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Temporal trends of population viral suppression in the context of Universal Test and Treat: the ANRS 12249 TasP trial in rural South Africa

Joseph Larmarange 1 Mamadou Diallo 1 Nuala Mcgrath 2 Collins Iwuji 3 Mélanie Plazy 4 Rodolphe Thiébaut 4 Frank Tanser 5 Till Bärrnighausen 6 Joanna Orne‐gliemann 4 Deenan Pillay 7 Francois Dabis 4 Kobus Herbst 5 Thembisa Makowa 5 Kevi Naidu 5 Nonhlanhla Okesola 5 Tamsen Rochat 8 Johannes Viljoen 9 Thembelihle Zuma 5 Tulio Oliveira 5 Sophie Karcher 10 Mélanie Prague 10 Thierry Tiendrebeogo 11 Sylvie Boyer 12 Hermann Donfouet 12 Andréa Gosset 12 Laura March 12 Camelia Protopopescu 12 Bruno Spire 12 Vincent Calvez 13 Anne Derache 14 Anne‐genevieve Marcelin 15 Rosemary Dray‐spira 16 France Lert 17 Kamal El Farouki 16 Marie‐laure Chaix 18 Brigitte Bazin 19 Claire Rekacewicz 19 John Imrie 7 Richard Lessells 8 Colin Newell 20 Marie‐louise Newell 20 Alexandra Calmy 21 Kenneth Freedberg 22 Jan Hontelez 23
1 CEPED - UMR_D 196 - Centre population et développement
2 LSHTM - London School of Hygiene and Tropical Medicine
3 BSMS - Brighton and Sussex Medical School
4 ISPED - Institut de Santé Publique, d'Epidémiologie et de Développement
5 AHRI - Africa Health Research Institute [Durban/Mtubatuba]
6 Harvard School of Public Health
7 UCL - University College of London [London]
8 Africa Centre for Health and Population Studies
9 Pathogénèse et contrôle des infections chroniques (PCCI)
10 Epidémiologie et Biostatistique [Bordeaux]
11 BPH - Bordeaux population health
12 SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD - Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale
13 iPLESP - Institut Pierre Louis d'Epidémiologie et de Santé Publique
14 iPLESP - Institut Pierre Louis d'Epidémiologie et de Santé Publique
15 Epidémiologie, Systèmes d'Information, Modélisation
16 U1018 (Équipe 9) - Mode de vie, génétique et santé : études intégratives et transgénérationnelles
CESP - Centre de recherche en épidémiologie et santé des populations, IGR - Institut Gustave Roussy
17 CESP - Centre de recherche en épidémiologie et santé des populations
18 AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP)
19 ANRS - Agence Nationale de Recherches sur le Sida et les Hépatites Virales
20 University of Southampton
21 Hôpital Universitaire de Genève
22 Massachusetts General Hospital [Boston]
23 Heidelberg University
Abstract : Introduction: The universal test-and-treat (UTT) strategy aims to maximize population viral suppression (PVS), that is, the proportion of all people living with HIV (PLHIV) on antiretroviral treatment (ART) and virally suppressed, with the goal of reducing HIV transmission at the population level. This article explores the extent to which temporal changes in PVS explain the observed lack of association between universal treatment and cumulative HIV incidence seen in the ANRS 12249 TasP trial conducted in rural South Africa. Methods: The TasP cluster-randomized trial (2012 to 2016) implemented six-monthly repeat home-based HIV counselling and testing (RHBCT) and referral of PLHIV to local HIV clinics in 2 9 11 clusters opened sequentially. ART was initiated according to national guidelines in control clusters and regardless of CD4 count in intervention clusters. We measured residency status, HIV status, and HIV care status for each participant on a daily basis. PVS was computed per cluster among all resident PLHIV (≥16, including those not in care) at cluster opening and daily thereafter. We used a mixed linear model to explore time patterns in PVS, adjusting for sociodemographic changes at the cluster level. Results: 8563 PLHIV were followed. During the course of the trial, PVS increased significantly in both arms (23.5% to 46.2% in intervention, +22.8, p < 0.001; 26.0% to 44.6% in control, +18.6, p < 0.001). That increase was similar in both arms (p = 0.514). In the final adjusted model, PVS increase was most associated with increased RHBCT and the implementation of local trial clinics (measured by time since cluster opening). Contextual changes (measured by calendar time) also contributed slightly. The effect of universal ART (trial arm) was positive but limited. Conclusions: PVS was improved significantly but similarly in both trial arms, explaining partly the null effect observed in terms of cumulative HIV incidence between arms. The PVS gains due to changes in ART-initiation guidelines alone are relatively small compared to gains obtained by strategies to maximize testing and linkage to care. The achievement of the 90-90-90 targets will not be met if the operational and implementational challenges limiting access to care and treatment, often context-specific, are not properly addressed. Clinical trial number: NCT01509508 (clinicalTrials.gov)/DOH-27-0512-3974 (South African National Clinical Trials Register).
Keywords : HIV antiretroviral therapy sustained viral suppression retention in care population health South Africa
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UNIV-AMU | UVSQ | CESP | IRD | IPLESP | UNIV-MONTPELLIER | U1252 | SU-MEDECINE | BS | UP-SOCIETES-HUMANITES | INSERM | SORBONNE-UNIVERSITE | UNIV-PARIS-SACLAY | SU-TI | U1219 | FNCLCC | PCCI

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Joseph Larmarange, Mamadou Diallo, Nuala Mcgrath, Collins Iwuji, Mélanie Plazy, et al.. Temporal trends of population viral suppression in the context of Universal Test and Treat: the ANRS 12249 TasP trial in rural South Africa. Journal of the International AIDS Society, BioMed Central (2008-2012) ; International Aids Society (2008-) ; Wiley (2017-), 2019, 22 (10), ⟨10.1002/jia2.25402⟩. ⟨hal-03161847v3⟩

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