt, Reinhold, Arbter, Peter, Claus, Bernd, Galle, Peter, Jäger, Hans, Jä Gel-Guedes, Eva, Postel, Nils, Fröschl, Monika, Spinner, Christoph, Bogner, Johannes, Salzberger, Bernd, Schölmerich, Jürgen, Audebert, Franz, Marquardt, Ties, Schaffert, Andreas, Schnaitmann, Eiko, Trein, Andreas, Frietsch, Bernhard, Müller, Marcus, Ulmer, Albrecht, Detering-Hübner, Barbara, Kern, Peter, Schubert, Franz, Dehn, Günther, Schreiber, Maria, Güler, Cengiz, Schmidt, Daniel, Meixenberger, Karolin, Medical Microbiology & Infectious Diseases, Internal Medicine, Virology, Pediatrics, Medical Microbiology and Infection Prevention, AII - Infectious diseases, Global Health, Infectious diseases, APH - Aging & Later Life, Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Internal medicine, VU University medical center, Surgery, AMS - Rehabilitation & Development, APH - Quality of Care, Psychiatry, Pediatric surgery, Neurology, Public and occupational health, APH - Mental Health, Pathology, Cardiology, ACS - Heart failure & arrhythmias, Anesthesiology, IOO, Rehabilitation medicine, Obstetrics and gynaecology, General practice, Gastroenterology and hepatology, Pulmonary medicine, ACS - Pulmonary hypertension & thrombosis, Medical oncology laboratory, Hematology, Epidemiology and Data Science, Physiology, Microbes in Health and Disease (MHD), University of Oxford, Stichting HIV Monitoring [Amsterdam], Universiteit van Amsterdam (UvA), European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, Amsterdam UMC - Amsterdam University Medical Center, The Wellcome Trust Sanger Institute [Cambridge], Karolinska Institutet [Stockholm], Robert Koch Institute [Berlin] (RKI), Ecole Polytechnique Fédérale de Lausanne (EPFL), Johns Hopkins University (JHU), Universität Zürich [Zürich] = University of Zurich (UZH), Helsinki University Hospital [Helsinki, Finlande], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), 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, University College of London [London] (UCL), Kymab Ltd, Cambridge, England, Institut Pasteur [Paris] (IP), This study was funded by ERC Advanced Grant PBDR-339251 and a Li Ka Shing Foundation grant, both awarded to C.F. The ATHENA Cohort is managed by Stichting HIV Monitoring and supported by a grant from the Dutch Ministry of Health, Welfare and Sport through the Centre for Infectious Disease Control of the National Institute for Public Health and the Environment., We thank K. Fransen and G. Vanham for help with the Belgian data, O. Ratmann for help in identifying the Dutch clusters, K. Kusejko for testing for additional VB individuals in the SHCS, B. Foley for help with genome sharing, B. Dearlove and L. Thomson for help with software, and J. Herbeck and three other reviewers for helpful suggestions., Contributors and affiliations are listed in the supplementary materials., Department of Medicine, University of Helsinki, Infektiosairauksien yksikkö, HUS Inflammation Center, and Clinicum

Subjects
Adult, Male, HIV-1/genetics, Genotype, Anti-HIV Agents, Evolution, [SDV]Life Sciences [q-bio], lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], HIV Infections/drug therapy, selection, HIV Infections, Genome, Viral, heritability, epidemic, human-immunodeficiency-virus, Evolution, Molecular, SDG 3 - Good Health and Well-being, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Humans, Viral, Phylogeny, Netherlands, Multidisciplinary, Genome, model, Virulence, transmission, Molecular, setpoint viral load, reverse-transcriptase, dynamics, Viral Load, CD4 Lymphocyte Count, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], 3121 General medicine, internal medicine and other clinical medicine, Anti-HIV Agents/therapeutic use, Mutation, HIV-1, Female, progression
Abstract

Comment in Does HIV-1 virulence matter in the ART era? Lewitus E, Rolland M. Med (N Y). 2022 Apr 8;3(4):217-219. doi: 10.1016/j.medj.2022.03.003. PMID: 35590149; International audience; We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log 10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV—CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences—is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence.

Published
2022

17. Launching a multidisciplinary European collaboration towards a cure for HIV: The EU2Cure Consortium

Author

Rokx, C., primary, Prins, H.A.B., additional, Vandekerckhove, L., additional, Fidler, S.J., additional, Frater, J., additional, Bracchi, M., additional, Søgaard, O.S., additional, Tolstrop, M., additional, Rasmussen, T.A., additional, Salgado, M., additional, Blanco, J., additional, Martinez-Picado, J., additional, Clotet, B., additional, Tambussi, G., additional, Groenendijk, A., additional, Verbon, A., additional, and Boucher, C.A.B., additional

Published
2021
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19. A European review of HIV testing recommendations in national specialty guidelines for the management of HIV indicator conditions

Author

Jordans, C. C., Rae, C., Jacobsen, M. L., Akinosoglou, K., Arends, J., Dauby, N., Hachfeld, A., Malin, J. J., Matulionyte, R., Nozza, S., Pokrovskaya, A., Sandulescu, O., Thompson, M., Vassilenko, A., Torti, C., Giacomelli, A., Lapadula, G., Mazzitelli, M., Behrens, G., Spinner, C., Gruell, H., Neumann, Anja, Kostaki, E. G., Ankiersztejn-Bartczak, M., Skrzat-Klapaczynska, A., Matulyte, E., Lord, E., Sullivan, A., Rokx, C., and Grp, Guidelines Europe Review

Subjects
Medizin
Published
2021

21. The dolutegravir/valproic acid drug-drug interaction is primarily based on protein displacement

Author

Bollen, P.D.J., Prins, H.A., Colbers, A., Velthoven-Graafland, K., Rijnders, B.J.A., Vries-Sluijs, T.E.M.S. De, Burger, D.M., Rokx, C., Bollen, P.D.J., Prins, H.A., Colbers, A., Velthoven-Graafland, K., Rijnders, B.J.A., Vries-Sluijs, T.E.M.S. De, Burger, D.M., and Rokx, C.

Abstract

Contains fulltext : 233990.pdf (Publisher’s version ) (Closed access)

Published
2021

22. Launching a multidisciplinary European collaboration towards a cure for HIV: The EU2Cure Consortium.

Author

Rokx, C, Prins, HAB, Vandekerckhove, L, Fidler, SJ, Frater, J, Bracchi, M, Søgaard, OS, Tolstrop, M, Rasmussen, TA, Salgado, M, Blanco, J, Martinez-Picado, J, Clotet, B, Tambussi, G, Groenendijk, A, Verbon, A, Boucher, CAB, Rokx, C, Prins, HAB, Vandekerckhove, L, Fidler, SJ, Frater, J, Bracchi, M, Søgaard, OS, Tolstrop, M, Rasmussen, TA, Salgado, M, Blanco, J, Martinez-Picado, J, Clotet, B, Tambussi, G, Groenendijk, A, Verbon, A, and Boucher, CAB

Abstract

We felt the urgency to launch the EU2Cure Consortium to support research and find a cure for the human immunodeficiency virus (HIV) infection through intensified collaboration within Europe. This consortium is open to stakeholders on cure in Europe from academia and the community to connect. The aim of this consortium is to intensify the research collaboration amongst European HIV cure groups and the community and facilitate interactions with other academic and community cure consortia, private parties, and policy makers. Our main aim is to create a European research agenda, data sharing, and development of best practice for clinical and translational science to achieve breakthroughs with clinically feasible HIV cure strategies. This consortium should also enable setting up collaborative studies accessible to a broader group of people living with HIV. Besides reservoir studies, we have identified three overlapping scientific interests in the consortium that provide a starting point for further research within a European network: developing "shock and kill" cure strategies, defining HIV cure biomarkers, and connecting cure cohorts. This strategy should aid stakeholders to sustain progress in HIV cure research regardless of coincidental global health or political crises.

Published
2021

23. Launching a multidisciplinary European collaboration towards a cure for HIV:The EU2Cure Consortium

Author

Rokx, C., Prins, H. A.B., Vandekerckhove, L., Fidler, S. J., Frater, J., Bracchi, M., Søgaard, O. S., Tolstrop, M., Rasmussen, T. A., Salgado, M., Blanco, J., Martinez-Picado, J., Clotet, B., Tambussi, G., Groenendijk, A., Verbon, A., Boucher, C. A.B., Rokx, C., Prins, H. A.B., Vandekerckhove, L., Fidler, S. J., Frater, J., Bracchi, M., Søgaard, O. S., Tolstrop, M., Rasmussen, T. A., Salgado, M., Blanco, J., Martinez-Picado, J., Clotet, B., Tambussi, G., Groenendijk, A., Verbon, A., and Boucher, C. A.B.

Abstract

We felt the urgency to launch the EU2Cure Consortium to support research and find a cure for the human immunodeficiency virus (HIV) infection through intensified collaboration within Europe. This consortium is open to stakeholders on cure in Europe from academia and the community to connect. The aim of this consortium is to intensify the research collaboration amongst European HIV cure groups and the community and facilitate interactions with other academic and community cure consortia, private parties, and policy makers. Our main aim is to create a European research agenda, data sharing, and development of best practice for clinical and translational science to achieve breakthroughs with clinically feasible HIV cure strategies. This consortium should also enable setting up collaborative studies accessible to a broader group of people living with HIV. Besides reservoir studies, we have identified three overlapping scientific interests in the consortium that provide a starting point for further research within a European network: developing “shock and kill” cure strategies, defining HIV cure biomarkers, and connecting cure cohorts. This strategy should aid stakeholders to sustain progress in HIV cure research regardless of coincidental global health or political crises.

Published
2021

24. Hypothetical questionnaires may overestimate willingness to participate in HIV cure research: Comparison of a cross-sectional survey to actual willingness to participate in an HIV cure study in the Netherlands

Author

Prins, H.A.B., Paulus, M.R., Rokx, C. (Casper), Been, S.K., Verbon, A. (Annelies), Prins, H.A.B., Paulus, M.R., Rokx, C. (Casper), Been, S.K., and Verbon, A. (Annelies)

Abstract

Objective: Little is known about willingness among people living with HIV (PLHIV) to participate in HIV cure research in the Netherlands. We compared results of a cross-sectional questionnaire assessing hypothetical willingness to actual willingness among PLHIV to take part in a clinical HIV cure trial. Methods: Between March and June 2018, PLHIV visiting the outpatient clinic of a university hospital in the Netherlands were asked to complete a questionnaire about HIV cure research. Results were compared to the number of PLHIV willing to take part in an actual HIV cure study at the same center during an overlapping time period. Results: In total, 165 participants, predominantly male (80%) from Western European countries (61%) completed the questionnaire. The majority would participate in cure research (n ¼ 111, 67%). Separately, actual willingness among PLHIV to participate in an HIV cure study was addressed in 312 cases. Apart from gender (96% male), baseline characteristics were comparable. Less than half expressed actual willingness to participate in the study (n ¼ 135, 43%). Conclusions: Hypothetical willingness to participate in cure-related research was high among PLHIV who completed the questionnaire. Actual willingness among eligible PLHIV to take part in an HIV cure study was much lower. Our findings show that questionnaires may overestimate willingness to parti

Published
2020
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25. Inter-Laboratory Reproducibility of Inducible HIV-1 Reservoir Quantification by TILDA

Author

Lungu, C., Procopio, F.A., Overmars, R.J., Beerkens, R.J.J., Voermans, J. (Jolanda), Rao, S., Prins, H.A.B., Rokx, C. (Casper), Pantaleo, G., Vijver, D.A.M.C. (David) van de, Mahmoudi, T., Boucher, C.A.B. (Charles), Gruters, R.A. (Rob), van Kampen, J.J.A., Lungu, C., Procopio, F.A., Overmars, R.J., Beerkens, R.J.J., Voermans, J. (Jolanda), Rao, S., Prins, H.A.B., Rokx, C. (Casper), Pantaleo, G., Vijver, D.A.M.C. (David) van de, Mahmoudi, T., Boucher, C.A.B. (Charles), Gruters, R.A. (Rob), and van Kampen, J.J.A.

Abstract

Substantial efforts to eliminate or reduce latent HIV-1 reservoirs are underway in clinical trials and have created a critical demand for sensitive, accurate, and reproducible tools to evaluate the efficacy of these strategies. Alternative reservoir quantification assays have been developed to circumvent limitations of the quantitative viral outgrowth assay. One such assay is tat/rev induced limiting dilution assay (TILDA), which measures the frequency of CD4+ T cells harboring inducible latent HIV-1 provirus. We modified pre-amplification reagents and conditions (TILDA v2.0) to improve assay execution and first internally validated assay performance using CD4+ T cells obtained from cART-suppressed HIV-1-infected individuals. Detection of tat/rev multiply spliced RNA was not altered by modifying pre-amplification conditions, confirming the robustness of the assay, and supporting the technique’s amenability to limited modifications to ensure better implementation for routine use in clinical studies of latent HIV-1 reservoirs. Furthermore, we cross-validated results of TILDA v2.0 and the original assay performed in two separate laboratories using samples from 15 HIV-1-infected individuals. TILDA and TILDA v2.0 showed a strong correlation (Lin’s Concordance Correlation Coefficient = 0.86). The low inter-laboratory variability between TILDAs performed at different institutes further supports use of TILDA for reservoir quantitation in multi-center interventional HIV-1 Cure trials.

Published
2020
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26. Gliotoxin, identified from a screen of fungal metabolites, disrupts 7SK snRNP, releases P-TEFb, and reverses HIV-1 latency

Author

Stoszko, M.L. (Mateusz), Al-Hatmi, A.M.S., Skriba, A. (Anton), Roling, M. (Michael), Ne, E. (Enrico), Crespo, R. (Raquel), Mueller, Y.M. (Yvonne M.), Najafzadeh, M.J. (Mohammad), Kang, J. (Joyce), Ptackova, R. (Renata), LeMasters, E. (Elizabeth), Biswas, P. (Pritha), Bertoldi, A. (Alessia), Kan, T.W. (Tsung Wai), De Crignis, E. (Elisa), Sulc, M. (Miroslav), Lebbink, J.H.G. (Joyce), Rokx, C. (Casper), Verbon, A. (Annelies), IJcken, W.F.J. (Wilfred) van, Katsikis, P.D. (Peter), Palstra, R.-J.T.S. (Robert-Jan), Havlicek, V. (Vladimir), de Hoog, S. (Sybren), Mahmoudi, T. (Tokameh), Stoszko, M.L. (Mateusz), Al-Hatmi, A.M.S., Skriba, A. (Anton), Roling, M. (Michael), Ne, E. (Enrico), Crespo, R. (Raquel), Mueller, Y.M. (Yvonne M.), Najafzadeh, M.J. (Mohammad), Kang, J. (Joyce), Ptackova, R. (Renata), LeMasters, E. (Elizabeth), Biswas, P. (Pritha), Bertoldi, A. (Alessia), Kan, T.W. (Tsung Wai), De Crignis, E. (Elisa), Sulc, M. (Miroslav), Lebbink, J.H.G. (Joyce), Rokx, C. (Casper), Verbon, A. (Annelies), IJcken, W.F.J. (Wilfred) van, Katsikis, P.D. (Peter), Palstra, R.-J.T.S. (Robert-Jan), Havlicek, V. (Vladimir), de Hoog, S. (Sybren), and Mahmoudi, T. (Tokameh)

Abstract

A leading pharmacological strategy toward HIV cure requires "shock" or activation of HIV gene expression in latently infected cells with latency reversal agents (LRAs) followed by their subsequent clearance. In a screen for novel LRAs, we used fungal secondary metabolites as a source of bioactive molecules. Using orthogonal mass spectrometry (MS) coupled to latency reversal bioassays, we identified gliotoxin (GTX) as a novel LRA. GTX significantly induced HIV-1 gene expression in latent ex vivo infected primary cells and in CD4+ T cells from all aviremic HIV-1+ participants. RNA sequencing identified 7SK RNA, the scaffold of the positive transcription elongation factor b (P-TEFb) inhibitory 7SK small nuclear ribonucleoprotein (snRNP) complex, to be significantly reduced upon GTX treatment of CD4+ T cells. GTX directly disrupted 7SK snRNP by targeting La-related protein 7 (LARP7), releasing active P-TEFb, which phosphorylated RNA polymerase II (Pol II) C-terminal domain (CTD), inducing HIV transcription.

Published
2020
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28. Risk of recurrent venous thromboembolism in patients with HIV infection: A nationwide cohort study

Author

Rokx, C. (Casper), Howard, J.F.B. (Jaime F. Borjas), Smit, C. (Colette), Wit, F.W.N.M. (Ferdinand), Pieterman, E.D. (Elise), Reiss, P. (Peter), Cannegieter, S.C. (Suzanne), Lijfering, W.M., Meijer, K. (Karina), Bierman, W.F.W. (Wouter), Tichelaar, V. (Vladimir), Rijnders, B.J.A. (Bart), Rokx, C. (Casper), Howard, J.F.B. (Jaime F. Borjas), Smit, C. (Colette), Wit, F.W.N.M. (Ferdinand), Pieterman, E.D. (Elise), Reiss, P. (Peter), Cannegieter, S.C. (Suzanne), Lijfering, W.M., Meijer, K. (Karina), Bierman, W.F.W. (Wouter), Tichelaar, V. (Vladimir), and Rijnders, B.J.A. (Bart)

Abstract

Background Multiple studies have described a higher incidence of venous thromboembolism (VTE) in people living with an HIV infection (PWH). However, data on the risk of recurrent VTE in this population are lacking, although this question is more important for clinical practice. This study aims to estimate the risk of recurrent VTE in PWH compared to controls and to identify risk factors for recurrence within this population. Methods and findings PWH with a first VTE were derived from the AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort (2003-2015), a nationwide ongoing cohort following up PWH in care in the Netherlands. Uninfected controls were derived from the Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis (MEGA) follow-up study (1999-2003), a cohort of patients with a first VTE who initially participated in a case-control study in the Netherlands who were followed up for recurrent VTE. Selection was limited to persons with an index VTE suffering from deep vein thrombosis in the lower limbs and/or pulmonary embolism (PE). Participants were followed from withdrawal of anticoagulation to VTE recurrence, loss to follow-up, death, or end of study. We estimated incidence rates, cumulative incidence (accounting for competing risk of death) and hazard ratios (HRs) using Cox proportional hazards regression, adjusting for age, sex, and whether the index event was p

Published
2020
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29. An evaluation of COVID-19 serological assays informs future diagnostics and exposure assessment

Author

Geurts van Kessel, C.H. (Corine), Okba, N.M.A. (Nisreen), Igloi, Z. (Zsofia), Bogers, S. (Susanne), Embregts, C.W.E. (Carmen W. E.), Laksono, B.M. (Brigitta), Leijten, L.M.E. (Lonneke), Rokx, C. (Casper), Rijnders, B.J.A. (Bart), Rahamat-Langendoen, J. (Janette), Van Den Akker, J.P.C., Kampen, J.J.A. (Jeroen) van, Eijck, A.A. (Annemiek), Binnendijk, R.S. (Rob) van, Haagmans, B.L. (Bart), Koopmans D.V.M., M.P.G. (Marion), Geurts van Kessel, C.H. (Corine), Okba, N.M.A. (Nisreen), Igloi, Z. (Zsofia), Bogers, S. (Susanne), Embregts, C.W.E. (Carmen W. E.), Laksono, B.M. (Brigitta), Leijten, L.M.E. (Lonneke), Rokx, C. (Casper), Rijnders, B.J.A. (Bart), Rahamat-Langendoen, J. (Janette), Van Den Akker, J.P.C., Kampen, J.J.A. (Jeroen) van, Eijck, A.A. (Annemiek), Binnendijk, R.S. (Rob) van, Haagmans, B.L. (Bart), and Koopmans D.V.M., M.P.G. (Marion)

Abstract

The world is entering a new era of the COVID-19 pandemic in which there is an increasing call for reliable antibody testing. To support decision making on the deployment of serology for either population screening or diagnostics, we present a detailed comparison of serological COVID-19 assays. We show that among the selected assays there is a wide diversity in assay performance in different scenarios and when correlated to virus neutralizing antibodies. The Wantai ELISA detecting total immunoglobulins against the receptor binding domain of SARS CoV-2, has the best overall characteristics to detect functional antibodies in different stages and severity of disease, including the potential to set a cut-off indicating the presence of protective antibodies. The large variety of available serological assays requires proper assay validation before deciding on deployment of assays for specific applications.

Published
2020
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31. Increased Virological Failure in Naive HIV-1-Infected Patients Taking Lamivudine Compared With Emtricitabine in Combination with Tenofovir and Efavirenz or Nevirapine in the Dutch Nationwide ATHENA cohort

Author

Rokx, C., Fibriani, A., Vijver, D.A. van de, Verbon, A., Schutten, M., Gras, L., Rijnders, B.J., Koopmans †, P.P., Keuter, M., Ven, A.J.A.M. van der, Hofstede, H.J.M. ter, Dofferhoff, A.S.M., Warris, A., Crevel, R. van, Internal Medicine, Virology, Med Microbiol, Infect Dis & Infect Prev, RS: CAPHRI School for Public Health and Primary Care, Graduate School, Amsterdam institute for Infection and Immunity, Infectious diseases, Paediatric Infectious Diseases / Rheumatology / Immunology, Global Health, General Internal Medicine, Amsterdam Public Health, Center of Experimental and Molecular Medicine, and Other departments

Subjects
Microbiology (medical), Adult, Male, medicine.medical_specialty, Nevirapine, Efavirenz, lnfectious Diseases and Global Health Radboud Institute for Molecular Life Sciences [Radboudumc 4], HIV Infections, Emtricitabine, Cohort Studies, chemistry.chemical_compound, SDG 3 - Good Health and Well-being, immune system diseases, Internal medicine, Antiretroviral Therapy, Highly Active, medicine, Humans, Treatment Failure, Netherlands, business.industry, Incidence, Hazard ratio, Lamivudine, virus diseases, Odds ratio, Middle Aged, Viral Load, Virology, Infectious Diseases, lnfectious Diseases and Global Health Radboud Institute for Health Sciences [Radboudumc 4], chemistry, Anti-Retroviral Agents, Cohort, HIV-1, Female, business, Viral load, medicine.drug
Abstract

Contains fulltext : 153151.pdf (Publisher’s version ) (Closed access) BACKGROUND: Guidelines for treatment of human immunodeficiency virus type 1 (HIV-1) infection consider lamivudine and emtricitabine to be interchangeable components in first-line combination antiretroviral therapy (cART). The evidence for their clinical equivalence in cART is inconsistent. The primary aim of this study was to evaluate the virological responses to lamivudine and emtricitabine in recommended cART. METHODS: This was an observational study using data from the AIDS Therapy Evaluation in the Netherlands (ATHENA) nationwide HIV cohort. The virological responses to lamivudine and emtricitabine were compared by multivariable adjusted logistic regression and Cox proportional hazard models. Sensitivity analyses included propensity score-adjusted models. RESULTS: Therapy-naive HIV-1-infected patients without baseline resistance (N = 4740) initiated lamivudine or emtricitabine with efavirenz/tenofovir or nevirapine/tenofovir. The use of lamivudine was associated with more virological failure at week 48 compared to emtricitabine with efavirenz/tenofovir (10.8% vs 3.6%; adjusted odds ratio [AOR], 1.78; 95% confidence interval [CI], 1.11-2.84) and nevirapine/tenofovir (27% vs 11%; AOR, 2.09; 95% CI, 1.25-3.52) in on-treatment analysis. Propensity score-adjusted models and intent-to-treat sensitivity analyses gave comparable results. The adjusted hazard ratio of virological failure at week 240 using lamivudine instead of emtricitabine was 2.35 (95% CI, 1.61-3.42) with efavirenz and 2.01 (95% CI, 1.36-2.98) with nevirapine. The inclusion of lamivudine or emtricitabine in cART did not influence the time to virological suppression within 48 weeks or the probability of virological rebound after successful virological suppression. CONCLUSIONS: The use of emtricitabine instead of lamivudine as part of cART was associated with better virological responses. These findings are relevant for settings with extensive use of lamivudine and for settings where generic lamivudine will be available.

Published
2015

33. Mutational correlates of virological failure in individuals receiving a WHO-recommended tenofovir-containing first-line regimen: An international collaboration

Author

Rhee, S.Y. (Soo Yoon), Varghese, V. (Vici), Holmes, S.P. (Susan P.), Van Zyl, G.U. (Gert U.), Steegen, K. (Kim), Boyd, M.A. (Mark A.), Cooper, D.A. (David), Nsanzimana, S. (Sabin), Saravanan, S. (Shanmugam), Charpentier, C. (Charlotte), Oliveira, T. (Tulio) de, Etiebet, M.A.A. (Mary-Ann A.), Garcia, F., Goedhals, D., Gomes, P. (Perpetua), Günthard, H.F., Hamers, R.L. (Raph), Hoffmann, C.J. (Christopher J), Hunt, G.M. (Gillian M.), Jiamsakul, A. (Awachana), Kaleebu, P. (Pontiano), Kanki, P.J., Kantor, R. (Rami), Kerschberger, B., Marconi, V.C., D'amour Ndahimana, J. (Jean), Ndembi, N. (Nicaise), Ngo-Giang-Huong, N. (Nicole), Rokx, C. (Casper), Santoro, M.M. (Maria), Schapiro, J.M. (Jonathan), Schmidt, D., Seu, L. (Lillian), Sigaloff, K.C. (Kim), Sirivichayakul, S. (Sunee), Skhosana, L. (Lindiwe), Sunpath, H., Tang, M., Yang, C. (Chunfu), Carmona, S. (Sergio), Gupta, R.K. (Ravindra K.), Shafer, R.W. (Robert), Rhee, S.Y. (Soo Yoon), Varghese, V. (Vici), Holmes, S.P. (Susan P.), Van Zyl, G.U. (Gert U.), Steegen, K. (Kim), Boyd, M.A. (Mark A.), Cooper, D.A. (David), Nsanzimana, S. (Sabin), Saravanan, S. (Shanmugam), Charpentier, C. (Charlotte), Oliveira, T. (Tulio) de, Etiebet, M.A.A. (Mary-Ann A.), Garcia, F., Goedhals, D., Gomes, P. (Perpetua), Günthard, H.F., Hamers, R.L. (Raph), Hoffmann, C.J. (Christopher J), Hunt, G.M. (Gillian M.), Jiamsakul, A. (Awachana), Kaleebu, P. (Pontiano), Kanki, P.J., Kantor, R. (Rami), Kerschberger, B., Marconi, V.C., D'amour Ndahimana, J. (Jean), Ndembi, N. (Nicaise), Ngo-Giang-Huong, N. (Nicole), Rokx, C. (Casper), Santoro, M.M. (Maria), Schapiro, J.M. (Jonathan), Schmidt, D., Seu, L. (Lillian), Sigaloff, K.C. (Kim), Sirivichayakul, S. (Sunee), Skhosana, L. (Lindiwe), Sunpath, H., Tang, M., Yang, C. (Chunfu), Carmona, S. (Sergio), Gupta, R.K. (Ravindra K.), and Shafer, R.W. (Robert)

Abstract

Tenofovir disoproxil fumarate (TDF) genotypic resistance defined by K65R/N and/or K70E/Q/G occurs in 20% to 60% of individuals with virological failure (VF) on a WHO-recommended TDF-containing first-line regimen. However, the full spectrum of reverse transcriptase (RT) mutations selected in individuals with VF on such a regimen is not known. To identify TDF regimen-associated mutations (TRAMs), we compared the proportion of each RT mutation in 2873 individuals with VF on a WHO-recommended first-line TDF-containing regimen to its proportion in a cohort of 50,803 antiretroviral-naïve individuals. To identify TRAMs specifically associated with TDF-selection pressure, we compared the proportion of each TRAM to its proportion in a cohort of 5805 individuals with VF on a first-line thymidine analog-containing regimen. We identified 83 TRAMs including 33 NRTI-associated, 40 NNRTI-associated, and 10 uncommon mutations of uncertain provenance. Of the 33 NRTI-associated TRAMs, 12 - A62V, K65R/N, S68G/N/D, K70E/Q/T, L74I, V75L, and Y115F - were more common a

Published
2017
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34. Ending the epidemic:Critical role of primary HIV infection

Author

Prins, H A B, Verbon, A, Boucher, C A B, Rokx, C, Prins, H A B, Verbon, A, Boucher, C A B, and Rokx, C

Abstract

Early identification and immediate treatment of individuals newly infected with HIV is important for two reasons: it benefits the long-term health of the infected patient, and it reduces onward HIV transmission. Primary HIV infection (PHI) reflects the period following HIV acquisition during which viraemia bursts until the establishment of a stable plasma HIV-RNA level approximately six months post infection. During this period, patients are particularly contagious and are often unaware of the infection. As a consequence, PHI disproportionally affects onward transmission. During PHI the immune system is irreparably damaged and persistent viral reservoirs are formed. Initiating antiretroviral therapy (ART) during PHI could potentially lead to a functional cure through early and prolonged viral suppression. Unfortunately, symptoms of PHI are nonspecific and the diagnosis is frequently missed. This impedes timely diagnosis and prompt initiation of ART. To increase awareness and underscore the importance of immediate ART initiation, we describe here the pathogenesis, clinical presentation, and impact of treating PHI.

Published
2017

35. Global epidemiology of drug resistance after failure of WHO recommended first-line regimens for adult HIV-1 infection: a multicentre retrospective cohort study

Author

Gregson, J, Tang, M, Ndembi, N, Hamers, Rl, Marconi, Vc, Brooks, K, Theys, K, Arruda, M, Garcia, F, Monge, S, Kanki, Pj, Kumarasamy, N, Kerschberger, B, Mor, O, Charpentier, C, Todesco, E, Rokx, C, Gras, L, Halvas, Ek, Sunpath, H, Carlo, Dd, Antinori, A, Andreoni, M, Latini, A, Mussini, C, Aghokeng, A, Sonnerborg, A, Neogi, U, Fessel, Wj, Agolory, S, Yang, C, Blanco, Jl, Juma, Jm, Smit, E, Schmidt, D, Watera, C, Asio, J, Kirungi, W, Tostevin, A, Clumeck, N, Goedhals, D, Bester, Pa, Sabin, C, Mukui, I, Santoro, M, Perno, Cf, Hunt, G, Morris, L, Pillay, D, Schulter, E, Reyes-Teran, G, Romero, K, Avila-Rios, S, Sirivichayakul, S, Ruxrungtham, K, Mekprasan, S, Dunn, D, Kaleebu, P, Raizes, E, Kantor, R, Gupta, Rk, Rhee, S, Shafer, Rw, de Wit, Tfr, Diero, L, Camacho, R, Gunthard, Hf, Hoffmann, Cj, Di Carlo, D, El-Hay, T, van Vuuren, C, de Oliveira, T, Murakami-Ogasawara, A, [Pillay, Deenan] UCL, Dept Infect, London WC1E 6BT, England, [Gupta, Ravindra K.] UCL, Dept Infect, London WC1E 6BT, England, [Tang, Michele] Stanford Univ, Dept Med, Stanford, CA 94305 USA, [Rhee, Soo-Yon] Stanford Univ, Dept Med, Stanford, CA 94305 USA, [Shafer, Robert W.] Stanford Univ, Dept Med, Stanford, CA 94305 USA, [Gregson, John] London Sch Hyg & Trop Med, Dept Stat, London, England, [Ndembi, Nicaise] Inst Human Virol Nigeria, Abuja, Federal Capital, Nigeria, [Hamers, Raph L.] Univ Amsterdam, Acad Med Ctr, Amsterdam Inst Global Hlth & Dev, Dept Global Hlth, NL-1012 WX Amsterdam, Netherlands, [de Wit, Tobias F. Rinke] Univ Amsterdam, Acad Med Ctr, Amsterdam Inst Global Hlth & Dev, Dept Global Hlth, NL-1012 WX Amsterdam, Netherlands, [Hamers, Raph L.] Univ Amsterdam, Acad Med Ctr, Dept Internal Med, NL-1012 WX Amsterdam, Netherlands, [de Wit, Tobias F. Rinke] Univ Amsterdam, Acad Med Ctr, Dept Internal Med, NL-1012 WX Amsterdam, Netherlands, [Marconi, Vincent C.] Emory Univ, Rollins Sch Publ Hlth, Dept Global Hlth, Atlanta, GA 30322 USA, [Marconi, Vincent C.] Emory Univ, Sch Med, Div Infect Dis, Atlanta, GA USA, [Diero, Lameck] Moi Univ, Eldoret, Kenya, [Diero, Lameck] Acad Model Providing Access Healthcare, Eldoret, Kenya, [Brooks, Katherine] Brown Univ, Alpert Med Sch, Div Infect Dis, Providence, RI 02912 USA, [Theys, Kristof] KU Leuven Univ Leuven, Rega Inst Med Res, Dept Microbiol & Immunol, B-3000 Leuven, Belgium, [Camacho, Ricardo] KU Leuven Univ Leuven, Rega Inst Med Res, Dept Microbiol & Immunol, B-3000 Leuven, Belgium, [Kantor, Rami] KU Leuven Univ Leuven, Rega Inst Med Res, Dept Microbiol & Immunol, B-3000 Leuven, Belgium, [Arruda, Monica] Univ Fed Rio de Janeiro, Inst Biol, LVM, BR-21941 Rio De Janeiro, Brazil, [Garcia, Frederico] Complejo Hosp Univ Granada, Granada, Spain, Univ Alcala de Henares, E-28871 Alcala De Henares, Spain, [Monge, Susana] CIBERESP, Madrid, Spain, [Gunthard, Huldrych F.] Univ Zurich, Div Infect Dis & Hosp Epidemiol, Zurich, Switzerland, [Gunthard, Huldrych F.] Univ Zurich, Inst Med Virol, Zurich, Switzerland, [Hoffmann, Christopher J.] Johns Hopkins Univ, Baltimore, MD USA, [Hoffmann, Christopher J.] Aurum Inst, Johannesburg, South Africa, [Kanki, Phyllis J.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA, [Kumarasamy, Nagalingeshwaran] VHS, YRGCARE Med Ctr, Chennai, Tamil Nadu, India, [Kerschberger, Bernard] Med Sans Frontieres Operat Ctr Geneva, Mbabane, Eswatini, [Mor, Orna] Israel Minist Hlth, Publ Hlth Serv, Cent Virol Lab, Jerusalem, Israel, [Charpentier, Charlotte] Univ Paris Diderot, Sorbonne Paris Cite, IAME, UMR 1137, Paris, France, [Charpentier, Charlotte] INSERM, IAME, UMR 1137, Paris, France, [Charpentier, Charlotte] Hop Bichat Claude Bernard, AP HP, Virol Lab, F-75018 Paris, France, [Todesco, Eva] Hop La Pitie Salpetriere, Lab Virol, Paris, France, [Rokx, Casper] Erasmus Univ, Med Ctr, Dept Internal Med Infect Dis, Rotterdam, Netherlands, [Gras, Luuk] Stichting HIV Monitoring, Amsterdam, Netherlands, [Halvas, Elias K.] Univ Pittsburgh, Pittsburgh, PA USA, [Sunpath, Henry] Ethekwini Dist Hlth Off, Kwa Zulu, South Africa, [Di Carlo, Domenico] Univ Roma Tor Vergata, Dept Expt Med & Surg, Rome, Italy, [Santoro, Maria M.] Univ Roma Tor Vergata, Dept Expt Med & Surg, Rome, Italy, [Antinori, Antonio] INMI L Spallanzani, Infect Dis Unit, Rome, Italy, [Andreoni, Massimo] Univ Hosp Tor Vergata, Clin Infect Dis, Rome, Italy, [Latini, Alessandra] San Gallicano Dermatol Inst, HIV AIDS Unit, Rome, Italy, [Mussini, Cristina] Azienda Osped Univ Policlin, Clin Infect Dis, Modena, Italy, [Aghokeng, Avelin] Virol Lab CREMER IMPM, Yaounde, Cameroon, [Sonnerborg, Anders] Karolinska Inst, Div Clin Microbiol, Stockholm, Sweden, [Neogi, Ujjwal] Karolinska Inst, Div Clin Microbiol, Stockholm, Sweden, [Sonnerborg, Anders] Karolinska Inst, Infect Dis Unit, Stockholm, Sweden, [Neogi, Ujjwal] Karolinska Inst, Infect Dis Unit, Stockholm, Sweden, [Sonnerborg, Anders] Karolinska Univ Hosp, Stockholm, Sweden, [Neogi, Ujjwal] Karolinska Univ Hosp, Stockholm, Sweden, [Fessel, William J.] Kaiser Permanente Med Care Program Northern Calif, San Francisco, CA USA, [Agolory, Simon] Ctr Dis Control & Prevent, Div Global HIV AIDS, Ctr Global Hlth, Atlanta, GA USA, [Raizes, Elliot] Ctr Dis Control & Prevent, Div Global HIV AIDS, Ctr Global Hlth, Atlanta, GA USA, [Yang, Chunfu] Ctr Dis Control & Prevent, Int Lab Branch, Div Global HIV AIDS, Ctr Global Hlth, Atlanta, GA USA, [Blanco, Jose L.] Univ Barcelona, Inst Invest Biomed August Pi i Sunyer, Clin Univ, Barcelona, Spain, [Juma, James M.] Minist Hlth & Social Welf, Dar Es Salaam, Tanzania, [Smit, Erasmus] Publ Hlth England, Publ Hlth Lab, Birmingham, W Midlands, England, [Schmidt, Daniel] Robert Koch Inst, Dept Infect Dis Epidemiol HIV AIDS STI & Blood Bo, Berlin, Germany, [Watera, Christine] Uganda Res Unit AIDS, Entebbe, Uganda, [Asio, Juliet] Uganda Res Unit AIDS, Entebbe, Uganda, [Kaleebu, Pontiano] Uganda Res Unit AIDS, Entebbe, Uganda, [Tostevin, Anna] Minist Hlth, Kampala, Uganda, [Tostevin, Anna] UCL, MRC Clin Trials Unit, London, England, [Dunn, David] UCL, MRC Clin Trials Unit, London, England, [El-Hay, Tal] IBM Haifa Res Lab, Haifa, Israel, [Clumeck, Nathan] Univ Libre Bruxelles, St Pierre Univ Hosp, Brussels, Belgium, [Goedhals, Dominique] Univ Orange Free State, Dept Med Microbiol & Virol, Natl Hlth Lab Serv, Bloemfontein, South Africa, [van Vuuren, Cloete] Univ Orange Free State, Dept Med Microbiol & Virol, Natl Hlth Lab Serv, Bloemfontein, South Africa, [Sabin, Caroline] UCL, Infect & Populat Hlth, London, England, [Mukui, Irene] Minist Hlth, Natl AIDS & STI Control Programme, Nairobi, Kenya, [Perno, Carlo F.] INMI L Spallanzani, Antiretroviral Drugs Monitoring Unit, Rome, Italy, [Hunt, Gillian] Natl Inst Communicable Dis, Johannesburg, South Africa, [Morris, Lynn] Natl Inst Communicable Dis, Johannesburg, South Africa, [de Oliveira, Tulio] Wellcome Trust Africa Ctr Hlth & Populat Studies, Durban, South Africa, [Pillay, Deenan] Wellcome Trust Africa Ctr Hlth & Populat Studies, Durban, South Africa, [de Oliveira, Tulio] Univ KwaZulu Natal, Coll Hlth Sci, Durban, South Africa, [Schulter, Eugene] Univ Cologne, Inst Virol, D-50931 Cologne, Germany, [Murakami-Ogasawara, Akio] Natl Inst Resp Dis, Ctr Res Infect Dis, Mexico City, DF, Mexico, [Sirivichayakul, Sunee] Chulalongkorn Univ, Dept Med, Bangkok, Thailand, [Ruxrungtham, Kiat] Chulalongkorn Univ, Dept Med, Bangkok, Thailand, [Mekprasan, Suwanna] Chulalongkorn Univ, Dept Med, Bangkok, Thailand, [Kaleebu, Pontiano] MRC UVRI Uganda Res Unit AIDS, Entebbe, Uganda, Wellcome Trust, MRC, NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES, and Medical Research Council

Subjects
Cyclopropanes, Anti-HIV Agents, K65r, Drug Resistance, Antiretroviral Therapy, HIV Infections, Global Health, Settore MED/07, Virological failure, Tenofovir disoproxil fumarate, Antiretroviral Therapy, Highly Active, Drug Resistance, Viral, Humans, Emtricitabine, Transmission, Highly Active, Viral, Tenofovir, Africa South of the Sahara, Benzoxazines, HIV-1, Lamivudine, Pre-Exposure Prophylaxis, Retrospective Studies, Reverse Transcriptase Inhibitors, Viral Load, Hiv-1-infected patients, virus diseases, Articles, Antiretroviral therapy, Naive patients, Alkynes, Efavirenz
Abstract

Summary Background Antiretroviral therapy (ART) is crucial for controlling HIV-1 infection through wide-scale treatment as prevention and pre-exposure prophylaxis (PrEP). Potent tenofovir disoproxil fumarate-containing regimens are increasingly used to treat and prevent HIV, although few data exist for frequency and risk factors of acquired drug resistance in regions hardest hit by the HIV pandemic. We aimed to do a global assessment of drug resistance after virological failure with first-line tenofovir-containing ART. Methods The TenoRes collaboration comprises adult HIV treatment cohorts and clinical trials of HIV drug resistance testing in Europe, Latin and North America, sub-Saharan Africa, and Asia. We extracted and harmonised data for patients undergoing genotypic resistance testing after virological failure with a first-line regimen containing tenofovir plus a cytosine analogue (lamivudine or emtricitabine) plus a non-nucleotide reverse-transcriptase inhibitor (NNRTI; efavirenz or nevirapine). We used an individual participant-level meta-analysis and multiple logistic regression to identify covariates associated with drug resistance. Our primary outcome was tenofovir resistance, defined as presence of K65R/N or K70E/G/Q mutations in the reverse transcriptase (RT) gene. Findings We included 1926 patients from 36 countries with treatment failure between 1998 and 2015. Prevalence of tenofovir resistance was highest in sub-Saharan Africa (370/654 [57%]). Pre-ART CD4 cell count was the covariate most strongly associated with the development of tenofovir resistance (odds ratio [OR] 1·50, 95% CI 1·27–1·77 for CD4 cell count

Published
2016

36. Global epidemiology of drug resistance after failure of WHO recommended first-line regimens for adult HIV-1 infection: a multicentre retrospective cohort study

Author

Gregson, J, Tang, M, Ndembi, N, Hamers, R, Marconi, V, Brooks, K, Theys, K, Arruda, M, Garcia, F, Monge, S, Kanki, P, Kumarasamy, N, Kerschberger, B, Mor, O, Charpentier, C, Todesco, E, Rokx, C, Gras, L, Halvas, E, Sunpath, H, Carlo, D, Antinori, A, Andreoni, M, Latini, A, Mussini, C, Aghokeng, A, Sonnerborg, A, Neogi, U, Fessel, W, Agolory, S, Yang, C, Blanco, J, Juma, J, Smit, E, Schmidt, D, Watera, C, Asio, J, Kirungi, W, Tostevin, A, Clumeck, N, Goedhals, D, Bester, P, Sabin, C, Mukui, I, Santoro, M, Perno, C, Hunt, G, Morris, L, Camacho, R, Pillay, D, Schulter, E, Reyes-Terán, G, Romero, K, Avila-Rios, S, Sirivichayakul, S, Ruxrungtham, K, Mekprasan, S, Dunn, D, Kaleebu, P, Raizes, E, Kantor, R, Shafer, R, Gupta, R, Rhee, S, De Wit, T, Diero, L, Günthard, H, Hoffmann, C, and Di Carlo, D

Subjects
virus diseases
Abstract

Background Antiretroviral therapy (ART) is crucial for controlling HIV-1 infection through wide-scale treatment as prevention and pre-exposure prophylaxis (PrEP). Potent tenofovir disoproxil fumarate-containing regimens are increasingly used to treat and prevent HIV, although few data exist for frequency and risk factors of acquired drug resistance in regions hardest hit by the HIV pandemic. We aimed to do a global assessment of drug resistance after virological failure with first-line tenofovir-containing ART. Methods The TenoRes collaboration comprises adult HIV treatment cohorts and clinical trials of HIV drug resistance testing in Europe, Latin and North America, sub-Saharan Africa, and Asia. We extracted and harmonised data for patients undergoing genotypic resistance testing after virological failure with a first-line regimen containing tenofovir plus a cytosine analogue (lamivudine or emtricitabine) plus a non-nucleotide reverse-transcriptase inhibitor (NNRTI; efavirenz or nevirapine). We used an individual participant-level meta-analysis and multiple logistic regression to identify covariates associated with drug resistance. Our primary outcome was tenofovir resistance, defined as presence of K65R/N or K70E/G/Q mutations in the reverse transcriptase (RT) gene. Findings We included 1926 patients from 36 countries with treatment failure between 1998 and 2015. Prevalence of tenofovir resistance was highest in sub-Saharan Africa (370/654 [57%]). Pre-ART CD4 cell count was the covariate most strongly associated with the development of tenofovir resistance (odds ratio [OR] 1·50, 95% CI 1·27–1·77 for CD4 cell count

Published
2015

37. Virological responses to lamivudine or emtricitabine when combined with tenofovir and a protease inhibitor in treatment-naïve HIV-1-infected patients in the Dutch AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort

Author

Rokx, C., Gras, L., van de Vijver, D. A M C, Verbon, A., Rijnders, B. J A, Prins, J. M., Kuijpers, T. W., Scherpbier, H. J., van der Meer, J. T M, Wit, F. W M N, Godfried, M. H., Reiss, P., van der Poll, T., Nellen, F. J B, Lange, J. M A, Geerlings, S. E., van Vugt, M., Pajkrt, D., Bos, J. C., van der Valk, M, Wiersinga, W. J., Goorhuis, A., Hovius, J. W R, Lowe, S., Oude Lashof, A., Posthouwer, D., Pronk, M. J H, Ammerlaan, H. S M, van der Ende, M. E., de Vries-Sluijs, T. E M S, Schurink, C. A M, Nouwen, J. L., van Gorp, E. C M, van der Feltz, M., Driessen, G. J A, van Rossum, A. M C, Branger, J., Schippers, E. F., van Nieuwkoop, C., van Elzakker, E. P., Groeneveld, P. H P, Bouwhuis, J. W., Soetekouw, R., ten Kate, R. W., Kroon, F. P., van Dissel, J. T., Arend, S. M., de Boer, M. G J, Jolink, H., Vollaard, A. M., Bauer, M. P., den Hollander, J. G., Pogany, K., van Twillert, G., Kortmann, W., Cohen Stuart, J. W T, Diederen, B. M W, Leyten, E. M S, Gelinck, L. B S, Kootstra, G. J., Delsing, C. E., Brinkman, K., Blok, W. L., Frissen, P. H J, Schouten, W. E M, van den Berk, G. E L, van Kasteren, M. E E, Brouwer, A.E., Veenstra, J., Lettinga, K. D., Mulder, J. W., Vrouenraets, S. M E, Lauw, F. N., van Eeden, A., Verhagen, D. W M, Sprenger, H. G., Scholvinck, E. H., van Assen, S., Bierman, W. F W, Wilting, K. R., Stienstra, Y., Koopmans, P. P., Keuter, M., van der Ven, A. J A M, ter Hofstede, H. J M, Dofferhoff, A. S M, Warris, A., van Crevel, R., Hoepelman, A. I M, Mudrikova, T., Schneider, M. M E, Ellerbroek, P. M., Oosterheert, J. J., Arends, J. E., Wassenberg, M. W M, Barth, R. E., van Agtmael, M. A., Perenboom, R. M., Claessen, F. A P, Bomers, M., Peters, E.J.G., Geelen, S. P M, Wolfs, T. F W, Bont, L. J., Richter, C., van der Berg, J. P., Gisolf, E. H., van den Berge, M., Stegeman, A., van Vonderen, M. G A, van Houte, D. P F, Weijer, S., el Moussaoui, R., Winkel, C., Muskiet, F., Durand, A., Voigt, R., Rokx, C., Gras, L., van de Vijver, D. A M C, Verbon, A., Rijnders, B. J A, Prins, J. M., Kuijpers, T. W., Scherpbier, H. J., van der Meer, J. T M, Wit, F. W M N, Godfried, M. H., Reiss, P., van der Poll, T., Nellen, F. J B, Lange, J. M A, Geerlings, S. E., van Vugt, M., Pajkrt, D., Bos, J. C., van der Valk, M, Wiersinga, W. J., Goorhuis, A., Hovius, J. W R, Lowe, S., Oude Lashof, A., Posthouwer, D., Pronk, M. J H, Ammerlaan, H. S M, van der Ende, M. E., de Vries-Sluijs, T. E M S, Schurink, C. A M, Nouwen, J. L., van Gorp, E. C M, van der Feltz, M., Driessen, G. J A, van Rossum, A. M C, Branger, J., Schippers, E. F., van Nieuwkoop, C., van Elzakker, E. P., Groeneveld, P. H P, Bouwhuis, J. W., Soetekouw, R., ten Kate, R. W., Kroon, F. P., van Dissel, J. T., Arend, S. M., de Boer, M. G J, Jolink, H., Vollaard, A. M., Bauer, M. P., den Hollander, J. G., Pogany, K., van Twillert, G., Kortmann, W., Cohen Stuart, J. W T, Diederen, B. M W, Leyten, E. M S, Gelinck, L. B S, Kootstra, G. J., Delsing, C. E., Brinkman, K., Blok, W. L., Frissen, P. H J, Schouten, W. E M, van den Berk, G. E L, van Kasteren, M. E E, Brouwer, A.E., Veenstra, J., Lettinga, K. D., Mulder, J. W., Vrouenraets, S. M E, Lauw, F. N., van Eeden, A., Verhagen, D. W M, Sprenger, H. G., Scholvinck, E. H., van Assen, S., Bierman, W. F W, Wilting, K. R., Stienstra, Y., Koopmans, P. P., Keuter, M., van der Ven, A. J A M, ter Hofstede, H. J M, Dofferhoff, A. S M, Warris, A., van Crevel, R., Hoepelman, A. I M, Mudrikova, T., Schneider, M. M E, Ellerbroek, P. M., Oosterheert, J. J., Arends, J. E., Wassenberg, M. W M, Barth, R. E., van Agtmael, M. A., Perenboom, R. M., Claessen, F. A P, Bomers, M., Peters, E.J.G., Geelen, S. P M, Wolfs, T. F W, Bont, L. J., Richter, C., van der Berg, J. P., Gisolf, E. H., van den Berge, M., Stegeman, A., van Vonderen, M. G A, van Houte, D. P F, Weijer, S., el Moussaoui, R., Winkel, C., Muskiet, F., Durand, A., and Voigt, R.

Published
2016

38. Small Molecule Inhibitors of BAF; A Promising Family of Compounds in HIV-1 Latency Reversal

Author

Stoszko, M.L. (Mateusz), De Crignis, E. (Elisa), Rokx, C. (Casper), Khalid, M.M. (Mir Mubashir), Lungu, C. (Cynthia), Palstra, R.-J.T.S. (Robert-Jan), Kan, T.W. (Tsung Wai), Boucher, C.A.B. (Charles), Verbon, A. (Annelies), Dykhuizen, E.C. (Emily C.), Mahmoudi, T. (Tokameh), Stoszko, M.L. (Mateusz), De Crignis, E. (Elisa), Rokx, C. (Casper), Khalid, M.M. (Mir Mubashir), Lungu, C. (Cynthia), Palstra, R.-J.T.S. (Robert-Jan), Kan, T.W. (Tsung Wai), Boucher, C.A.B. (Charles), Verbon, A. (Annelies), Dykhuizen, E.C. (Emily C.), and Mahmoudi, T. (Tokameh)

Abstract

Persistence of latently infected cells in presence of Anti-Retroviral Therapy presents the main obstacle to HIV-1 eradication. Much effort is thus placed on identification of compounds capable of HIV-1 latency reversal in order to render infected cells susceptible to viral cytopathic effects and immune clearance. We identified the BAF chromatin remodeling complex as a key player required for maintenance of HIV-1 latency, highlighting its potential as a molecular target for inhibition in latency reversal. Here, we screened a recently identified panel of small molecule inhibitors of BAF (BAFi's) for potential to activate latent HIV-1. Latency reversal was strongly induced by BAFi's Caffeic Acid Phenethyl Ester and Pyrimethamine, two molecules previously characterized for clinical application. BAFi's reversed HIV-1 latency in cell line based latency models, in two ex vivo infected primary cell models of latency, as well as in HIV-1 infected patient's CD4. + T cells, without inducing T cell proliferation or activation. BAFi-induced HIV-1 latency reversal was synergistically enhanced upon PKC pathway activation and HDAC-inhibition. Therefore BAFi's constitute a promising family of molecules for inclusion in therapeutic combinatorial HIV-1 latency reversal.

Published
2016
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39. HIV: Treatment and Comorbidity

Author

Rokx, C. (Casper) and Rokx, C. (Casper)

Abstract

Clinicians worldwide strive to improve HIV care for their patients. Antiretroviral therapy prevents HIV related mortality and is lifelong. A clinical evaluation of these treatment strategies is necessary to identify strategies that may jeopardize treatment effectiveness and patient safety. The first part of this thesis concerns the relative efficacy of treatment with either lamivudine or emtricitabine combined with tenofovir disoproxil-fumarate as nucleoside reverse transcriptase inhibitor backbone. The use of lamivudine is associated with more virological failure in certain treatment regimens for viremic HIV patients. Antiretroviral drug switches are addressed next. We evaluate three potential high-risk antiretroviral switches due to cytochrome P450 interactions, acquired resistance and dolutegravir monotherapy in aviremic HIV patients. The patients’ safety seems ensured by these switch strategies. HIV maintenance therapy with single tablets containing multiple drugs or drug monotherapy is possible in various clinical situations, including resistance and comorbidities. Third, we show that exposure to inhibitors of the renal multidrug resistance protein transporter is associated with renal dysfunction in patients treated with tenofovir disoproxil-fumarate. Cardiovascular risks are comparable regardless of rilpivirine or nevirapine treatment and HIV related Kaposi sarcoma or multicentric Castleman’s disease are effectively treated with peginterferon or rituximab. In the last part, we explore

Published
2016

40. Virological responses to lamivudine or emtricitabine when combined with tenofovir and a protease inhibitor in treatment-naïve HIV-1-infected patients in the Dutch AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort

Author

Epidemiology & Health Economics, MMB, MS Infectieziekten, Circulatory Health, Infection & Immunity, MS Interne Geneeskunde, Directie Raad van Bestuur, MMB Medische Staf, Infectieziekten patientenzorg, Other research (not in main researchprogram), Onderwijssecretariaat, Divisieleiding O&O, Child Health, CTI Bont, Infectieziekten onderzoek1 (Bont), Rokx, C., Gras, L., van de Vijver, D. A M C, Verbon, A., Rijnders, B. J A, Prins, J. M., Kuijpers, T. W., Scherpbier, H. J., van der Meer, J. T M, Wit, F. W M N, Godfried, M. H., Reiss, P., van der Poll, T., Nellen, F. J B, Lange, J. M A, Geerlings, S. E., van Vugt, M., Pajkrt, D., Bos, J. C., van der Valk, M, Wiersinga, W. J., Goorhuis, A., Hovius, J. W R, Lowe, S., Oude Lashof, A., Posthouwer, D., Pronk, M. J H, Ammerlaan, H. S M, van der Ende, M. E., de Vries-Sluijs, T. E M S, Schurink, C. A M, Nouwen, J. L., van Gorp, E. C M, van der Feltz, M., Driessen, G. J A, van Rossum, A. M C, Branger, J., Schippers, E. F., van Nieuwkoop, C., van Elzakker, E. P., Groeneveld, P. H P, Bouwhuis, J. W., Soetekouw, R., ten Kate, R. W., Kroon, F. P., van Dissel, J. T., Arend, S. M., de Boer, M. G J, Jolink, H., Vollaard, A. M., Bauer, M. P., den Hollander, J. G., Pogany, K., van Twillert, G., Kortmann, W., Cohen Stuart, J. W T, Diederen, B. M W, Leyten, E. M S, Gelinck, L. B S, Kootstra, G. J., Delsing, C. E., Brinkman, K., Blok, W. L., Frissen, P. H J, Schouten, W. E M, van den Berk, G. E L, van Kasteren, M. E E, Brouwer, A.E., Veenstra, J., Lettinga, K. D., Mulder, J. W., Vrouenraets, S. M E, Lauw, F. N., van Eeden, A., Verhagen, D. W M, Sprenger, H. G., Scholvinck, E. H., van Assen, S., Bierman, W. F W, Wilting, K. R., Stienstra, Y., Koopmans, P. P., Keuter, M., van der Ven, A. J A M, ter Hofstede, H. J M, Dofferhoff, A. S M, Warris, A., van Crevel, R., Hoepelman, A. I M, Mudrikova, T., Schneider, M. M E, Ellerbroek, P. M., Oosterheert, J. J., Arends, J. E., Wassenberg, M. W M, Barth, R. E., van Agtmael, M. A., Perenboom, R. M., Claessen, F. A P, Bomers, M., Peters, E.J.G., Geelen, S. P M, Wolfs, T. F W, Bont, L. J., Richter, C., van der Berg, J. P., Gisolf, E. H., van den Berge, M., Stegeman, A., van Vonderen, M. G A, van Houte, D. P F, Weijer, S., el Moussaoui, R., Winkel, C., Muskiet, F., Durand, A., Voigt, R., Epidemiology & Health Economics, MMB, MS Infectieziekten, Circulatory Health, Infection & Immunity, MS Interne Geneeskunde, Directie Raad van Bestuur, MMB Medische Staf, Infectieziekten patientenzorg, Other research (not in main researchprogram), Onderwijssecretariaat, Divisieleiding O&O, Child Health, CTI Bont, Infectieziekten onderzoek1 (Bont), Rokx, C., Gras, L., van de Vijver, D. A M C, Verbon, A., Rijnders, B. J A, Prins, J. M., Kuijpers, T. W., Scherpbier, H. J., van der Meer, J. T M, Wit, F. W M N, Godfried, M. H., Reiss, P., van der Poll, T., Nellen, F. J B, Lange, J. M A, Geerlings, S. E., van Vugt, M., Pajkrt, D., Bos, J. C., van der Valk, M, Wiersinga, W. J., Goorhuis, A., Hovius, J. W R, Lowe, S., Oude Lashof, A., Posthouwer, D., Pronk, M. J H, Ammerlaan, H. S M, van der Ende, M. E., de Vries-Sluijs, T. E M S, Schurink, C. A M, Nouwen, J. L., van Gorp, E. C M, van der Feltz, M., Driessen, G. J A, van Rossum, A. M C, Branger, J., Schippers, E. F., van Nieuwkoop, C., van Elzakker, E. P., Groeneveld, P. H P, Bouwhuis, J. W., Soetekouw, R., ten Kate, R. W., Kroon, F. P., van Dissel, J. T., Arend, S. M., de Boer, M. G J, Jolink, H., Vollaard, A. M., Bauer, M. P., den Hollander, J. G., Pogany, K., van Twillert, G., Kortmann, W., Cohen Stuart, J. W T, Diederen, B. M W, Leyten, E. M S, Gelinck, L. B S, Kootstra, G. J., Delsing, C. E., Brinkman, K., Blok, W. L., Frissen, P. H J, Schouten, W. E M, van den Berk, G. E L, van Kasteren, M. E E, Brouwer, A.E., Veenstra, J., Lettinga, K. D., Mulder, J. W., Vrouenraets, S. M E, Lauw, F. N., van Eeden, A., Verhagen, D. W M, Sprenger, H. G., Scholvinck, E. H., van Assen, S., Bierman, W. F W, Wilting, K. R., Stienstra, Y., Koopmans, P. P., Keuter, M., van der Ven, A. J A M, ter Hofstede, H. J M, Dofferhoff, A. S M, Warris, A., van Crevel, R., Hoepelman, A. I M, Mudrikova, T., Schneider, M. M E, Ellerbroek, P. M., Oosterheert, J. J., Arends, J. E., Wassenberg, M. W M, Barth, R. E., van Agtmael, M. A., Perenboom, R. M., Claessen, F. A P, Bomers, M., Peters, E.J.G., Geelen, S. P M, Wolfs, T. F W, Bont, L. J., Richter, C., van der Berg, J. P., Gisolf, E. H., van den Berge, M., Stegeman, A., van Vonderen, M. G A, van Houte, D. P F, Weijer, S., el Moussaoui, R., Winkel, C., Muskiet, F., Durand, A., and Voigt, R.

Published
2016

44. Partner notification for reduction of HIV-1 transmission and related costs among men who have sex with men: A mathematical modeling study

Author

Nichols, B.E. (Brooke), Götz, H.M. (Hannelore), Gorp, E.C.M. (Eric) van, Verbon, A. (Annelies), Rokx, C. (Casper), Boucher, C.A.B. (Charles), Vijver, D.A.M.C. (David) van de, Nichols, B.E. (Brooke), Götz, H.M. (Hannelore), Gorp, E.C.M. (Eric) van, Verbon, A. (Annelies), Rokx, C. (Casper), Boucher, C.A.B. (Charles), and Vijver, D.A.M.C. (David) van de

Abstract

Background Earlier antiretroviral treatment initiation prevents new HIV infections. A key problem in HIV prevention and care is the high number of patients diagnosed late, as these undiagnosed patients can continue forward HIV transmission. We modeled the impact on the Dutch menwho-have-sex-with-men (MSM) HIV epidemic and cost-effectiveness of an existing partner notification process for earlier identification of HIV-infected individuals to reduce HIV transmission. Methods Reduction in new infections and cost-effectiveness ratios were obtained for the use of partner notification to identify 5% of all new diagnoses (Scenario 1) and 20% of all new diagnoses (Scenario 2), versus no partner notification. Costs and quality adjusted life years (QALYs) were assigned to each disease state and calculated over 5 year increments for a20 year period. Results Partner notification is predicted to avert 18-69 infections (interquartile range [IQR] 13-24; 51-93) over the course of 5 years countrywide to 221-830 (IQR 140-299; 530-1,127) over 20 years for Scenario 1 and 2 respectively. Partner notification was considered cost-effective in t

Published
2015
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45. The efficacy, pharmacokinetics, safety and cardiovascular risks of switching nevirapine to rilpivirine in HIV-1 patients: the RPV switch study

Author

Rokx, C., Blonk, M., Verbon, A., Burger, D.M., Rijnders, B.J., Rokx, C., Blonk, M., Verbon, A., Burger, D.M., and Rijnders, B.J.

Abstract

Contains fulltext : 136114.pdf (publisher's version ) (Open Access), INTRODUCTION: Nevirapine (NVP) induces cytochrome P450 3A4 by which rilpivirine (RPV) is metabolized. Switching NVP to RPV could result in decreased RPV exposure with subsequent virological failure and dyslipidemia because NVP is regarded as the least dyslipidemic, non-nucleoside, reverse transcriptase inhibitor. This trial evaluated the efficacy, pharmacokinetics, safety and cardiovascular risks of switching NVP to RPV. MATERIALS AND METHODS: Prospective open label controlled trial. HIV-1 patients with HIV-1 RNA <50 copies/mL on once daily NVP, emtricitabine/tenofovir (FTC/TDF) switched to single tablet RPV/FTC/TDF. Eligible patients on NVP, FTC/TDF were controls. Primary endpoint was week 12 HIV-1 RNA <50 copies/mL by intention to treat analysis. Secondary endpoints were week 24 HIV-1 RNA <50 copies/mL, NVP and RPV pharmacokinetics, safety and fasting lipids, Framingham risk scores (FRS) and Adult Treatment Panel III (ATP-III) lipid goals. RESULTS: Of 189 eligible patients, we included 50 RPV switchers and 139 NVP controls. Week 12 HIV-RNA was <50 copies/mL in 46/50 switchers (92.0%) which was not different from the hypothesized 90% week 12 suppression rate (p=.431). Forty-four of 50 switchers had week 24 HIV-1 RNA <50 copies/mL compared to 126/139 controls (difference: 2.6%, 95% CI -7.6% to 12.8%, p=.593). NVP plasma concentrations were below detection level in all at week 3. Mean week 1 RPV trough concentration was 0.083 mg/L and comparable to phase III trial data (p=0.747). Adverse events occurred in 36 switchers, the majority (82.0%) were grade one. Two switchers discontinued RPV for side effects. Significant changes over 24 weeks (p<0.001) were observed in switchers on total cholesterol (TC, -0.67 mmol/L, 95% CI -0.50 to 0.83), low density lipoprotein (LDL)-C (-0.36, 95% CI -0.21 to -0.51) and high density lipoprotein (HDL)-C (-0.28, 95% CI -0.20 to -0.35). The TC/HDL-C ratio increased 0.20 (95% CI 0.02 to 0.37; p=.029) and systolic blood pressure decreased 6

Published
2014

46. National medical specialty guidelines of HIV indicator conditions in Europe lack adequate HIV testing recommendations: a systematic guideline review

Author

Jordans, Carlijn C.E., Vasylyev, Marta, Rae, Caroline, Jakobsen, Marie Louise, Vassilenko, Anna, Dauby, Nicolas, Grevsen, Anne Louise, Jakobsen, Stine Finne, Raahauge, Anne, Champenois, Karen, Papot, Emmanuelle, Malin, Jakob J., Boender, T. Sonia, Behrens, Georg M.N., Gruell, Henning, Neumann, Anja, Spinner, Christoph D., Valbert, Frederik, Akinosoglou, Karolina, Kostaki, Evangelia G., Nozza, Silvia, Giacomelli, Andrea, Lapadula, Giuseppe, Mazzitelli, Maria, Torti, Carlo, Matulionyte, Raimonda, Matulyte, Elzbieta, Van Welzen, Berend J., Hensley, Kathryn S., Thompson, Magdalena, Ankiersztejn-Bartczak, Magdalena, Skrzat-Klapaczyńska, Agata, Sǎndulescu, Oana, Streinu-Cercel, Adrian, Streinu-Cercel, Anca, Miron, Viktor Daniel, Pokrovskaya, Anastasia, Hachfeld, Anna, Dorokhina, Antonina, Sukach, Maryna, Lord, Emily, Sullivan, Ann K., Rokx, Casper, Medical Microbiology & Infectious Diseases, Jordans, C, Vasylyev, M, Rae, C, Jakobsen, M, Vassilenko, A, Dauby, N, Grevsen, A, Jakobsen, S, Raahauge, A, Champenois, K, Papot, E, Malin, J, Boender, T, Behrens, G, Gruell, H, Neumann, A, Spinner, C, Valbert, F, Akinosoglou, K, Kostaki, E, Nozza, S, Giacomelli, A, Lapadula, G, Mazzitelli, M, Torti, C, Matulionyte, R, Matulyte, E, Van Welzen, B, Hensley, K, Thompson, M, Ankiersztejn-Bartczak, M, Skrzat-Klapaczyńska, A, Săndulescu, O, Streinu-Cercel, A, Miron, V, Pokrovskaya, A, Hachfeld, A, Dorokhina, A, Sukach, M, Lord, E, Sullivan, A, and Rokx, C

Subjects
Europe, SDG 3 - Good Health and Well-being, Epidemiology, HIV, indicator conditions, AIDS-defining condition, Virology, Public Health, Environmental and Occupational Health, Medizin, guidelines, Wirtschaftswissenschaften, 610 Medizin und Gesundheit
Abstract

Background Adequate identification and testing of people at risk for HIV is fundamental for the HIV care continuum. A key strategy to improve timely testing is HIV indicator condition (IC) guided testing. Aim To evaluate the uptake of HIV testing recommendations in HIV IC-specific guidelines in European countries. Methods Between 2019 and 2021, European HIV experts reviewed guideline databases to identify all national guidelines of 62 HIV ICs. The proportion of HIV IC guidelines recommending HIV testing was reported, stratified by subgroup (HIV IC, country, eastern/western Europe, achievement of 90–90–90 goals and medical specialty). Results Of 30 invited European countries, 15 participated. A total of 791 HIV IC guidelines were identified: median 47 (IQR: 38–68) per country. Association with HIV was reported in 69% (545/791) of the guidelines, and 46% (366/791) recommended HIV testing, while 42% (101/242) of the AIDS-defining conditions recommended HIV testing. HIV testing recommendations were observed more frequently in guidelines in eastern (53%) than western (42%) European countries and in countries yet to achieve the 90–90–90 goals (52%) compared to those that had (38%). The medical specialties internal medicine, neurology/neurosurgery, ophthalmology, pulmonology and gynaecology/obstetrics had an HIV testing recommendation uptake below the 46% average. None of the 62 HIV ICs, countries or medical specialties had 100% accurate testing recommendation coverage in all their available HIV IC guidelines. Conclusion Fewer than half the HIV IC guidelines recommended HIV testing. This signals an insufficient adoption of this recommendation in non-HIV specialty guidelines across Europe.

Published
2022

47. Development of C-TILDA: A modified TILDA method for reservoir quantification in long term treated patients infected with subtype C HIV-1

Author

Vanessa D'Urbano, Tokameh Mahmoudi, Isabella Bon, Maria Carla Re, Charles A. Boucher, Annelies Verbon, Jeroen J. A. van Kampen, Casper Rokx, Elisa De Crignis, Alessia Bertoldi, Giorgio Gallinella, Rob A. Gruters, Leonardo Calza, Internal Medicine, Medical Microbiology & Infectious Diseases, Virology, Biochemistry, Bertoldi A., D'Urbano V., Bon I., Verbon A., Rokx C., Boucher C., van Kampen J.J.A., Gruters R.A., Gallinella G., Calza L., Mahmoudi T., De Crignis E., and Re M.C.

Subjects
0301 basic medicine, CD4-Positive T-Lymphocytes, Serial dilution, Sustained Virologic Response, 030106 microbiology, Human immunodeficiency virus (HIV), CD4-CD8 Ratio, HIV Infections, Biology, medicine.disease_cause, Antiviral Agents, Sensitivity and Specificity, Virus, HIV Testing, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Virology, HIV subtype C, medicine, Humans, Cell stimulation, Gene, Messenger RNA, Hiv epidemiology, HIV, Viral Load, Virus Latency, 030104 developmental biology, Reservoir quantification, DNA, Viral, HIV-1, TILDA, CD8
Abstract

A better characterization of the HIV reservoir is pivotal for the development of effective eradication strategies. Accurate quantification of the latent reservoir remains challenging. Starting from a regular blood draw, the Tat/Rev induced limiting dilution assay (TILDA) combines serial dilution of CD4+ T cells with a PCR-based detection of HIV-1 spliced mRNA produced upon cell stimulation. Here we adapted the original protocol for HIV-1 subtype B to detect tat/rev mRNAs transcribed from reactivated latently infected cells in long term suppressed patients infected with HIV-1 subtype C. Given the heterogeneity of global HIV epidemiology, it is pivotal to develop assays with optimal performances also in patients infected with non-B subtypes. We observed that, in these patients infected with subtype C virus, the HIV reservoir quantified by TILDA correlates with both the time of virological suppression and CD4/CD8 ratio.

Published
2019

48. Oral HIV pre-exposure prophylaxis use and resistance-associated mutations among men who have sex with men and transgender persons newly diagnosed with HIV in the Netherlands: results from the ATHENA cohort, 2018 to 2022.

Author

Jongen VW, Bezemer D, van Sighem A, Boyd A, Rokx C, Grintjes K, Cents-Bosma A, Op de Coul E, van Benthem B, Wensing A, Wit FW, and van der Valk M

Subjects
Humans, Male, Netherlands epidemiology, Adult, HIV-1 genetics, HIV-1 isolation & purification, Middle Aged, Cohort Studies, Female, Pre-Exposure Prophylaxis statistics & numerical data, HIV Infections prevention & control, HIV Infections epidemiology, Homosexuality, Male statistics & numerical data, Anti-HIV Agents therapeutic use, Anti-HIV Agents administration & dosage, Mutation, Drug Resistance, Viral genetics, Transgender Persons statistics & numerical data
Abstract

BackgroundIn the Netherlands, HIV pre-exposure prophylaxis (PrEP) has been available since 2019. However, the extent of PrEP use prior to HIV diagnosis and development of PrEP-resistance-associated mutations (RAMs) is not known.AimWe assessed prior PrEP use and potential transmission of PrEP RAMs among men who have sex with men (MSM) and transgender persons (TGP) with a new HIV diagnosis in the Netherlands.MethodsData on prior PrEP use between 1 January 2018 and 31 December 2022 were available from the Dutch national ATHENA cohort. We assessed proportion of prior PrEP use, detected PrEP associated RAMs and assessed potential onward transmission of RAMs between 2010 and 2022 using a maximum likelihood tree.ResultsData on prior PrEP use were available for 583/1,552 (36.3%) individuals, with 16% (94/583) reporting prior PrEP use. In 489 individuals reporting no prior PrEP use, 51.5% did not use PrEP due to: low HIV-risk perception (29%), no access (19.1%), personal preference (13.1%), and being unaware of PrEP (19.1%). For PrEP users, 13/94 (13.8%) harboured a M184V/I mutation, of whom two also harboured a K65R mutation. In people with a recent HIV infection, detection of PrEP RAMs increased from 0.23% (2/862) before 2019 to 4.11% (9/219) from 2019. We found no evidence of onward transmission of PrEP RAMs.ConclusionThe prevalence of PrEP-associated RAMs has increased since PrEP became available in the Netherlands. More widespread access to PrEP and retaining people in PrEP programmes when still at substantial risk is crucial to preventing new HIV infections.

Published
2024
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49. Author Correction: Prospective individual patient data meta-analysis of two randomized trials on convalescent plasma for COVID-19 outpatients.

Author

Millat-Martinez P, Gharbharan A, Alemany A, Rokx C, Geurtsvankessel C, Papageorgiou G, van Geloven N, Jordans C, Groeneveld G, Swaneveld F, van der Schoot E, Corbacho-Monné M, Ouchi D, Piccolo Ferreira F, Malchair P, Videla S, García García V, Ruiz-Comellas A, Ramírez-Morros A, Rodriguez Codina J, Amado Simon R, Grifols JR, Blanco J, Blanco I, Ara J, Bassat Q, Clotet B, Baro B, Troxel A, Zwaginga JJ, Mitjà O, and Rijnders BJA

Published
2024
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50. Dolutegravir/Lamivudine Is Noninferior to Continuing Dolutegravir- and Non-Dolutegravir-Based Triple-Drug Antiretroviral Therapy in Virologically Suppressed People With Human Immunodeficiency Virus: DUALING Prospective Nationwide Matched Cohort Study.

Author

Vasylyev M, Wit FWNM, Jordans CCE, Soetekouw R, van Lelyveld SFL, Kootstra GJ, Delsing CE, Ammerlaan HSM, van Kasteren MEE, Brouwer AE, Leyten EMS, Claassen MAA, Hassing RJ, den Hollander JG, van den Berge M, Roukens AHE, Bierman WFW, Groeneveld PHP, Lowe SH, van Welzen BJ, Richel O, Nellen JF, van den Berk GEL, van der Valk M, Rijnders BJA, and Rokx C

Abstract

Background: Confirming the efficacy of dolutegravir/lamivudine in clinical practice solidifies recommendations on its use., Methods: Prospective cohort study (DUALING) in 24 human immunodeficiency virus (HIV) treatment centers in the Netherlands. HIV RNA-suppressed cases were on triple-drug antiretroviral regimens without prior virological failure or resistance and started dolutegravir/lamivudine. Cases were 1:2 matched to controls on triple-drug antiretroviral regimens by the use of dolutegravir-based regimens, age, sex, transmission route, CD4 + T-cell nadir, and HIV RNA zenith. The primary endpoint was the treatment failure rate in cases versus controls at 1 year by intention-to-treat and on-treatment analyses with 5% noninferiority margin., Results: The 2040 participants were 680 cases and 1380 controls. Treatment failure in the 390 dolutegravir-based cases versus controls occurred in 8.72% and 12.50% (difference: -3.78% [95% confidence interval {CI}, -7.49% to .08%]) by intention-to-treat and 1.39% and 0.80% (difference: 0.59% [95% CI, -.80% to 1.98%]) by on-treatment analyses. The treatment failure risk in 290 non-dolutegravir-based cases was also noninferior to controls. Antiretroviral regimen modifications unrelated to virological failure explained the higher treatment failure rate by intention-to-treat. A shorter time on triple-drug antiretroviral therapy and being of non-Western origin was associated with treatment failure. Treatment failure, defined as 2 consecutive HIV RNA >50 copies/mL, occurred in 4 cases and 5 controls but without genotypic resistance detected. Viral blips occured comparable in cases and controls but cases gained more weight, especially when tenofovir-based regimens were discontinued., Conclusions: In routine care, dolutegravir/lamivudine was noninferior to continuing triple-drug antiretroviral regimens after 1 year, supporting the use of dolutegravir/lamivudine in clinical practice., Clinical Trials Registration: NCT04707326., Competing Interests: Potential conflicts of interest. F. W. N. M. W. reports consulting fees from ViiV Healthcare. C. R. reports research grants, travel reimbursement, and compensation for participation in scientific boards from ViiV Healthcare and Gilead Sciences. B. J. A. R. reports consulting fees from ViiV Healthcare, Gilead Sciences, and MSD and compensation for educational activities from ViiV Healthcare. M. v. d. V. reports research grants and consulting fees from Gilead Sciences, ViiV Healthcare, and MSD, all paid to his institution. C. C. E. J. reports travel reimbursement from Gilead Sciences and compensation for presentation from ViiV Healthcare. S. v. L. reports a research grant from Pfizer outside the context of this study. J. G. d. H. reports compensation for participation in scientific boards from ViiV Healthcare, Gilead Sciences, Moderna, and GSK. B. J. v. W. reports a research grant from Gilead Sciences, consulting fees from ViiV Healthcare and Gilead Sciences, compensation for participation on a data and safety monitoring board from ViiV Healthcare and Gilead Sciences, and payment for lectures from Gilead Sciences. J. F. N. reports compensation for educational activities and participation in scientific advisory boards from Gilead Sciences, ViiV Healthcare, and MSD, all paid to her institution. All other authors report no potential conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Published
2024
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