Objectives: Viral suppression (VS) is the hallmark of successful antiretroviral therapy (ART) programmes. We sought to compare clinic retention, virological outcomes, drug resistance and mortality between peri-urban and rural settings in South Africa after first-line ART. Methods: Beginning in July 2014, 1000 (500 peri-urban and 500 rural) ART-naïve patients with HIV were enrolled and managed according to local standard of care. Clinic retention, virological suppression, virological failure (VF), genotypic drug resistance and mortality were assessed. The definition of VS was a viral load ≤1000 copies/ml. Time to event analyses were stratified by site, median age and gender. Kaplan–Meier curves were calculated and graphed with log-rank modelling to compare curves. Results: Based on 2741 patient-years of follow-up, retention and mortality did not differ between sites. Among all 1000 participants, 47%, 84% and 91% had achieved VS by 6, 12 and 24 months, respectively, which was observed earlier in the peri-urban site. At both sites, men aged < 32 years had the highest proportion of VF (15.5%), while women aged > 32 years had the lowest, at 7.1% (p = 0.018). Among 55 genotypes, 42 (76.4%) had at one or more resistance mutations, 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%). Conclusions: No significant differences in treatment outcomes between peri-urban and rural clinics were observed. In both settings, young men were especially susceptible to clinic attrition and VF. More effective adherence support for this important demographic group is needed to achieve UNAIDS targets.

Background: The essential components of a vaccine delivery system are well-documented, but robust evidence is lacking on how policies and implementation strategies are operationalized to drive catalytic improvements in coverage. To address this gap, we identified success factors that supported improvements in routine immunization coverage in Senegal, especially from 2000 to 2019. Methods: We identified Senegal as an exemplar in the delivery of childhood vaccines through analysis of DTP1 and DTP3 coverage data. Through interviews and focus group discussions at the national, regional, district, health facility, and community-level, we investigated factors that contributed to high and sustained vaccination coverage. We conducted a thematic analysis through application of implementation science frameworks to determine critical success factors. We triangulated these findings with quantitative analyses using publicly available data. Results: The following success factors emerged: 1) Strong political will and prioritization of resources for immunization programming supported urgent allocation of funding and supplies; 2) Collaboration between the Ministry of Health and Social Action and external partners fostered innovation, capacity building, and efficiency; 3) Improved surveillance, monitoring, and evaluation allowed for timely and evidence-based decision making; 4) Community ownership of vaccine service delivery supported tailored programming and response to local needs; and 5) Community health workers spearheaded vaccine promotion and demand generation for vaccines. Conclusion: The vaccination program in Senegal was supported by evidence-based decision making at the national-level, alignment of priorities between governmental entities and external partners, and strong community engagement initiatives that fostered local ownership of vaccine delivery and uptake. High routine immunization coverage was likely driven by prioritization of immunization programming, improved surveillance systems, a mature and reliable community health worker program, and tailored strategies for addressing geographical, social, and cultural barriers.

Genome-wide association studies (GWAS) of circulating metabolites have revealed the role of genetic regulation on the human metabolome. Most previous investigations focused on European ancestry, and few studies have been conducted among populations of African descent living in Africa, where the infectious disease burden is high (e.g., human immunodeficiency virus (HIV)). It is important to understand the genetic associations of the metabolome in diverse at-risk populations including people with HIV (PWH) living in Africa. After a thorough literature review, the reported significant gene–metabolite associations were tested among 490 PWH in South Africa. Linear regression was used to test associations between the candidate metabolites and genetic variants. GWAS of 154 plasma metabolites were performed to identify novel genetic associations. Among the 29 gene–metabolite associations identified in the literature, we replicated 10 in South Africans with HIV. The UGT1A cluster was associated with plasma levels of biliverdin and bilirubin; SLC16A9 and CPS1 were associated with carnitine and creatine, respectively. We also identified 22 genetic associations with metabolites using a genome-wide significance threshold (p-value < 5 × 10−8). In a GWAS of plasma metabolites in South African PWH, we replicated reported genetic associations across ancestries, and identified novel genetic associations using a metabolomics approach.