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1. Access to menstrual hygiene products through incentivised, community-based, peer-led sexual and reproductive health services before and during the COVID-19 pandemic: findings from the Yathu Yathu trial

Author

Hensen B, Gondwe M, Phiri M, Schaap A, Simuyaba M, Floyd S, Mwenge L, Sigande L, Shanaube K, Simwinga M, Fidler S, Hayes R, and Ayles H

Subjects
Public aspects of medicine, RA1-1270
Abstract

Abstract Background Access to affordable and effective menstrual hygiene products (MHP) is critical to the menstrual health of adolescent girls and young women (AGYW). In this mixed-methods analysis, we use data from a programme delivering comprehensive sexual and reproductive health (SRH) services to describe access to MHP and how COVID-19-related closures affected access to MHP; we use qualitative data to understand AGYW’s experience accessing products during the study. Methods Between September 2019-January 2021, we used data routinely collected from ten Yathu Yathu hubs offering community-based, peer-led SRH services to adolescents and young people aged 15–24. Hubs offered free MHP (primarily disposable pads) as a service. To incentivise service access, a “loyalty” card system was embedded within Yathu Yathu, allowing individuals to gain points for services accessed and redeem rewards using these points. Branded pads, tampons and reusable pads were among available rewards. We describe access to service pads and to reward MHP, and use logistic regression to investigate factors associated with accessing pads and reward products before (Sept 2019-March 2020) and after (July 2020-Jan 2021) COVID-19-related closures. Focus group discussions explored accessibility of offering MHP through hubs. Results Between September 2019-January 2021, 6374 AGYW made 34,116 hub visits to access an SRH service and/or redeem a reward. At 30% of these visits, AGYW accessed any MHP. Before COVID19-closures, an average of 17% of monthly visits were for freely-available disposable pads compared to 34% after hubs reopened (p

Published
2022
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2. Achieving the UNAIDS 90-90-90 targets: a comparative analysis of four large community randomised trials delivering universal testing and treatment to reduce HIV transmission in sub-Saharan Africa.

Author

Sabapathy, K, Balzer, L, Larmarange, J, Block, L, Floyd, S, Iwuji, C, Wirth, K, Ayles, H, Fidler, S, Kamya, M, Petersen, M, Havlir, D, Dabis, F, Moore, J, and Hayes, R

Subjects
Humans, HIV Infections, Adult, South Africa, Zambia, Randomized Controlled Trials as Topic, Epidemics, HIV Testing, Antiretroviral treatment, HIV, Treatment as Prevention, UNAIDS 90-90-90, Universal Testing and Treatment, Clinical Research, Clinical Trials and Supportive Activities, Mental Health, HIV/AIDS, Infectious Diseases, Prevention, Infection, Good Health and Well Being, Public Health and Health Services, Public Health
Abstract

BackgroundFour large community-randomized trials examining universal testing and treatment (UTT) to reduce HIV transmission were conducted between 2012-2018 in Botswana, Kenya, Uganda, Zambia and South Africa. In 2014, the UNAIDS 90-90-90 targets were adopted as a useful metric to monitor coverage. We systematically review the approaches used by the trials to measure intervention delivery, and estimate coverage against the 90-90-90 targets. We aim to provide in-depth understanding of the background contexts and complexities that affect estimation of population-level coverage related to the 90-90-90 targets.MethodsEstimates were based predominantly on "process" data obtained during delivery of the interventions which included a combination of home-based and community-based services. Cascade coverage data included routine electronic health records, self-reported data, survey data, and active ascertainment of HIV viral load measurements in the field.ResultsThe estimated total adult populations of trial intervention communities included in this study ranged from 4,290 (TasP) to 142,250 (Zambian PopART Arm-B). The estimated total numbers of PLHIV ranged from 1,283 (TasP) to 20,541 (Zambian PopART Arm-B). By the end of intervention delivery, the first-90 target (knowledge of HIV status among all PLHIV) was met by all the trials (89.2%-94.0%). Three of the four trials also achieved the second- and third-90 targets, and viral suppression in BCPP and SEARCH exceeded the UNAIDS target of 73%, while viral suppression in the Zambian PopART Arm-A and B communities was within a small margin (~ 3%) of the target.ConclusionsAll four UTT trials aimed to implement wide-scale testing and treatment for HIV prevention at population level and showed substantial increases in testing and treatment for HIV in the intervention communities. This study has not uncovered any one estimation approach which is superior, rather that several approaches are available and researchers or policy makers seeking to measure coverage should reflect on background contexts and complexities that affect estimation of population-level coverage in their specific settings. All four trials surpassed UNAIDS targets for universal testing in their intervention communities ahead of the 2020 milestone. All but one of the trials also achieved the 90-90 targets for treatment and viral suppression. UTT is a realistic option to achieve 95-95-95 by 2030 and fast-track the end of the HIV epidemic.

Published
2022

5. Incidence of self-reported tuberculosis treatment with community-wide universal testing and treatment for HIV and tuberculosis screening in Zambia and South Africa: A planned analysis of the HPTN 071 (PopART) cluster-randomised trial

Author

Telisinghe, L., Floyd, S., MacLeod, D., Schaap, A., Dunbar, R., Bwalya, J., Bell-Mandla, N., Piwowar-Manning, E., Donnell, D., Shaunaube, K., Bock, P., Fidler, S., Hayes, R. J., and Ayles, H. M.

Subjects
South Africa -- Health aspects, Zambia -- Health aspects, HIV (Viruses) -- Care and treatment -- Diagnosis -- Control, Medical research, Medicine, Experimental, Tuberculosis -- Care and treatment -- Diagnosis -- Control, Medical screening -- Methods, Biological sciences
Abstract

Background HIV is a potent risk factor for tuberculosis (TB). Therefore, community-wide universal testing and treatment for HIV (UTT) could contribute to TB control, but evidence for this is limited. Community-wide TB screening can decrease population-level TB prevalence. Combining UTT with TB screening could therefore significantly impact TB control in sub-Saharan Africa, but to our knowledge there is no evidence for this combined approach. Methods and findings HPTN 071 (PopART) was a community-randomised trial conducted between November 2013 to July 2018; 21 Zambian and South African communities (with a total population of approximately 1 million individuals) were randomised to arms A (community-wide UTT and TB screening), B (community-wide universal HIV testing with treatment following national guidelines and TB screening), or C (standard-of-care). In a cohort of randomly selected adults (18 to 44 years) enrolled between 2013 and 2015 from all 21 communities (total size 38,474; 27,139 [71%] female; 8,004 [21%] HIV positive) and followed-up annually for 36 months to measure the population-level impact of the interventions, data on self-reported TB treatment in the previous 12 months (self-reported TB) were collected by trained research assistants and recorded using a structured questionnaire at each study visit. In this prespecified analysis of the trial, self-reported TB incidence rates were measured by calendar year between 2014 and 2017/2018. A p-value [less than or equal to]0.05 on hypothesis testing was defined as reaching statistical significance. Between January 2014 and July 2018, 38,287 individuals were followed-up: 494 self-reported TB during 104,877 person-years. Overall incidence rates were similar across all arms in 2014 and 2015 (0.33 to 0.46/100 person-years). In 2016 incidence rates were lower in arm A compared to C overall (adjusted rate ratio [aRR] 0.48 [95% confidence interval (95% CI) 0.28 to 0.81; p = 0.01]), with statistical significance reached. In 2017/2018, while incidence rates were lower in arm A compared to C, statistical significance was not reached (aRR 0.58 [95% CI 0.27 to 1.22; p = 0.13]). Among people living with HIV (PLHIV) incidence rates were lower in arm A compared to C in 2016 (RR 0.56 [95% CI 0.29 to 1.08; p = 0.08]) and 2017/2018 (RR 0.50 [95% CI 0.26 to 0.95; p = 0.04]); statistical significance was only reached in 2017/2018. Incidence rates in arms B and C were similar, overall and among PLHIV. Among HIV-negative individuals, there were too few events for cross-arm comparisons. Study limitations include the use of self-report which may have been subject to under-reporting, limited covariate adjustment due to the small number of events, and high losses to follow-up over time. Conclusions In this study, community-wide UTT and TB screening resulted in substantially lower TB incidence among PLHIV at population-level, compared to standard-of-care, with statistical significance reached in the final study year. There was also some evidence this translated to a decrease in self-reported TB incidence overall in the population. Reduction in arm A but not B suggests UTT drove the observed effect. Our data support the role of UTT in TB control, in addition to HIV control, in high TB/HIV burden settings. Trial registration ClinicalTrials.gov: NCT01900977., Author(s): L. Telisinghe 1,2,*, S. Floyd 3, D. MacLeod 3, A. Schaap 2,3, R. Dunbar 4, J. Bwalya 2, N. Bell-Mandla 4, E. Piwowar-Manning 5, D. Donnell 6, K. Shaunaube [...]

Published
2024
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13. PCR134 associations between HIV stigma and health-related quality of life among people living with HIV in Zambia and South Africa: a cross-sectional analysis of data from the HPTN 071 (POPART) study

Author

Hall, E, Davis, K, Ohrnberger, J, Gregson, S, Thomas, R, Hargreaves, J, Pliakas, T, Bwalya, J, Dunbar, R, Mainga, T, Shanaube, K, Hoddinott, G, Bond, V, Bock, P, Ayles, H, Stangl, A, Donnell, D, Hayes, R, Fidler, S, and Hauck, K

Abstract

Little is known about the relationship between HIV stigma and health-related quality of life (HRQoL) among people living with HIV (PLHIV). We aimed to explore associations between four HIV stigma outcomes and HRQoL among PLHIV and examined which HRQoL domains were most affected.

Published
2023

14. OP 1.9 – 00042 Measuring the impact of early 3BNC117 intervention at ART initiation on the productive reservoir in a cohort of diverse viral subtypes: results from the VIP-SPOT assay in the eCLEAR trial

Author

Puertas, M.C., primary, Gunst, J.D., additional, Pahus, M.H., additional, Kinloch, N.N., additional, Copertino, D.C., additional, Ward, Adam R., additional, Brumme, Z.L., additional, Jones, R. Brad, additional, Tolstrup, M., additional, Fidler, S., additional, Søgaard, O.S., additional, and Martinez-Picado, J., additional

Published
2022
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16. Achieving the UNAIDS 90-90-90 targets: a comparative analysis of four large community randomised trials delivering universal testing and treatment to reduce HIV transmission in sub-Saharan Africa

Author

Sabapathy, K., Balzer, L., Larmarange, Joseph, Block, L., Floyd, S., Iwuji, C., Wirth, K., Ayles, H., Fidler, S., Kamya, M., Petersen, M., Havlir, D., Dabis, F., Moore, J., Hayes, R., London School of Hygiene and Tropical Medicine (LSHTM), University of California [Berkeley] (UC Berkeley), University of California (UC), Centre population et développement (CEPED - UMR_D 196), Institut de Recherche pour le Développement (IRD)-Université Paris Cité (UPCité), Centers for Disease Control and Prevention [Atlanta] (CDC), Centers for Disease Control and Prevention, Peraton Labs, Brighton and Sussex Medical School (BSMS), Africa Health Research Institute [Durban/Mtubatuba] (AHRI), Harvard School of Public Health, Zambart, Imperial College London, Makerere University [Kampala, Ouganda] (MAK), Infectious Diseases Research Collaboration [Kampala, Ouganda], University of California [San Francisco] (UC San Francisco), Université de Bordeaux (UB), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Global Health in the Global South (GHiGS), Institut de Recherche pour le Développement (IRD)- Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Adult, Clinical Trials and Supportive Activities, UNAIDS 90-90-90, Zambia, HIV Infections, HIV Testing, South Africa, Clinical Research, Humans, Treatment as Prevention, Epidemics, Randomized Controlled Trials as Topic, Prevention, Public Health, Environmental and Occupational Health, HIV, Universal Testing and Treatment, Antiretroviral treatment, Mental Health, Infectious Diseases, Good Health and Well Being, Public Health and Health Services, HIV/AIDS, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Public Health, Infection
Abstract

Background Four large community-randomized trials examining universal testing and treatment (UTT) to reduce HIV transmission were conducted between 2012–2018 in Botswana, Kenya, Uganda, Zambia and South Africa. In 2014, the UNAIDS 90–90-90 targets were adopted as a useful metric to monitor coverage. We systematically review the approaches used by the trials to measure intervention delivery, and estimate coverage against the 90–90-90 targets. We aim to provide in-depth understanding of the background contexts and complexities that affect estimation of population-level coverage related to the 90–90-90 targets. Methods Estimates were based predominantly on “process” data obtained during delivery of the interventions which included a combination of home-based and community-based services. Cascade coverage data included routine electronic health records, self-reported data, survey data, and active ascertainment of HIV viral load measurements in the field. Results The estimated total adult populations of trial intervention communities included in this study ranged from 4,290 (TasP) to 142,250 (Zambian PopART Arm-B). The estimated total numbers of PLHIV ranged from 1,283 (TasP) to 20,541 (Zambian PopART Arm-B). By the end of intervention delivery, the first-90 target (knowledge of HIV status among all PLHIV) was met by all the trials (89.2%-94.0%). Three of the four trials also achieved the second- and third-90 targets, and viral suppression in BCPP and SEARCH exceeded the UNAIDS target of 73%, while viral suppression in the Zambian PopART Arm-A and B communities was within a small margin (~ 3%) of the target. Conclusions All four UTT trials aimed to implement wide-scale testing and treatment for HIV prevention at population level and showed substantial increases in testing and treatment for HIV in the intervention communities. This study has not uncovered any one estimation approach which is superior, rather that several approaches are available and researchers or policy makers seeking to measure coverage should reflect on background contexts and complexities that affect estimation of population-level coverage in their specific settings. All four trials surpassed UNAIDS targets for universal testing in their intervention communities ahead of the 2020 milestone. All but one of the trials also achieved the 90–90 targets for treatment and viral suppression. UTT is a realistic option to achieve 95–95-95 by 2030 and fast-track the end of the HIV epidemic.

Published
2022
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19. Booster vaccination against SARS-CoV-2 induces potent immune responses in people with HIV

Author

Fidler, S, Fox, J, Tipoe, T, Longet, S, Tipton, T, Abeywickrema, M, Adele, S, Alagaratnam, J, Ali, M, Aley, PK, Aslam, S, Balasubramanian, A, Bara, A, Bawa, T, Brown, A, Brown, H, Cappuccini, F, Davies, S, Fowler, J, Godfrey, L, Goodman, AL, Hilario, K, Hackstein, CP, Mathew, M, Mujadidi, YF, Packham, A, Petersen, C, Plested, E, Pollock, KM, Ramasamy, MN, Robinson, H, Robinson, N, Rongkard, P, Sanders, H, Serafimova, T, Spence, N, Waters, A, Woods, D, Zacharopoulou, P, Barnes, E, Dunachie, S, Goulder, P, Klenerman, P, Winston, A, Hill, AVS, Gilbert, SC, Carroll, M, Pollard, AJ, Lambe, T, Ogbe, A, and Frater, J

Abstract

BACKGROUND: People with HIV on antiretroviral therapy with good CD4 T cell counts make effective immune responses following vaccination against SARS-CoV-2. There are few data on longer term responses and the impact of a booster dose. METHODS: Adults with HIV were enrolled into a single arm open label study. Two doses of ChAdOx1 nCoV-19 were followed twelve months later by a third heterologous vaccine dose. Participants had undetectable viraemia on ART and CD4 counts >350 cells/µl. Immune responses to the ancestral strain and variants of concern were measured by anti-spike IgG ELISA, MesoScale Discovery (MSD) anti-spike platform, ACE-2 inhibition, Activation Induced Marker (AIM) assay and T cell proliferation. FINDINGS: 54 participants received two doses of ChAdOx1 nCoV-19. 43 received a third dose (42 with BNT162b2; 1 with mRNA-1273) one year after the first dose. After the third dose, total anti-SARS-CoV-2 spike IgG titres (MSD), ACE-2 inhibition and IgG ELISA results were significantly higher compared to Day 182 titres (P

Published
2022

20. Mitigation strategies to safely conduct HIV treatment research in the context of COVID-19

Author

Henderson, M, Fidler, S, Mothe, B, Grinsztejn, B, Haire, B, Collins, S, Lau, JSY, Luba, M, Sanne, I, Tatoud, R, Deeks, S, Lewin, SR, Henderson, M, Fidler, S, Mothe, B, Grinsztejn, B, Haire, B, Collins, S, Lau, JSY, Luba, M, Sanne, I, Tatoud, R, Deeks, S, and Lewin, SR

Abstract

INTRODUCTION: The International AIDS Society convened a multidisciplinary committee of experts in December 2020 to provide guidance and key considerations for the safe and ethical management of clinical trials involving people living with HIV (PLWH) during the SARS-CoV-2 pandemic. This consultation did not discuss guidance for the design of prevention studies for people at risk of HIV acquisition, nor for the programmatic delivery of antiretroviral therapy (ART). DISCUSSION: There is strong ambition to continue with HIV research from both PLWH and the research community despite the ongoing SARS-CoV-2 pandemic. How to do this safely and justly remains a critical debate. The SARS-CoV-2 pandemic continues to be highly dynamic. It is expected that with the emergence of effective SARS-CoV-2 prevention and treatment strategies, the risk to PLWH in clinical trials will decline over time. However, with the emergence of more contagious and potentially pathogenic SARS-CoV-2 variants, the effectiveness of current prevention and treatment strategies may be compromised. Uncertainty exists about how equally SARS-CoV-2 prevention and treatment strategies will be available globally, particularly for marginalized populations, many of whom are at high risk of reduced access to ART and/or HIV disease progression. All of these factors must be taken into account when deciding on the feasibility and safety of developing and implementing HIV research. CONCLUSIONS: It can be assumed for the foreseeable future that SARS-CoV-2 will persist and continue to pose challenges to conducting clinical research in PLWH. Guidelines regarding how best to implement HIV treatment studies will evolve accordingly. The risks and benefits of performing an HIV clinical trial must be carefully evaluated in the local context on an ongoing basis. With this document, we hope to provide a broad guidance that should remain viable and relevant even as the nature of the pandemic continues to develop.

Published
2022

24. Intimate Partner Violence (IPV) and Associated Factors in HPTN 071 (PopART) Study Communities in Zambia and South Africa-A Comparison by HIV Status

Author

Sabapathy, K, Stöckl, H, Mulubwa, C, Mubekapi-Musadaidzwa, C, Hoddinott, G, Floyd, S, Seeley, J, Bond, V, Bock, P, Fidler, S, Ayles, H, Hayes, R, and HPTN 071 (PopART) Study Team

Abstract

The HPTN 071(PopART) study was a community-randomised trial in Zambia and South Africa, examining the impact of combination-prevention including universal testing and treatment (UTT), on HIV-incidence. This sub-study evaluated factors associated with IPV (physical and/or sexual) to identify differences by HIV status. During 2015-16, a random subset of adults who participated in the first year of the PopART intervention were recruited and standardised questionnaires were administered. Logistic regression was performed to estimate odds ratios of factors associated with IPV. Among > 700 women studied (300 HIV-negative;400 HIV-positive), ~ 20% reported experiencing physical and/or sexual violence in the last 12-months. Sexual violence was similar by HIV status, but physical violence and reporting both physical/sexual violence was more common among HIV-positive women. Spending nights away from the community in the last 12-months was associated with higher odds of IPV among both HIV-negative (aOR 3.17, 95% CI 1.02-9.81) and HIV-positive women (aOR 1.79, 95% CI 0.99-3.24). Among HIV-positive women, financial autonomy was associated with reduced IPV (aOR:0.41,95%CI:0.23-0.75) while pregnancy in the last 12-months (aOR 2.25, 95% CI 1.07-4.74), risk of alcohol dependence (aOR 2.75, 95% CI 1.51-5.00) and risk of mental distress (aOR 2.62, 95% CI 1.33-5.16) were associated with increased IPV. Among HIV-negative women reporting sex in the last 12-months, transactional sex (aOR 3.97, 95% CI 1.02-15.37) and not knowing partner's HIV status (aOR 3.01, 95% CI 1.24-7.29) were associated with IPV. IPV was commonly reported in the study population and factors associated with IPV differed by HIV status. The association of mobility with IPV warrants further research. The high prevalence of harmful alcohol use and mental distress, and their association with IPV among HIV-positive women require urgent attention.

Published
2022

25. 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 G W, Kruiper, M S M, van der Bliek, G L, Bor, P C J, Debast, S B, Wagenvoort, G H J, Kroon, F P, de Boer, M G J, Jolink, H, Lambregts, M M C, Roukens, A H E, Scheper, H, Dorama, W, van Holten, N, Claas, E C J, Wessels, E, den Hollander, J G, El Moussaoui, R, Pogany, K, Smit, J V, Struik-Kalkman, D, van Niekerk, T, Pontesilli, O, Lowe, S H, Oude Lashof, A M L, Posthouwer, D, van Wolfswinkel, M E, Ackens, R P, Burgers, K, Schippers, J, Weijenberg-Maes, B, van Loo, I H M, Havenith, T R A, van Vonderen, M G A, Kampschreur, L M, Faber, S, Steeman-Bouma, R, Al Moujahid, A, Kootstra, G J, Delsing, C E, van der Burg-van de Plas, M, Scheiberlich, L, Kortmann, W, van Twillert, G, Renckens, R, Ruiter-Pronk, D, van Truijen-Oud, F A, Cohen Stuart, J W T, Jansen, E R, Hoogewerf, M, Rozemeijer, W, van der Reijden, W A, Sinnige, J C, Brinkman, K, van den Berk, G E L, Blok, W L, Lettinga, K D, de Regt, M, Schouten, W E M, Stalenhoef, J E, Veenstra, J, Vrouenraets, S M E, Blaauw, H, Geerders, G F, Kleene, M J, Kok, M, Knapen, M, van der Meché, I B, Mulder-Seeleman, E, Toonen, A J M, Wijnands, S, Wttewaal, E, Kwa, D, van Crevel, R, van Aerde, K, Dofferhoff, A S M, Henriet, S S V, Ter Hofstede, H J M, Hoogerwerf, J, Keuter, M, Richel, O, Albers, M, Grintjes-Huisman, K J T, de Haan, M, Marneef, M, Strik-Albers, R, Rahamat-Langendoen, J, Stelma, F F, Burger, D, Gisolf, E H, Hassing, R J, Claassen, M, Ter Beest, G, van Bentum, P H M, Langebeek, N, Tiemessen, R, Swanink, C M A, van Lelyveld, S F L, Soetekouw, R, van der Prijt, L M M, van der Swaluw, J, Bermon, N, Jansen, R, Herpers, B L, Veenendaal, D, Verhagen, D W M, Lauw, F N, van Broekhuizen, M C, van Wijk, M, Bierman, W F W, Bakker, M, Kleinnijenhuis, J, Kloeze, E, Middel, A, Postma, D F, Schölvinck, E H, Stienstra, Y, Verhage, A R, Wouthuyzen-Bakker, M, Boonstra, A, de Groot-de Jonge, H, van der Meulen, P A, de Weerd, D A, Niesters, H G M, van Leer-Buter, C C, Knoester, M, Hoepelman, A I M, Arends, J E, Barth, R E, Bruns, A H W, Ellerbroek, P M, Mudrikova, T, Oosterheert, J J, Schadd, E M, van Welzen, B J, Aarsman, K, Griffioen-van Santen, B M G, de Kroon, I, van Berkel, M, van Rooijen, C S A M, Schuurman, R, Verduyn-Lunel, F, Wensing, A M J, Bont, L J, Geelen, S P M, Loeffen, Y G T, Wolfs, T F W, Nauta, N, Rooijakkers, E O W, Holtsema, H, Voigt, R, van de Wetering, D, Alberto, A, van der Meer, I, Rosingh, A, Halaby, T, Zaheri, S, Boyd, A C, Bezemer, D O, van Sighem, A I, Smit, C, Hillebregt, M, de Jong, A, Woudstra, T, Bergsma, D, Meijering, R, van de Sande, L, Rutkens, T, van der Vliet, S, de Groot, L, van den Akker, M, Bakker, Y, El Berkaoui, A, Bezemer, M, Brétin, N, Djoechro, E, Groters, M, Kruijne, E, Lelivelt, K J, Lodewijk, C, Lucas, E, Munjishvili, L, Paling, F, Peeck, B, Ree, C, Regtop, R, Ruijs, Y, Schoorl, M, Schnörr, P, Scheigrond, A, Tuijn, E, Veenenberg, L, Visser, K M, Witte, E C, Van Frankenhuijsen, Maartje, Allegre, Thierry, Makhloufi, Djamila, Livrozet, Jean-Michel, Chiarello, Pierre, Godinot, Mathieu, Brunel-Dalmas, Florence, Gibert, Sylvie, Trepo, Christian, Peyramond, Dominique, Miailhes, Patrick, Koffi, Joseph, Thoirain, Valérie, Brochier, Corinne, Baudry, Thomas, Pailhes, Sylvie, Lafeuillade, Alain, Philip, Gisèle, Hittinger, Gilles, Assi, Assi, Lambry, Véronique, Rosenthal, Eric, Naqvi, Alissa, Dunais, Brigitte, Cua, Eric, Pradier, Christian, Durant, Jacques, Joulie, Aline, Quinsat, Denis, Tempesta, Serge, Ravaux, Isabelle, Martin, Isabelle Poizot, Faucher, Olivia, Cloarec, Nicolas, Champagne, Hélène, Pichancourt, Gilles, Morlat, Philippe, Pistone, Thierry, Bonnet, Fabrice, Mercie, Patrick, Faure, Isabelle, Hessamfar, Mojgan, Malvy, Denis, Lacoste, Denis, Pertusa, Marie-Carmen, Vandenhende, Marie-Anne, Bernard, Noëlle, Paccalin, François, Martell, Cédric, Roger-Schmelz, Julien, Receveur, Marie-Catherine, Duffau, Pierre, Dondia, Denis, Ribeiro, Emmanuel, Caltado, Sabrina, Neau, Didier, Dupont, Michel, Dutronc, Hervé, Dauchy, Frédéric, Cazanave, Charles, Vareil, Marc-Olivier, Wirth, Gaétane, Le Puil, Séverine, Pellegrin, Jean-Luc, Raymond, Isabelle, Viallard, Jean-François, Chaigne de Lalande, Severin, Garipuy, Daniel, Delobel, Pierre, Obadia, Martine, Cuzin, Lise, Alvarez, Muriel, Biezunski, Noemie, Porte, Lydie, Massip, Patrice, Debard, Alexa, Balsarin, Florence, Lagarrigue, Myriam, Prevoteau du Clary, François, Aquilina, Christian, Reynes, Jacques, Baillat, Vincent, Merle, Corinne, Lemoing, Vincent, Atoui, Nadine, Makinson, Alain, Jacquet, Jean Marc, Psomas, Christina, Tramoni, Christine, Aumaitre, Hugues, Saada, Mathieu, Medus, Marie, Malet, Martine, Eden, Aurélia, Neuville, Ségolène, Ferreyra, Milagros, Sotto, Albert, Barbuat, Claudine, Rouanet, Isabelle, Leureillard, Didier, Mauboussin, Jean-Marc, Lechiche, Catherine, Donsesco, Régine, Cabie, André, Abel, Sylvie, Pierre-Francois, Sandrine, Batala, Anne-Sophie, Cerland, Christophe, Rangom, Camille, Theresine, Nadine, Hoen, Bruno, Lamaury, Isabelle, Fabre, Isabelle, Schepers, Kinda, Curlier, Elodie, Ouissa, Rachida, Gaud, Catherine, Ricaud, Carole, Rodet, Roland, Wartel, Guillaume, Sautron, Carmele, Beck-Wirth, Geneviève, Michel, Catherine, Beck, Charles, Halna, Jean-Michel, Kowalczyk, Jakub, Benomar, Meryem, Drobacheff-Thiebaut, Christine, Chirouze, Catherine, Faucher, Jean-François, Parcelier, François, Foltzer, Adeline, Haffner-Mauvais, Cécile, Hustache Mathieu, Mathieu, Proust, Aurélie, Piroth, Lionel, Chavanet, Pascal, Duong, Michel, Buisson, Marielle, Waldner, Anne, Mahy, Sophie, Gohier, Sandrine, Croisier, Delphine, May, Thierry, Delestan, Mikael, Andre, Marie, Zadeh, Mahsa Mohseni, Martinot, Martin, Rosolen, Béatrice, Pachart, Anne, Martha, Benoît, Jeunet, Noëlle, Rey, David, Cheneau, Christine, Partisani, Maria, Priester, Michèle, Bernard-Henry, Claudine, Batard, Marie-Laure, Fischer, Patricia, Berger, Jean-Luc, Kmiec, Isabelle, Robineau, Olivier, Huleux, Thomas, Ajana, Faïza, Alcaraz, Isabelle, Allienne, Christophe, Baclet, Véronique, Meybeck, Agnès, 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
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26. COVAC1 phase 2a expanded safety and immunogenicity study of a self-amplifying RNA vaccine against SARS-CoV-2

Author

Szubert, AJ, Pollock, KM, Cheeseman, HM, Alagaratnam, J, Bern, H, Bird, O, Boffito, M, Byrne, R, Cole, T, Cosgrove, CA, Faust, SN, Fidler, S, Galiza, E, Hassanin, H, Kalyan, M, Libri, V, McFarlane, LR, Milinkovic, A, O'Hara, J, Owen, DR, Owens, D, Pacurar, M, Rampling, T, Skene, S, Winston, A, Woolley, J, Yim, YTN, Dunn, DT, McCormack, S, Shattock, RJ, and COVAC 1 Study Team

Subjects
General Medicine
Abstract

Background: lipid nanoparticle (LNP) encapsulated self-amplifying RNA (saRNA) is well tolerated and immunogenic in SARS-CoV-2 seronegative and seropositive individuals aged 18–75. Methods: a phase 2a expanded safety and immunogenicity study of a saRNA SARS-CoV-2 vaccine candidate LNP-nCoVsaRNA, was conducted at participating centres in the UK between 10th August 2020 and 30th July 2021. Participants received 1 μg then 10 μg of LNP-nCoVsaRNA, ∼14 weeks apart. Solicited adverse events (AEs) were collected for one week post-each vaccine, and unsolicited AEs throughout. Binding and neutralisating antiSARS-CoV-2 antibody raised in participant sera was measured by means of an anti-Spike (S) IgG ELISA, and SARS-CoV-2 pseudoneutralisation assay. (The trial is registered: ISRCTN17072692, EudraCT 2020-001646-20). Findings: 216 healthy individuals (median age 51 years) received 1.0 μg followed by 10.0 μg of the vaccine. 28/216 participants were either known to have previous SARS-CoV2 infection and/or were positive for anti-Spike (S) IgG at baseline. Reactogenicity was as expected based on the reactions following licensed COVID-19 vaccines, and there were no serious AEs related to vaccination. 80% of baseline SARS-CoV-2 naïve individuals (147/183) seroconverted two weeks post second immunization, irrespective of age (18–75); 56% (102/183) had detectable neutralising antibodies. Almost all (28/31) SARS-CoV-2 positive individuals had increased S IgG binding antibodies following their first 1.0 μg dose with a ≥0.5log10 increase in 71% (22/31). Interpretation: encapsulated saRNA was well tolerated and immunogenic in adults aged 18–75 years. Seroconversion rates in antigen naïve were higher than those reported in our dose-ranging study. Further work is required to determine if this difference is related to a longer dosing interval (14 vs. 4 weeks) or dosing with 1.0 μg followed by 10.0 μg. Boosting of S IgG antibodies was observed with a single 1.0 μg injection in those with pre-existing immune responses.Funding: grants and gifts from the Medical Research Council UKRI (MC_PC_19076), the National Institute for Health Research/Vaccine Task Force, Partners of Citadel and Citadel Securities, Sir Joseph Hotung Charitable Settlement, Jon Moulton Charity Trust, Pierre Andurand, and Restore the Earth.

Published
2023
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27. Immunotherapeutic approaches to HIV cure and remission

Author

Lee, MJ, Fidler, S, and Frater, J

Subjects
Microbiology (medical), CD4-Positive T-Lymphocytes, Immunomodulating Agents, Infectious Diseases, HIV-1, Humans, HIV Infections, Immunotherapy, Virus Latency
Abstract

Purpose of review Despite improvements in the effectiveness of antiretroviral therapy (ART), there are still unmet needs for people living with HIV which drive the search for a cure for HIV infection. The goal of this review is to discuss the challenges and recent immunotherapeutic advances towards developing a safe, effective and durable cure strategy for HIV. Recent findings In recent years, advances have been made in uncovering the mechanisms of persistence of latent HIV and in developing more accurate assays to measure the intact proviral reservoir. Broadly neutralising antibodies and modern techniques to enhance antibody responses have shown promising results. Other strategies including therapeutic vaccination, latency reversal agents, and immunomodulatory agents have shown limited success, but newer interventions including engineered T cells and other immunotherapies may be a potent and flexible strategy for achieving HIV cure. Summary Although progress with newer cure strategies may be encouraging, challenges remain and it is essential to achieve a high threshold of safety and effectiveness in the era of safe and effective ART. It is likely that to achieve sustained HIV remission or cure, a multipronged approach involving a combination of enhancing both adaptive and innate immunity is required.

Published
2021

28. Depressive symptoms and HIV risk behaviours among adolescents enrolled in the HPTN071 (PopART) trial in Zambia and South Africa

Author

Shanaube, K, Gachie, T, Hoddinott, G, Schaap, A, Floyd, S, Mainga, T, Bond, V, Hayes, R, Fidler, S, Ayles, H, and HPTN071 (PopART) Study Team

Subjects
South Africa, Cross-Sectional Studies, Risk-Taking, Multidisciplinary, Adolescent, Depression, Humans, Zambia, Female
Abstract

Background Mental health is a critical and neglected public health problem for adolescents in sub-Saharan Africa. In this paper we aim to determine the prevalence of depressive symptoms and the association with HIV risk behaviours in adolescents aged 15–19 years in Zambia and SA. Methods We conducted a cross-sectional survey from August-November 2017 in seven control communities of HPTN 071 (PopART) trial (a community-randomised trial of universal HIV testing and treatment), enrolling approximately 1400 eligible adolescents. HIV-status was self-reported. Depressive symptoms were measured with the Short Mood and Feelings Questionnaire (SMFQ), with a positive screen if adolescents scored ≥12. We fitted a logistic regression model to identify correlates of depressive symptoms with subgroup analyses among those who self-reported ever having had sex, by gender and country. Results Out of 6997 households approached, 6057 (86.6%) were enumerated. 2546 adolescents were enumerated of whom 2120 (83.3%) consented to participate and were administered the SMFQ. The prevalence of depressive symptoms was 584/2120 (27.6%) [95%CI: 25.7%-29.5%]. Adolescents in SA were less likely to experience depressive symptoms (Adjusted Odds Ratio [AOR] = 0.63 (95% CI: 0.50, 0.79), p-value Female adolescents (AOR = 1.46 (95% CI: 1.19, 1.81), p-value Conclusion The prevalence of depressive symptoms among adolescents ranged from 25–30% and was associated with increased HIV-risk behaviour.

Published
2022
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31. Expression of type I interferon-associated genes at antiretroviral therapy interruption predicts HIV virological rebound

Author

Zacharopoulou, P, Marchi, E, Ogbe, A, Robinson, N, Brown, H, Jones, M, Parolini, L, Pace, M, Grayson, N, Kaleebu, P, Rees, H, Fidler, S, Goulder, P, Klenerman, P, and Frater, J

Subjects
CD4-Positive T-Lymphocytes, Male, Multidisciplinary, Anti-HIV Agents, Science, Ubiquitin-Protein Ligases, HIV Infections, RNA sequencing, Article, Tripartite Motif Proteins, Withholding Treatment, HIV-1, Medicine, Cytokines, Humans, Infectious diseases, Female, Gene expression, Apoptosis Regulatory Proteins, Ubiquitin Thiolesterase, Ubiquitins, Adaptor Proteins, Signal Transducing, Transcription Factors
Abstract

Although certain individuals with HIV infection can stop antiretroviral therapy (ART) without viral load rebound, the mechanisms under-pinning ‘post-treatment control’ remain unclear. Using RNA-Seq we explored CD4 T cell gene expression to identify evidence of a mechanism that might underpin virological rebound and lead to discovery of associated biomarkers. Fourteen female participants who received 12 months of ART starting from primary HIV infection were sampled at the time of stopping therapy. Two analysis methods (Differential Gene Expression with Gene Set Enrichment Analysis, and Weighted Gene Co-expression Network Analysis) were employed to interrogate CD4+ T cell gene expression data and study pathways enriched in post-treatment controllers versus early rebounders. Using independent analysis tools, expression of genes associated with type I interferon responses were associated with a delayed time to viral rebound following treatment interruption (TI). Expression of four genes identified by Cox-Lasso (ISG15, XAF1, TRIM25 and USP18) was converted to a Risk Score, which associated with rebound (p

Published
2021

32. Psychotic disorders in young adults with perinatally acquired HIV: a UK case series.

Author

Mallik, I., Pasvol, T., Frize, G., Ayres, S., Barrera, A., Fidler, S., and Foster, C.

Subjects
BRAIN physiology, HIV infection complications, HIV-positive persons, PSYCHOSES, DISCRIMINATION (Sociology), RETROSPECTIVE studies, ANTIRETROVIRAL agents, EMIGRATION & immigration, ACQUISITION of data, RISK assessment, SOCIAL isolation, MEDICAL records, DESCRIPTIVE statistics, ETHNIC groups, VERTICAL transmission (Communicable diseases), ENVIRONMENTAL exposure, ADULTS
Abstract

Background: Increasing numbers of children with perinatally acquired HIV (PaHIV) are transitioning into adult care. People living with behaviourally acquired HIV are known to be at more risk of psychosis than uninfected peers. Young adults living with PaHIV face numerous risk factors; biological: lifelong exposure to a neurotrophic virus, antiretroviral medication and immune dysfunction during brain development, and environmental; social deprivation, ethnicity-related discrimination, and migration-related issues. To date, there is little published data on the prevalence of psychotic illness in young people growing up with PaHIV. Methods: We conducted a retrospective case note review of all individuals with PaHIV aged over 18 years registered for follow up at a dedicated clinic in the UK (n = 184). Results: In total, 12/184 (6.5%), median age 23 years (interquartile range 21–26), had experienced at least one psychotic episode. The presentation and course of the psychotic episodes experienced by our cohort varied from short-lived symptoms to long term illness and nine (75%) appear to have developed a severe and enduring mental illness requiring long term care. Conclusion: The prevalence of psychosis in our cohort was clearly above the lifetime prevalence of psychosis in UK individuals aged 16–34 years, which has been reported to be 0.5–1.0%. This highlights the importance of clinical vigilance regarding the mental health of young people growing up with PaHIV and the need to integrate direct access to mental health services within the HIV centres providing medical care. [ABSTRACT FROM AUTHOR]

Published
2022
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33. Uptake of HIV Testing Services Through Novel Community-Based Sexual and Reproductive Health Services: An Analysis of the Pilot Implementation Phase of the Yathu Yathu Intervention for Adolescents and Young People Aged 15–24 in Lusaka, Zambia

Author

Hensen, B., primary, Phiri, M., additional, Schaap, A., additional, Sigande, L., additional, Simwinga, M., additional, Floyd, S., additional, Belemu, S., additional, Simuyaba, M., additional, Shanaube, K., additional, Fidler, S., additional, Hayes, R., additional, and Ayles, H. M., additional

Published
2021
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34. Incoming HIV virion-derived Gag Spacer Peptide 2 (p1) is a target of effective CD8(+) T cell antiviral responses

Author

Yang, H, Llano, A, Cedeno, S, von Delft, A, Corcuera, A, Gillespie, GM, Knox, A, Leneghan, DB, Frater, J, Stohr, W, Fidler, S, Mothe, B, Mak, Johnson, Brander, C, Ternette, N, Dorrell, L, Yang, H, Llano, A, Cedeno, S, von Delft, A, Corcuera, A, Gillespie, GM, Knox, A, Leneghan, DB, Frater, J, Stohr, W, Fidler, S, Mothe, B, Mak, Johnson, Brander, C, Ternette, N, and Dorrell, L

Published
2021

35. HIV cure research in the time of COVID-19 - Antiretroviral therapy treatment interruption trials: A discussion paper

Author

Fidler, S, Lewin, S, Deeks, S, Sogaard, OS, Vandekerckhove, L, Collins, S, Kelly, D, Singh, J, Caskey, M, Frater, J, Fidler, S, Lewin, S, Deeks, S, Sogaard, OS, Vandekerckhove, L, Collins, S, Kelly, D, Singh, J, Caskey, M, and Frater, J

Abstract

This discussion paper addresses the safety of HIV cure studies, particularly those involving stopping antiretroviral therapy, known as an analytic treatment interruption (ATI) in the context of the SARS-CoV-2 pandemic. More than 30 studies listed on ClinicalTrials.gov include an ATI and many others were planned to begin over the next 12 months but most were halted due to the COVID-19 pandemic. We consider the ethics, risks and practical considerations to be taken into account before re-opening HIV cure clinical trials, noting the specific risks of ATI in the context of circulating SARS-CoV-2.

Published
2021

36. 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

39. Immune response regulation gene signatures predict time to viral rebound after antiretroviral treatment interruption in primary HIV infection

Author

Zacharopoulou, P, Marchi, E, Jones, M, Robinson, N, Brown, H, Fidler, S, Frater, J, and Imperial College Healthcare NHS Trust- BRC Funding

Subjects
Science & Technology, Infectious Diseases, Virology, 1103 Clinical Sciences, Life Sciences & Biomedicine
Abstract

Background: Antiretroviral therapy (ART) can maintain undetectable plasma HIV viraemia, but on stopping therapy HIV can be detected in the blood (‘viral rebound’), generally within a few weeks. For some individuals, the time to rebound may be protracted – up to months or years – and in some ‘post‐treatment controllers’ no rebound is reported. Method: To explore the molecular differences between early and late rebounders, we present a longitudinal analysis of the host transcriptome that explores key genetic signatures associated with time to HIV rebound. We sequenced expressed host mRNA from South African women enrolled in the SPARTAC clinical trial, and who received treatment for up to 48 weeks, starting in primary infection. We studied CD4+ T‐cells sampled at ‘baseline’ before ART initiation and again at treatment interruption (wk 48). We used R and limma with voom to quantify and transform our data and Gene Set Enrichment Analysis software with the Reactome database to identify putative genetic signatures associated with clinical outcomes Results: We find statistically significant enrichment of over 20 gene sets when comparing different ‘time to rebound’ phenotypes. We show that gene sets involved in the regulation of the immune response, in particular the Interferon Type I and the Immunoregulatory interactions between lymphoid and non‐lymphoid cells sets are up‐regulated in late versus early rebounders as well as rebounders versuslikely elite controllers. Notably, pre‐ and post‐ART samples seem to share pathway enrichment in the aforementioned gene sets. Conclusion: These data suggest that specific components of the immune response may predict rapid rebound, post‐treatment control,and elite control and may help discovery of prognostic biomarkers for time to rebound and new interventions targeted at drug‐free HIV remission.

Published
2020

40. Prospective interruption of therapy towards a cure for HIV (PITCH): experiences of patients on treatment interruption (TI)

Author

Nkhoma, K, Lwanga, J, Ryan, F, Lee, M, Bristowe, K, Harding, R, Fidler, S, Frater, J, Fox, J, and Imperial College Healthcare NHS Trust- BRC Funding

Subjects
Science & Technology, Infectious Diseases, Virology, 1103 Clinical Sciences, Life Sciences & Biomedicine
Abstract

Background: Increasingly cure trials require a treatment interruption (TI) in order to evaluate whether an intervention has worked. In order to ensure that future TI trials are designed sensitively with participants at the heart of the process, we carried out qualitative interviews with individuals taking part in the PITCH TI study. Method: We recruited participants with primary HIV infection, who commenced ART within three months of diagnosis, have been on ART for at least two years with HIV‐1 DNA levels 500 or CD4:8 ratio> 1, with suppressed plasma VL < 50 copies HIV RNA/ml. Upon ART cessation, for the first 12 weeks participants were required to undergo point‐ of‐care quantitative GeneXpert viral load testing on a twice per week basis, with additional visits if desired. In‐depth qualitative face‐to‐face interviews were conducted two weeks before, at least two weeks during and two weeks after TI. The interviews aimed to explore views and experiences about TI. Results: Five out of six participants participated: n=3 were interviewed before TI, n=5 were interviewed during TI and n=4 were interviewed after TI. Seven themes were identified: 1) Motivation to participate: all participants reported participation in TI was to help others in future. 2) Benefits of TI: Stopped experiencing ART side effects and being off treatment saved NHS money. 3) Challenges of TI: frequent appointments with NHS for blood test. 4) Risks associated with TI: passing on HIV if detectable. Participants used prevention tools (PrEP/condoms). 5) Vicious cycle of worry: anxious/worried their viral load was going up and that they might transmit HIV. 6) Being undetectable: participants knew that undetectable=untransmittable. 7) Treatment rotation: TI is not a cure butswapping treatment with the partner who has to take PrEP. Conclusion: Participants found that taking a TI as part of a cure trial to be a positive experience and valued the break from taking treatment every day. However psychosocial consideration should be incorporated into planning for TI studies including family/partner involvement. TI studies should provide PrEP to partners of participants as a risk reduction tool and have strategies to reduce participant anxiety during the TI phase.

Published
2020

41. What do the Universal Test and Treat trials tell us about the path to HIV epidemic control?

Author

Havlir, D., Lockman, S., Ayles, H., Larmarange, Joseph, Chamie, G., Gaolathe, T., Iwuji, C., Fidler, S., Kamya, M., Floyd, S., Moore, J., Hayes, R., Petersen, M., Dabis, F., and Universal Test Treat Trials UT3 Consortium

Subjects
Adult, Male, Adolescent, Anti-HIV Agents, HIV elimination, HIV prevention, antiretroviral therapy, Clinical Trials and Supportive Activities, Clinical Sciences, Zambia, Treat Trials) UT3 Consortium, HIV Infections, universal access, Time-to-Treatment, South Africa, Clinical Research, Behavioral and Social Science, Prevalence, Humans, Mass Screening, HIV care continuum, Uganda, Epidemics, Pediatric, Botswana, Other Medical and Health Sciences, Incidence, Prevention, public health, AIDS Serodiagnosis, Viral Load, Kenya, HIV testing, Good Health and Well Being, Mental Health, Infectious Diseases, Public Health and Health Services, HIV/AIDS, Female, (Universal Test, Infection
Abstract

IntroductionAchieving HIV epidemic control globally will require new strategies to accelerate reductions in HIV incidence and mortality. Universal test and treat (UTT) was evaluated in four randomized population-based trials (BCPP/Ya Tsie, HPTN 071/PopART, SEARCH, ANRS 12249/TasP) conducted in sub-Saharan Africa(SSA) during expanded antiretroviral treatment (ART) eligibility by World Health Organization guidelines and the UNAIDS 90-90-90 campaign.DiscussionThese three-year studies were conducted in Botswana, Zambia, Uganda, Kenya and South Africa in settings with baseline HIV prevalence from 4% to 30%. Key observations across studies were: (1) Universal testing (implemented via a variety of home and community-based testing approaches) achieved >90% coverage in all studies. (2) When coupled with robust linkage to HIV care, rapid ART start and patient-centred care, UTT achieved among the highest reported population levels of viral suppression in SSA. Significant gains in population-level viral suppression were made in regions with both low and high baseline population viral load; however, viral suppression gains were not uniform across all sub-populations and were lower among youth. (3) UTT resulted inmarked reductions in community HIV incidence when universal testing and robust linkage were present. However, HIV elimination targets were not reached. In BCPP and HPTN 071, annualized HIV incidence was approximately 20% to 30% lower in the intervention (which included universal testing) compared to control arms (no universal testing). In SEARCH (where both arms had universal testing), incidence declined 32% over three years. (4) UTT reduced HIV associated mortality by 23% in the intervention versus control communities in SEARCH, a study in whichmortality was comprehensively measured.ConclusionsThese trials provide strong evidence that UTT inclusive of universal testing increases population-level viral suppression and decreases HIV incidence and mortality faster than the status quo in SSA and should be adapted at a sub-country level as a public health strategy. However, more is needed, including integration of new prevention interventions into UTT, in order to reach UNAIDS HIV elimination targets.

Published
2020

42. PCR134 Associations between HIV Stigma and Health-Related Quality of Life Among People Living with HIV in Zambia and South Africa: A Cross-Sectional Analysis of Data from the HPTN 071 (POPART) Study

Author

Hall, E., Davis, K., Ohrnberger, J., Pickles, M., Gregson, S., Thomas, R., Hargreaves, J.R., Pliakas, T., Bwalya, J., Dunbar, R., Mainga, T., Shanaube, K., Hoddinott, G., Bond, V., Bock, P., Ayles, H., Stangl, A., Donnell, D., Hayes, R., Fidler, S., and Hauck, K.

Published
2023
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43. Levels of Human Immunodeficiency Virus DNA Are Determined Before ART Initiation and Linked to CD8 T-Cell Activation and Memory Expansion

Author

Martin, GE, Pace, M, Shearer, FM, Zilber, E, Hurst, J, Meyerowitz, J, Thornhill, JP, Lwanga, J, Brown, H, Robinson, N, Hopkins, E, Olejniczak, N, Nwokolo, N, Fox, J, Fidler, S, Willberg, CB, Frater, J, Martin, GE, Pace, M, Shearer, FM, Zilber, E, Hurst, J, Meyerowitz, J, Thornhill, JP, Lwanga, J, Brown, H, Robinson, N, Hopkins, E, Olejniczak, N, Nwokolo, N, Fox, J, Fidler, S, Willberg, CB, and Frater, J

Abstract

Initiation of antiretroviral therapy (ART) in early compared with chronic human immunodeficiency virus (HIV) infection is associated with a smaller HIV reservoir. This longitudinal analysis of 60 individuals who began ART during primary HIV infection (PHI) investigates which pre- and posttherapy factors best predict HIV DNA levels (a correlate of reservoir size) after treatment initiation during PHI. The best predictor of HIV DNA at 1 year was pre-ART HIV DNA, which was in turn significantly associated with CD8 memory T-cell differentiation (effector memory, naive, and T-bet-Eomes- subsets), CD8 T-cell activation (CD38 expression) and T-cell immunoglobulin and mucin-domain containing-3 (Tim-3) expression on memory T cells. No associations were found for any immunological variables after 1 year of ART. Levels of HIV DNA are determined around the time of ART initiation in individuals treated during PHI. CD8 T-cell activation and memory expansion are linked to HIV DNA levels, suggesting the importance of the initial host-viral interplay in eventual reservoir size.

Published
2020

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