RESULTS OF THE SAPPHIRE TRIAL : A CLUSTER RANDOMISED TRIAL OF A COMPREHENSIVE TARGETTED COMBINATION PREVENTION INTERVENTION TO SUPPORT FEMALE SEX WORKERS IN ZIMBABWE TO LINK AND ADHERE TO ANTIRETROVIRALS FOR TREATMENT AND PREVENTION

WORD COUNT 259, MAX 250) BACKGROUND Strengthening female sex workers’ (FSW) engagement with services is needed to eliminate HIV. We aimed to determine the impact of a targeted combination intervention for FSW in Zimbabwe. METHODS We conducted a cluster-randomised trial between 2014-2016 randomising 14 clusters (areas surrounding FSW clinics) in matched pairs to usual-care (free sexual-health services supported by peer educators, including HIV testing on demand, referral for antiretroviral therapy (ART), and health education) or enhanced-intervention arms (regular HIV testing, on-site ART and pre-exposure prophylaxis; adherence support, and intensified community mobilization). Primary outcome: proportion of all FSW with HIV viral load (VL) >=1,000 copies per mL, assessed through respondent driven sampling surveys. We used an adapted cluster-summary approach to estimate risk differences. RESULTS At intervention sites, 4,619 FSW attended clinics compared to 3,612 in comparison sites, twice as many were tested (2,606 vs 1,151) and diagnosed HIV positive (1,052 vs 546). The proportion of all FSW with VL >=1,000 copies per mL fell in both arms, (29.5% (407/1317) to 19.1% (272/1397) in usual-care and 30.2% (384/1259) to 16.4% (232/1393) in enhanced intervention arm) but with a risk difference of only 2.8% (95% CI: -8.1%, 2.5%) at endline, p-value=0.23. Among HIV-positive women, the proportions with VL<1000 copies per mL rose to 72.0% (562/794) in the enhanced-intervention and 67.5% (569/841) in the usual-care arm, adjusted risk difference of 5.3% (95% CI: -4.0%, 14.6%), p-value=0.20. There were no adverse events. INTERPRETATION Within a dedicated FSW programme, high levels of HIV diagnosis and treatment are achievable. Further research is required to optimise programme content and intensity for population impact. FUNDING The Sisters Antiretroviral therapy Programme for Prevention of HIV: an Integrated Response (SAPPH-IRe) trial was funded by United Population Population Fund (UNFPA) via Zimbabwe’s Integrated Support Fund which received funds from DfID, Irish Aid and SIDA. A small amount of funding for survey work is from GIZ. USAID supported the cost of PSI Zimbabwe to deliver ART and PrEP to sex workers as part of the trial. We received a donation of Truvada for PrEP use for the trial from Gilead Sciences. INTRODUCTION Worldwide, female sex workers have approximately 13.5-times higher odds of HIV infection than women in the general population1. Many have reduced access to testing and treatment, and face barriers to adherence1,2. In Zimbabwe, analysis of data from 2009-2013 found HIV incidence among female sex workers to be over 10 new cases per 100 person-years at risk3. Only 67% were aware of their HIV status, while less than 50% living with HIV had an undetectable viral load, defined as <1000 copies per mL4. Consistent condom use with clients was reported by 65-73%. Heterosexual transmission of HIV is unlikely to occur with viral load of <1500 copies per mL5. Modelling suggests that over 40% of new infections among the general population are attributable to unsafe sex work, because of both high HIV incidence and high prevalence of infectious HIV among this group, leading to transmission to others6. While guidelines for interventions for female sex workers exist7, few evaluations have assessed impact on engagement with HIV prevention and care, particularly in Africa and since the preventative effects of ART and efficacy of oral pre-exposure prophylaxis (PrEP) have become clear8 Reducing the burden of infectious HIV among female sex workers requires interventions that strengthen demand, enhance supply, and support optimal use of any prevention or treatment strategy adopted. Demand-side interventions should increase risk perception, support positive attitudes towards HIV prevention and treatment, foster positive social norms, and build social cohesion to enhance risk reduction. Supply-side interventions should increase accessibility and availability of HIV-testing and treatment, and of HIV prevention tools such as condoms, contraception, and PrEP. For adherence, interventions should support behavioural self-efficacy and skills9. Based on these principles, we enhanced the existing Sisters programme to develop the Sisters Antiretroviral Prevention Programme – an Integrated Response (SAPPH-IRe) combination-HIV-prevention-and-treatment-intervention package, and evaluated its impact on the proportion of all female sex workers with an HIV viral load >=1000 copies per mL in a cluster-randomised trial in Zimbabwe (see Theory of Change Webappendix 2 page 4). Our hypothesis was that the targeted and dedicated delivery and support of our enhanced intervention would reduce the proportion of female sex workers living with an HIV viral load >=1000 copies per mL when compared with the current WHO-guideline-based usual care.