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, Mamadou H Diallo, Nuala McGrath, Collins Iwuji, Mélanie Plazy, Rodolphe Thiébaut, Frank Tanser, Till Bärnighausen, Joanna Orne-Gliemann, Deenan Pillay, François Dabis, ANRS 12249 TasP Study Group, Till Barnighausen, Kobus Herbst, Collins Iwuji, Thembisa Makowa, Kevi Naidu, Nonhlanhla Okesola, Tulio Oliveira, Deenan Pillay, Tamsen Rochat, Frank Tanser, Johannes Viljoen, Thembelihle Zuma, Frank Tanser, Nuala McGrath, Tulio Oliveira, Eric Balestre, Francois Dabis, Sophie Karcher, Joanna Orne-Gliemann, Melanie Plazy, Melanie Prague, Rodolphe Thiebaut, Thierry Tiendrebeogo, Sylvie Boyer, Hermann Donfouet, Andrea Gosset, Laura March, Camelia Protopopescu, Bruno Spire, Joseph Larmarange, Vincent Calvez, Anne Derache, Anne-Genevieve Marcelin, Rosemary Dray-Spira, France Lert, Kamal El Farouki, Marie-Laure Chaix, Brigitte Bazin, Claire Rekacewicz, Collins Iwuji, John Imrie, Deenan Pillay, Nuala McGrath, Richard Lessells, Collins Iwuji, Nuala McGrath, Colin Newell, Marie-Louise Newell, Alexandra Calmy, Kenneth Freedberg, Till Barnighausen, Jan Hontelez, Till Barnighausen, Jan Hontelez, Joseph Larmarange, Mamadou H Diallo, Nuala McGrath, Collins Iwuji, Mélanie Plazy, Rodolphe Thiébaut, Frank Tanser, Till Bärnighausen, Joanna Orne-Gliemann, Deenan Pillay, François Dabis, ANRS 12249 TasP Study Group, Till Barnighausen, Kobus Herbst, Collins Iwuji, Thembisa Makowa, Kevi Naidu, Nonhlanhla Okesola, Tulio Oliveira, Deenan Pillay, Tamsen Rochat, Frank Tanser, Johannes Viljoen, Thembelihle Zuma, Frank Tanser, Nuala McGrath, Tulio Oliveira, Eric Balestre, Francois Dabis, Sophie Karcher, Joanna Orne-Gliemann, Melanie Plazy, Melanie Prague, Rodolphe Thiebaut, Thierry Tiendrebeogo, Sylvie Boyer, Hermann Donfouet, Andrea Gosset, Laura March, Camelia Protopopescu, Bruno Spire, Joseph Larmarange, Vincent Calvez, Anne Derache, Anne-Genevieve Marcelin, Rosemary Dray-Spira, France Lert, Kamal El Farouki, Marie-Laure Chaix, Brigitte Bazin, Claire Rekacewicz, Collins Iwuji, John Imrie, Deenan Pillay, Nuala McGrath, Richard Lessells, Collins Iwuji, Nuala McGrath, Colin Newell, Marie-Louise Newell, Alexandra Calmy, Kenneth Freedberg, Till Barnighausen, Jan Hontelez, Till Barnighausen, Jan Hontelez

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 × 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; South Africa; antiretroviral therapy; population health; retention in care; sustained viral suppression.

© 2019 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.

Figures

Figure 1
Figure 1
Dates of home‐based survey rounds activities by clusters, ANRS 12249 TasP trial (2012 to 2016). The light areas in round 1 indicate the time required to complete the initial census of the resident population.
Figure 2
Figure 2
Referral to trial clinics, entry into care, ART status at clinic entry, CD4 count and ART initiation by trial arm, ANRS 12249 TasP trial (2012 to 2016). Threshold was equal to 350 cells/mm3 before 1 January 2015, and to 500 cells/mm3 thereafter.
Figure 3
Figure 3
Population viral suppression over calendar time (a) and time since cluster opening (b), by cluster, year of cluster opening and trial arm, ANRS 12249 TasP trial (2012 to 2016). Each grey line represents a different cluster.
Figure 4
Figure 4
Effect of calendar time, time since cluster opening and trial arm on the different subcomponents of the HIV care cascade, ANRS 12249 TasP trial (2012 to 2016). Model 1 is adjusted on calendar time, time since cluster opening and trial arm. Model 2 is also adjusted on cluster‐level sociodemographic characteristics.

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Source: PubMed

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