Comparing Effectiveness of First-Line Antiretroviral Therapy between Peri-Urban and Rural Clinics in KwaZulu-Natal, South Africa

Background: Viral suppression (VS) is the hallmark of successful antiretroviral therapy (ART) programs. We sought to compare clinic retention, virologic outcomes, drug resistance, and mortality between peri-urban and rural settings in South Africa after first-line ART. Methods: ADReSS was a prospective study where 1,000 ART-naive people with HIV were enrolled, 500 at each site (one urban and one rural), between July 2014 and September 2016 and observed until July 2018. Participants were managed per local standard of care. Endpoints assessed included clinic retention, virologic suppression (VS), virologic failure (VF), genotypic drug resistance, and mortality. VS was defined as a viral load (VL) £1000 copies/mL. Time to event analyses were stratified (by site, median age, and gender). Kaplan-Meier (KM) curves were calculated and graphed with log-rank modelling to compare curves. Findings: Based on 2,741 patient-years of follow-up, retention and mortality did not differ between sites. Among all 1,000 participants, 73·9%, 83·9%, and 87·7% had achieved VS by six, 12, and 24 months, respectively, which was observed earlier in the peri-urban site.  At both sites, men 32 years had the lowest with just 7·1% (p=0·018). Of all participants achieving VS, only 63 (8·7%) subsequently developed VF. This  rate did not differ by site but was greater for men <32 years at both sites (p=0·015). Among 55 genotypes, 42 (76·4%) had at least one resistance mutation which did not differ by site. K103N (59%) and M184V (52%) were the most common mutations, followed by V106M and K65R (31% each). Overall, death was infrequent (<4%). Interpretation: No significant differences in treatment outcomes between urban and rural sites were observed. In both settings, young men were especially vulnerable to clinic attrition and VF. More effective adherence support for this important demographic group is needed to achieve UNAIDS targets. Funding Information: National Institute of Allergy and Infectious Diseases of the National Institutes of Heath and Emory CFAR.    Declaration of Interests: V.C.M. has received investigator-initiated research grants (to the institution) and consultation fees (both unrelated to the current work) from Eli Lilly, Bayer, Gilead Sciences and ViiV. D.R.K. has received consulting honoraria (unrelated to the current work) and/or research grants (to the institution) from Gilead, GlaxoSmithKline, Merck and ViiV. MYS received consulting fees unrelated to the current work from MSD, J&J, CIPLA, and Gilead. All other authors report no potential conflicts. Ethics Approval Statement: Ethics approval from the Biomedical Research Ethics Committee of the University of KwaZulu-Natal, the Emory University and Mass General Brigham Institutional Review Boards was obtained prior to the start of the study. Signed informed consent was obtained.