Introduction
Overview of the ANRS 12249 Cluster-Randomized Trial
Results of the ANRS 12249 Cluster-Randomized Trial
Key Insights from the ANRS 12249 Cluster-Randomized Trial
In this vein, the SEARCH trial model (described in detail elsewhere [20]) of taking a community-based, multi-disease approach for the management and treatment of HIV would seem to hold considerable promise.There are those who are still not keen [to attend the TasP clinic]. They have a problem that they will be seen at the park home [TasP clinic] and they say that the park home is full of people who have HIV. You see it is something like that. You see there are people who go to the clinic not because they are going to check their own illnesses but they keep looking at the people who are going to the research clinic and they say we are even carrying babies who have HIV. Now when a lot of people think about that they think if you go to that clinic you are visible, they wish they can hide from others. (Female, 51 years)
Overview of the AHRI Population-Based Cohort
Key Findings from the AHRI Population-Based Cohort
Study | Period and participants | Objectives | Results | Sample size (N); effect estimate (95% CI); P value | Differential in ART coverage or other indicators | Conclusion |
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Tanser et al. [44••] | 2004–2011; women aged 15–49 years, men aged 15–54 years | To measure the effect of community-level ART coverage on HIV incidence, controlling for multiple socio-demographic, behavioural, and community variables. | An HIV-uninfected individual living in a community with high ART coverage (30 to 40% of all HIV-infected individuals on ART) was 37% less likely to acquire HIV than someone living in a community where ART coverage was low (< 10% of all HIV-infected individuals on ART). | N = 16,667; aHR = 0.63 (0.44–0.91); P = 0.013 | 30–40% vs. < 10% | Population-level reductions in the transmission of HIV can be achieved in nurse-led, devolved, public-sector ART programs in rural sub-Saharan African settings where complete coverage of therapy under existing treatment guidelines has not yet been attained. |
Vandormael et al. [46] | 2004–2012; women aged 15–49 years, men aged 15–54 years | To measure the effect of ART usage in the household on HIV incidence, controlling for multiple socio-demographic, behavioural, and community variables. | An HIV-uninfected individual living in a household with high opposite-sex ART coverage (50 to 60%) was 26% less likely to acquire HIV than someone living in a household with a low opposite-sex ART coverage (< 10%). | N = 14,505; aHR = 0.74 (0.61–0.91); P < 0.05 | 50–60% vs. < 10% | Results provide further evidence that ART significantly reduces the risk of onward transmission of HIV in a real-world setting. Awareness that ART can prevent transmission to co-resident sexual partners could be a powerful motivator for HIV testing and ART uptake, retention, and adherence. |
Wirth et al. [45] | 2004–2011; women aged 15–49 years, men aged 15–54 years | To evaluate the impact of community ART coverage on HIV incidence risk using an instrumental variable (IV) approach. The IV approach was used to account for the possibility that individuals living in high ART coverage areas may systematically differ from those in low ART coverage areas even after controlling for multiple predictors of infection. | In the IV-adjusted model, persons in communities with > 40% ART coverage were 62% less likely to acquire HIV infection than persons in communities with < 10% ART coverage. | Person-years = 53,605; aHR = 0.38 (0.17–0.84); P < 0.001 | > 40% vs. < 10% | The findings indicate that the effect of community-level ART coverage on HIV incidence was not only robust to unmeasured confounding but may be stronger than previously reported in Tanser et al. [44••] |
Oldenburg et al. [49] | 2005–2013; women and men aged > 15 years | To evaluate the preventative impact of ART on HIV incidence in stable sero-discordant couples, controlling for multiple socio-demographic, behavioural, and community variables. | Use of ART was associated with a 77% decrease in HIV incidence risk among sero-discordant couples. | N = 17,016 and n = 2042 (discordant couples); aHR = 0.23 (0.07–0.80); P = 0.02 | On ART vs. not on ART | ART initiation was associated with a large reduction in HIV incidence in sero-discordant couples in rural KwaZulu-Natal. |
Tanser et al. [48] | 2011–2015; women aged 15–49 years, men aged 15–54 years | To empirically quantify the relationship between a range of population viral load (PVL) measures and the prospective risk of HIV incidence among participants who were HIV-negative at baseline. Analyses were controlled for multiple socio-demographic, behavioural, and community variables. | Prospective HIV incidence in communities where the population prevalence of detectable viremia in the 1st quartile (< 12%) was 37% lower compared to communities in the 4th quartile (> 19%). | N = 8732; aHR = 0.63 (0.52–0.77); P < 0.001 | Population prevalence of detectable viremia > 19% (4th quantile) vs. 12% (1st quantile) | Results show a clear relationship between PVL measures such as the population prevalence of detectable viremia and prospective incidence of HIV infection. PVL indices could play a key role in targeting and monitoring interventions in the most vulnerable communities where the future rate of new HIV infections is likely to be highest. |
Iwuji et al. [3••] | 2012–2016; resident men and women aged > 16 years | To investigate the effect of universal test and treat on HIV incidence using a cluster-randomized trial. The intervention group received immediate ART initiation upon HIV diagnosis. The control group had ART initiation at CD4 T cell counts < 350 and < 500 cells/μl upon HIV diagnosis (following national eligibility guidelines). | HIV incidence was 2.11 per 100 person-years (95% CI 1.84–2.39) in the intervention group and 2.27 per 100 person-years (2.00–2.54) in the control group. | N = 26,518; aHR = 1.01 (0.87–1.17); P = 0.89 | 45% ART coverage (in the treatment group) vs. 43% (in the control group) | There was no difference in HIV incidence between the intervention and control groups. Absence of a lowering of HIV incidence in universal test and treat clusters occurred as a consequence of there being no difference in ART coverage and population-level viral suppression between control and intervention communities. |
Oldenburg et al. [47] | 2007–2011, women and men aged > 15 years | To investigate the effect of immediate vs. delayed ART on HIV incidence among household members. The study used a quasi-experimental approach (regression discontinuity), which is designed to improve causal inference in nonrandomized studies. | Compared with delayed ART initiation, immediate initiation reduced HIV incidence in households by 47% and by 32–60% in alternate specifications of the model. | N = 4115; aHR = 0.53 (0.30–0.96); P < 0.05 | Threshold of 200 CD4+ count cell/μl used to determine immediate vs. delayed initiation | This study demonstrates for the first time causally some of the spill-over effects that contribute to the population impact of HIV treatment on HIV incidence. |
Vandormael et al. [38] | 2005–2017; women aged 15–49 years, men aged 15–54 years | To quantify trends in the incidence to mortality ratio (IMR) between 2005 and 2017. The UNAIDS has proposed IMR as a key measure of epidemic control [51]. Epidemic control is achieved when the ratio of new infections to the number of all-cause HIV-related deaths falls below 1. | The observed IMR peaked at 5.74 in 2013 before declining to 4.06 in 2017. Bootstrapped estimates show an IMR reduction of 25% during this period. | N = 22,758 (HIV− cohort) and N = 13,460 (HIV+ cohort); IMR = 0.75 (0.69–0.85); P < 0.05 | ART coverage increased from 2% in 2005 (CD4+ count < 200 cells/μl) to 30% in 2011 (< 350 cells/μl) to 47% in 2016 (all eligible) and to 46% in 2017. | The results show impressive progress toward HIV epidemic control in the study area. However, the IMR epidemic threshold < 1 was not reached in 2017. Progress is off track for 2020 targets set by the UNAIDS. |
Vandormael et al. [38] | 2005–2017; women aged 15–49 years, men aged 15–54 years | To quantify trends in the incidence to prevalence ratio (IPR) between 2005 and 2017. The IPR is another metric of HIV epidemic control proposed by UNAIDS. Epidemic control is achieved when there is less than one new HIV infection over a 33-year period on ART. The average survival time of a newly infected person on ART is 33 years, which translates into 1/33 or 3 new infections per 100 people living with HIV per year.[51] | The IPR declined from 0.144 in 2012 to 0.075 in 2017. Bootstrapped estimates show an IPR reduction of 54% during this period. | N = 39,735 (HIV prevalence); N = 22,758 (HIV− cohort) IPR = 0.46 (0.34–0.62); P < 0.05 | ART coverage increased from 2% in 2005 (CD4+ count < 200 cells/μl) to 30% in 2011 (< 350 cells/μl) to 47% in 2016 (all eligible) and to 46% in 2017. | The decline in this metric indicates further progress toward HIV epidemic control in the study area. However, the epidemic threshold of < 0.03 was not reached in 2017. Progress is off track for 2020 targets set by the UNAIDS. |
Tomita et al. [50] | 2009–2015; men and women aged > 15 years | To quantify the impact of community coverage of ART on recently diagnosed TB disease, controlling for multiple socio-demographic, behavioural, and community variables. | Living in a community with ART coverage ≥ 50% was associated with a 34% decrease in the odds of recently diagnosed TB vs. living in a community with ART coverage < 50%. | N = 41,812; aOR = 0.66 (0.49–0.88); P = 0.005 | ART coverage ≥50% vs. < 50% | Results indicate the potential benefit of increased community ART coverage in lowering the risk of active tuberculosis highlighting the need to prioritize the expansion of such effective population interventions targeting high-risk areas. |
Vandormael et al. [43•] | 2005–2017; women aged 15–49 years, men aged 15–54 years | To quantify trends in the population-wide HIV incidence following ART scale-up, controlling for multiple socio-demographic, behavioural, and community variables. | The HIV incidence rate declined from 3.94 (95% CI 3.37–4.60) to 2.25 (1.79–2.83) events per 100 person-years between 2012 and 2017—a reduction of 43%. | N = 22,239; IRR = 0.57 (0.43–0.75); P < 0.001 | ART coverage increased from 2% in 2005 (CD4+ count < 200 cells/μl) to 30% in 2011 (< 350 cells/μl) to 47% in 2016 (all eligible) and to 46% in 2017. | The study shows robust evidence of large HIV incidence declines among men and women, which are consistent with the scale-up of ART and VMMC services. |