Summary Background In Africa, up to 30% of HIV-infected patients who are clinically eligible for antiretroviral therapy (ART) do not start timely treatment. We assessed the effects of an intervention targeting prevalent health systems barriers to ART initiation on timing and completeness of treatment initiation. Methods In this stepped-wedge, non-blinded, cluster-randomised controlled trial, 20 clinics in southwestern Uganda were randomly assigned in groups of five clinics every 6 months to the intervention by a computerised random number generator. This procedure continued until all clinics had crossed over from control (standard of care) to the intervention, which consisted of opinion-leader-led training and coaching of front-line health workers, a point-of-care CD4 cell count testing platform, a revised counselling approach without mandatory multiple pre-initiation sessions, and feedback to the facilities on their ART initiation rates and how they compared with other facilities. Treatment-naive, HIV-infected adults (aged ≥18 years) who were clinically eligible for ART during the study period were included in the study population. The primary outcome was ART initiation 14 days after first clinical eligibility for ART. This study is registered with ClinicalTrials.gov, number NCT01810289. Findings Between April 11, 2013, and Feb 2, 2015, 12 024 eligible patients visited one of the 20 participating clinics. Median CD4 count was 310 cells per μL (IQR 179–424). 3753 of 4747 patients (weighted proportion 80%) in the intervention group had started ART by 2 weeks after eligibility compared with 2585 of 7066 patients (38%) in the control group (risk difference 41·9%, 95% CI 40·1–43·8). Vital status was ascertained in a random sample of 208 patients in the intervention group and 199 patients in the control group. Four deaths (2%) occurred in the intervention group and five (3%) occurred in the control group. Interpretation A multicomponent intervention targeting health-care worker behaviour increased the probability of ART initiation 14 days after eligibility. This intervention consists of widely accessible components and has been tested in a real-world setting, and is therefore well positioned for use at scale. Funding National Institute of Allergy and Infectious Diseases (NIAID) and the President’s Emergency Fund for AIDS Relief (PEPFAR).

No abstract

IntroductionThe success of universal antiretroviral therapy (ART) access and aspirations for an AIDS‐free generation depend on high adherence in individuals initiating ART during early‐stage HIV infection; however, adherence may be difficult in the absence of illness and associated support.MethodsFrom March 2015 to October 2017, we prospectively observed three groups initiating ART in routine care in Uganda and South Africa: men and non‐pregnant women with early‐stage HIV infection (CD4 > 350 cells/μL), pregnant women with early‐stage HIV infection and men and non‐pregnant women with late‐stage HIV infection (CD4 < 200 cells/μL). Socio‐behavioural questionnaires were administered and viral loads were performed at 0, 6 and 12 months. Adherence was monitored electronically.ResultsAdherence data were available for 869 participants: 322 (37%) early/non‐pregnant, 199 (23%) early/pregnant and 348 (40%) late/non‐pregnant participants. In Uganda, median adherence was 89% (interquartile range 74 to 96) and viral suppression was 90% at 12 months; neither differed among groups (p > 0.72). In South Africa, median adherence was higher in early/non‐pregnant versus early/pregnant or late/non‐pregnant participants (76%, 37%, 52%; p < 0.001), with similar trends in viral suppression (86%, 51%, 79%; p < 0.001). Among early/non‐pregnant individuals in Uganda, adherence was higher with increasing age and lower with structural barriers; whereas in South Africa, adherence was higher with regular income, higher perceived stigma and use of other medications, but lower with maladaptive coping and cigarette smoking.DiscussionART adherence among non‐pregnant individuals with early‐stage infection is as high or higher than with late‐stage initiation, supporting universal access to ART. Challenges remain for some pregnant women and individuals with late‐stage infection in South Africa and highlight the need for differentiated care delivery.

Background HIV antiretroviral therapy (ART) is being rapidly scaled up in Sub-Saharan Africa, including recently to patients with CD4+ T-cell counts >350 cells/uL. However, concerns persist about adherence and virologic suppression among these asymptomatic, high CD4+ count individuals. Objective To determine the virologic efficacy and safety of ART among asymptomatic HIV-positive Ugandan adults with high CD4+ counts ≥350 cells/uL via a streamlined model of care. Design Prospective non-randomized clinical study (EARLI Study: clinicaltrials.gov NCT#01479634). Setting Prototypic rural Ugandan HIV clinic. Subjects/Participants N=197 asymptomatic ART-naïve adults (age>18) with CD4+ ≥350, without pregnancy or WHO stage 3/4 illness. Interventions ART included tenofovir/emtricitabine/efavirenz, with ritonavir/lopinavir substitution for efavirenz available. Streamlined ART model included nurse-driven visits with physician backup, basic safety laboratory monitoring with HIV viral load (VL), clinician telephone contact, and defaulter tracking. No incentives were provided. Outcomes Undetectable VL (≤400 copies/mL) at 24 and 48 weeks (intention-to-treat [ITT]; missing=detectable), self-reported ART adherence, retention in care, and laboratory/clinical ART toxicities. Results Of 197 patients with CD4>350, median CD4 was 569 (IQR 451-716). Undetectable VL was achieved in 189/197 (95.9%, ITT) and 189/195 (96.9%, ITT) of participants at weeks 24 and 48, respectively. Self-reported adherence was 98% and 192/197 (97%) of patients were retained at week 48. Laboratory adverse events and hospitalizations were rare. Conclusions We demonstrate high virologic suppression, retention, and safety among asymptomatic individuals with CD4>350 in a prototypic Ugandan clinic. Our results challenge current concerns that high CD4+ count individuals lack motivation for ART, and may not achieve sustained virologic suppression.