Study Objectives
Primary Objectives
- To determine whether implementation of an enhanced combination prevention (CP) package can significantly reduce population-level, cumulative HIV incidence in 16-64 year old residents in Botswana over a period of 36 months.
- To estimate population-level uptake of HIV testing, ART, male circumcision, and PMTCT services and compare service uptake between Standard of Care (SOC) and Intervention communities at baseline and at study end.
- To estimate the cost per additional HIV infection averted in intervention compared with standard of care communities.
Secondary Objectives
- To estimate the extent to which incident HIV infections in intervention and in SOC communities arise from HIV strains circulating within communities randomized to the same study arm as the incident case or from strains circulating outside those communities (sexual network mixing) by: (1) genotyping the circulating HIV-1 variants in SOC and intervention arms, and (2) estimating the proportions of new HIV infections that can and cannot be phylogenetically linked to HIV-infected persons in the same study arm.
- To estimate the efficacy of the Combination Prevention package on reducing the rate of new infections with HIV strains circulating within communities in the same study arm.
- In the intervention arm only, to estimate over time, the proportion of incident HIV-1-infections that can be linked to HIV-infected adults of the same study arm.
- During the end of study survey (ESS) to compare Combination Prevention (CP) package uptake within 20% households with CP package uptake in the broader communities they represent.
- To obtain secondary cross-sectional estimates of community HIV incidence at baseline and study end in SOC and intervention communities through use of HIV-incidence assays.
- At baseline, during study conduct, and at study end, to describe the proportion of recent HIV infections in intervention and standard of care communities with evidence of transmitted HIV drug resistance.
- To estimate the proportion of HIV-infected adults with undetectable viral load (VL<400 copies/ml) at baseline, during study conduct, and study end in intervention and SOC communities.
- To estimate the association between HIV-1 viral load and HIV transmissions using viral linkage data.
- To project HIV infections and deaths (attributable to AIDS) averted in the intervention and standard of care communities beyond the time frame of the trial.
- To estimate the cost of provision of intervention services.
- To estimate the cost-effectiveness of combination prevention (taking into account both infections averted and clinical costs) using the two arms from the trial as well as an additional model-based strategy.
Study Design: The Ya Tsie study was a pair-matched community randomized trial, meaning that 30 study communities were matched, based on similarities, into 15 pairs.
In each pair, one community was randomly chosen as the intervention community in which universal test and treat and other interventions were rolled out. The other community in the pair acted as a control and received the standard of care, as well as extra support in the form of HIV testing and referral for Household Survey participants. Residents of all 30 communities could access free ART in the government treatment program.
From October 2013 to November 2015, a Baseline Household Survey of approximately 20% of randomly selected households was conducted in all 30 study communities. Survey participants were residents of these households, aged 16-64 years, who were Botswana citizens or spouses of citizens, and who gave consent. From those household participants, a longitudinal cohort was established.
People in the cohort were visited annually. HIV-negative individuals were tracked for incidence. HIV-positive individuals were tracked for linkage to care (referring person to clinic, making sure person shows up for initial appointment and receives treatment).
At the end of the study, we compared the number of new HIV infections in the 15 intervention communities with the 15 standard-of-care communities. We also compared ART use and HIV viral load levels across community pairs.
Study Population and Size: Average Community Population of 6,000, Total Population -180,800 (nearly 10% of the entire Botswana Population). Age Eligible (16-64) -105,000
Study Duration: Approximately 48 months.
Sponsor: U.S. Centers for Disease Control –CDC (via President’s Emergency Plan for AIDS Relief, PEPFAR).
HIV Incidence
Results from the Ya Tsie study showed a 31% decrease in the rate of new HIV infections in the intervention communities compared with the standard-of-care communities, over a total period of only 29 months (Makhema et al. 2019). The actual impact of the interventions was undoubtedly greater, taking into account the fact that mobility to and from the intervention communities diluted the effect of the intervention on lowering the rate of new HIV infections. Women, particularly young women, were at significantly greater risk for HIV acquisition than men, even in the intervention communities (Makhema et al. 2019; Ussery et al. 2020).
Uptake of Interventions
Population levels of HIV treatment and viral suppression increased in all communities during the study period. However, significantly larger increases in coverage were observed in the intervention communities. By study end, 88% of PLWH in the intervention communities were virally suppressed on ART (Makhema et al. 2019; Wirth et al. 2020). This is one of the highest population levels of viral suppression described to date and exceeds the UNAIDS target goal.
Our findings demonstrate that it is possible to further increase uptake of intervention services in a relatively short period of time in a high-prevalence generalized epidemic. Findings also suggest that sustaining high coverage ART levels over time may further reduce HIV incidence.
Study results showed that uptake of HIV testing and treatment was not uniform across age and sex. Females of all ages were more likely to be tested, know their HIV status, and initiate treatment compared to their male counterparts (Wirth et al. 2020).
Younger people and males had poorer ART uptake and were also less likely to achieve viral suppression. However, importantly, the increases over time in viral suppression among PLWH were even greater for men than for women, and for youth as compared to older persons, in Ya Tsie (Lebelonyane et al. 2019).
In addition, once initiated on ART, males and females perform equally well with regards to viral suppression. Our findings also provide evidence that it is indeed possible to reach men and younger persons with HIV testing and treatment interventions using more targeted and friendly approaches.
The uptake of Safe Male Circumcision during the study was low in all communities, especially in communities in the central and north of the country. By study end, 54% of eligible men in intervention communities and 42% of eligible men in standard-of-care communities reported being circumcised, an increase of 15% and 10%, respectively, from baseline levels (Wirth et al. 2020).
Intervention Delivery
In the intervention arm, the time to ART start was significantly shorter (Makhema et al. 2019). Community HIV testing (home-based plus mobile) and rapid ART initiation (at first clinic visit) were key to achieving this. Rapid ART start was safe and highly acceptable to patients. Compared to traditional ART start approaches (after multiple visits and safety labs with long delays), rapid ART start resulted in much faster ART initiation and equally high retention and viral suppression rates (Lebelonyane et al. 2020).
Active linkage to care worked well. Although most people showed up at a clinic for ART initiation at the first given appointment with a brief SMS reminder, following up on persons who did not show up led to substantial increases in timely ART start (Alwano et al. 2017). Approximately 15% of persons starting ART did so in a community that was not their community of residence (Bachanas et al. 2018).
A data system which enabled staff to track individual patients through the care cascade, from HIV testing through clinic/ART linkage and subsequent treatment retention, was an essential element of success.
