Introduction The WHO recommends antiretroviral treatment (ART) for all HIV-positive patients regardless of CD4 count or disease stage, referred to as "Early Access to ART for All" (EAAA). The... Show moreIntroduction The WHO recommends antiretroviral treatment (ART) for all HIV-positive patients regardless of CD4 count or disease stage, referred to as "Early Access to ART for All" (EAAA). The health systems effects of EAAA implementation are unknown. This trial was implemented in a government-managed public health system with the aim to examine the "real world" impact of EAAA on care retention and viral suppression. Methods In this stepped-wedge randomized controlled trial, 14 public sector health facilities in Eswatini were paired and randomly assigned to stepwise transition from standard of care (SoC) to EAAA. ART-naive participants >= 18 years who were not pregnant or breastfeeding were eligible for enrolment. We used Cox proportional hazard models with censoring at clinic transition to estimate the effects of EAAA on retention in care and retention and viral suppression combined. Results Between September 2014 and August 2017, 3405 participants were enrolled. In SoC and EAAA respectively, 12-month HIV care retention rates were 80% (95% CI: 77 to 83) and 86% (95% CI: 83 to 88). The 12-month combined retention and viral suppression endpoint rates were 44% (95% CI: 40 to 48) under SoC compared to 80% (95% CI: 77 to 83) under EAAA. EAAA increased both retention (HR: 1 center dot 60, 95% CI: 1 center dot 15 to 2 center dot 21,p = 0.005) and retention and viral suppression combined (HR: 4.88, 95% CI: 2.96 to 8.05,p < 0.001). We also identified significant gaps in current health systems ability to provide viral load (VL) monitoring with 80% participants in SoC and 66% in EAAA having a missing VL at last contact. Conclusions The observed improvement in retention in care and on the combined retention and viral suppression provides an important co-benefit of EAAA to HIV-positive adults themselves, at least in the short term. Our results from this "real world" health systems trial strongly support EAAA for Eswatini and countries with similar HIV epidemics and health systems. VL monitoring needs to be scaled up for appropriate care management. Show less
Introduction Globally, schistosomes infect approximately 200 million people, with 90% of infections in sub-Saharan Africa. Schistosomiasis is hypothesized to increase HIV-1 acquisition risk, and... Show moreIntroduction Globally, schistosomes infect approximately 200 million people, with 90% of infections in sub-Saharan Africa. Schistosomiasis is hypothesized to increase HIV-1 acquisition risk, and multiple cross-sectional studies reported strong associations. We evaluated this hypothesis within four large prospective cohorts. Methods We conducted nested case-control analyses within three longitudinal cohorts of heterosexual HIV-1 serodiscordant couples and one female sex worker (FSW) cohort from Kenya and Uganda. The serodiscordant couples studies were conducted between 2004 and 2012 while the FSW cohort analysis included participant follow-up from 1993 to 2014. Cases HIV-1 seroconverted during prospective follow-up; three controls were selected per case. The presence of circulating anodic antigen in archived serum, collected prior to HIV-1 seroconversion, identified participants with active schistosomiasis; immunoblots determined the schistosome species. Data from serodiscordant couples cohorts were pooled, while the FSW cohort was analysed separately to permit appropriate confounder adjustment. Results We included 245 HIV-1 seroconverters and 713 controls from the serodiscordant couples cohorts and 330 HIV-1 seroconverters and 962 controls from the FSW cohort. The prevalence of active schistosomiasis was 20% among serodiscordant couples and 22% among FSWs. We found no association between schistosomiasis and HIV-1 acquisition risk among males (adjusted odds ratio (aOR) = 0.99, 95% CI 0.59 to 1.67) or females (aOR = 1.21, 95% CI 0.64 to 2.30) in serodiscordant couples. Similarly, in the FSW cohort we detected no association (adjusted incidence rate ratio (aIRR) = 1.11, 95% CI 0.83 to 1.50). Exploring schistosome species-specific effects, there was no statistically significant association between HIV-1 acquisition risk andSchistosoma mansoni(serodiscordant couples: aOR = 0.90, 95% CI 0.56 to 1.44; FSW: aIRR = 0.83, 95% CI 0.53 to 1.20) orSchistosoma haematobium(serodiscordant couples: aOR = 1.06, 95% CI 0.46 to 2.40; FSW: aIRR = 1.64, 95% CI 0.93 to 2.87) infection. Conclusions Schistosomiasis was not a strong risk factor for HIV-1 acquisition in these four prospective studies.S. mansoniwas responsible for the majority of schistosomiasis in these cohorts, and our results do not support the hypothesis thatS. mansoniinfection is associated with increased HIV-1 acquisition risk.S. haematobiuminfection was associated with a point estimate of elevated HIV-1 risk in the FSW cohort that was not statistically significant, and there was no trend towards a positive association in the serodiscordant couples cohorts. Show less