Africa Health Research Institute

The HIV-1 pandemic is characterized by extensive viral genetic diversity, with strains that can be classified into distinct clades or subtypes based on sequence relatedness. Biological differences between subtypes have also been reported. HIV-1 subtype B, predominant in North America and Europe is most studied, but non-B subtypes represent the majority of infections globally and in sub-Saharan Africa, which accounts for more than two-thirds of people living with HIV. Whereas the implications of genetic and biological diversity overall for HIV prevention, treatment and cure strategies are recognized, the impact of clade differences is contested. Here we review how viral and host diversity, including subtype-specific differences may shape HIV pathogenesis, reservoir characteristics and cure strategies, highlighting data from regions where non-B subtypes circulate. Studies from African and global cohorts highlight differences in epidemiological spread and disease progression among HIV-1 subtypes that may be attributed to viral genetic sequence variations and resultant distinct properties in viral replication capacity, immune evasion, interferon resistance, co-receptor usage, latency regulation and reservoir biology. HIV-1 diversity has implications for virus biology, transmission and clinical outcomes. Clade-specific differences therefore warrant consideration in the development and design of prevention, treatment and cure strategies, including diagnostic and monitoring assays. Incorporating multi-clade research and regionally relevant cohorts will advance and accelerate efforts toward a universally applicable HIV cure.

Abstract Background Reductions in United States (US) funding for tuberculosis (TB) and HIV programmes have raised concerns and challenges for TB care and management in South Africa and globally. We used mathematical modelling to illustrate the potential impact of unmitigated funding disruptions, estimating long-term effects on TB incidence and mortality over 2025–2035. Methods Stakeholder-informed scenarios were modelled, assuming both minimal and maximal disruptions to key TB and HIV services, including preventive therapy for people living with HIV (PLHIV), TB testing, TB treatment initiation, and antiretroviral therapy (ART) coverage. Results and discussion Between 2025 and 2035, reduced ART coverage was projected to result in 235,000–1,000,000 additional HIV infections; and a 12–41% increase in TB episodes, and 21–72% rise in TB deaths among people living with HIV. Overall, 220,000–730,000 additional TB episodes and 67,000–225,000 TB deaths are anticipated, potentially reversing years of progress. Although mitigation efforts were not included in the model, early responses in South Africa have involved increased diagnostic testing and additional domestic funding. To maintain progress in TB and HIV control, rapid and sustained programmatic responses and funding are essential to prevent substantial setbacks and avert avoidable illness and death.

Limited male engagement in HIV prevention and care is a global challenge more pronounced in sub-Saharan Africa (SSA) contributing to ongoing transmission. However, peer network interventions show promise in improving engagement. To map and synthesise evidence on peer network interventions for HIV prevention and care among men in SSA, with a focus on the types of strategies used, populations reached and how these interventions address cultural, social and structural barriers across the HIV care cascade. Scoping review of peer-reviewed literature, conducted and reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. Community and facility-based HIV prevention and care settings across multiple countries in SSA. Populations included men having sex with men, men in key occupational groups (fishermen, truck drivers), adolescents and young people, and men living with HIV. Studies not conducted in SSA, not peer-reviewed or not focused on male peer networks were excluded. Peer network interventions included peer education, peer navigation, HIV self-testing (HIVST) distribution, adherence support groups, disclosure and stigma-reduction counselling, technology-enabled peer support (SMS and social media) and community-based antiretroviral therapy (ART) delivery. Intervention duration and intensity varied across studies. Primary outcomes included HIV testing uptake, linkage to care, ART initiation, adherence, retention in care and viral suppression. Secondary outcomes included stigma reduction, disclosure and engagement among hard-to-reach male populations. We conducted a review of literature published between November 2013 and November 2024, searching PubMed, Web of Science, Scopus and Cochrane databases. Studies were included if they examined peer network approaches in HIV prevention and care among men in SSA. A total of 905 records were identified, of which 75 studies met the inclusion criteria. Peer network interventions were implemented across diverse SSA contexts and male populations. Strategies such as peer-led education, social diffusion models, HIVST distribution and technology-enabled peer support consistently improved HIV testing uptake, linkage to care, ART initiation and adherence. Contextually tailored interventions such as community-based outreach addressing occupational risk environments and economic vulnerabilities were particularly effective in engaging men traditionally underserved by facility-based services. However, challenges persisted, including variable linkage to care following HIVST and sensitivity to user costs. Peer-led interventions in HIV care for men in SSA effectively address cultural, social and structural barriers, improving testing, ART adherence and viral suppression. Tailored, technology-enhanced and community-based approaches ensure equitable HIV prevention and treatment outcomes, despite challenges like linkage to care.

Background/Objectives: The overuse and misuse of antibiotics contribute to antimicrobial resistance (AMR) globally. The appropriateness of antibiotic prescribing at the primary healthcare (PHC) level must be urgently addressed to reduce high levels of inappropriate antibiotic prescribing and associated AMR. This study aimed to develop quality indicators, based on the World Health Organization (WHO)'s Access, Watch, Reserve (AWaRe) guidance, to assess the appropriateness and quality regarding antibiotic prescribing in public PHC settings in South Africa. Methods: Potential indicators were identified from indicators developed by City St George's, University of London (SGUL); a review of AWaRe-based indicators; and the results from point prevalence surveys at PHC clinics in South Africa. The indicators were developed using the RAND/UCLA Appropriateness Method. In Round 1, 12 experts individually rated 78 indicators for clarity and appropriateness. In Round 2, 10 experts rated 89 indicators for appropriateness and feasibility during an interactive online meeting. Results: The final set had 61/89 indicators (68.5%) that were rated both appropriate and feasible with agreement. Dental infections (9/9; 100%) alongside skin and soft tissue infections (11/13; 84.6%) had the highest percentage of indicators that were rated appropriate and feasible with agreement. Lower urinary tract infections (6/11; 54.5%) and general (4/8; 50%) categories had the lowest percentage of indicators rated appropriate and feasible with agreement. Conclusions: The process proved valuable in developing potential indicators for use in future antimicrobial stewardship programmes to improve antibiotic prescribing in public sector PHC facilities in South Africa and beyond.

Background: Hemorrhagic stroke remains a major contributor to neurological morbidity and mortality, particularly in low- and middle-income countries where timely and coordinated care is critical. Nurses play a central role in the assessment, monitoring, and prevention of secondary complications in patients with hemorrhagic stroke; however, evidence on their knowledge and practices in resource-limited settings is limited. Objective: This study assessed nurses’ knowledge and clinical practices and examined their influence on the management of patients with hemorrhagic stroke at Kabgayi Hospital, Rwanda. Methods: A descriptive cross-sectional design was conducted among 87 registered nurses working in medical and intensive care units. Stratified random sampling was applied. Data were collected using a validated self-administered questionnaire to assess knowledge, practices, and management of hemorrhagic stroke. Descriptive statistics summarized variable levels, while Spearman’s rho correlation coefficient was used to examine relationships between knowledge, practices, and patient management. Statistical analysis was performed using SPSS version 25, with significance set at p < 0.05. Results: Nurses demonstrated a high level of hemorrhagic stroke management (mean = 4.11, SD = 0.67), particularly in complication prevention and multidisciplinary collaboration. Knowledge levels were high (mean = 4.03, SD = 0.65), although gaps were identified in stroke pathophysiology. Clinical practices were also rated high (mean = 4.03, SD = 0.65), with documentation scoring highest and timely neurological assessments scoring comparatively lower. A moderate positive correlation was observed between nurses’ knowledge and patient management (ρ = 0.509, p < 0.001), while nurses’ practices showed a very strong positive correlation with patient management (ρ = 1.000, p < 0.001). Conclusion: Hemorrhagic stroke management at Kabgayi Hospital is predominantly driven by nurses’ clinical practices, supported by adequate knowledge. Strengthening practice-focused training, institutional support, and multidisciplinary stroke care is essential to optimize patient outcomes in resource-constrained healthcare settings.

Acute pancreatitis (AP) varies in severity, and traditional severity stratifications often fail to predict its early course. In people living with HIV (PLWH), chronic immune dysregulation leads to aberrant cytokine responses which influence biomarker performance. We hypothesize that in regions with high prevalence of HIV infection, HIV status will influence the immune biomarker performance in the prediction of severity of AP. In this prospective case-control study conducted in KwaZulu-Natal, 144 adult patients with AP (29 % PLWH) were enrolled. Blood samples were collected within 24 h of admission, and plasma was isolated and cryopreserved before cytokine levels were quantified using a multiplex electrochemiluminescence assay. Clinical severity was assessed using revised Atlanta classification. Receiver operating characteristic analyses were performed to derive optimal biomarker thresholds based on Youden's index, with significance set at p < 0.01. In people without HIV, IL-6, TNF-α, IL-15, IL-17, and MCP-1 were significantly upregulated in severe AP, with IL-15 demonstrating the highest discriminative performance (AUC 0.917; optimal cut-off 3.79 pg/mL; sensitivity 94.1 %, specificity 72.9 %). In PLWH patients, TNF-α was the only cytokine significantly associated with AP severity (AUC 0.974; optimal cut-off 9.42 pg/mL; sensitivity 100 %, specificity 97.4 %), while IL-17 did not predict severity in PLWH. Across the combined cohort, cytokine thresholds were higher in PLWH. Distinct immune signatures correlate with AP severity and are significantly influenced by HIV status. IL-15 outperformed IL-6, TNF-α, IL-17, and MCP-1 in people without HIV, whereas TNF-α was the only predictor of severity in PLWH. Higher thresholds for prediction of severity in PLWH underscore the need for HIV-specific biomarker thresholds and further research into tailored severity stratification, and development of immunomodulating therapies in AP.

Objective: Women aged 40–65 years, who undergo predictable and important physiological transitions, feel that access in England to Women’s Health and Wellbeing Services (WHWS) is poor and inequitable. The barriers and enablers to WHWS, focusing on sexual health and sexual wellbeing services, for women aged 40–65 years, and feasible suggestions for development, were explored from the perspective of 11 providers of health and social care. Design: A qualitative study, using semi-structured interviews, was conducted with providers of WHWS. Framework Analysis, applying the Socio-ecological Model (SEM), through an intersectionality lens, was employed to analyse the findings. The study was reported according to the Consolidated Criteria for Reporting Qualitative Research (COREQ). Setting and Participants: Eleven providers of care were recruited by convenience sampling from health and wellbeing settings serving the most under-resourced areas in South-East England. Results: The intersectional disadvantage of belonging to underserved groups overlapped across the constructs of the SEM. The main themes that emerged were the lack of prioritisation of midlife women within society, and the inadequate knowledge about the health and well-being requirements, including the sexual health and sexual well-being requirements, of midlife women. Conclusion: Amongst policy makers, the sensitive, complex, and interlinked nature of health and wellbeing, including sexual health and sexual wellbeing, of midlife women must be recognised. Investment in public and Health Care Professionals’ education, together with a life-course approach to health research and policy, is required to destigmatise and improve access to WHWS for midlife women.

Repeating an intervention strategy consistent with the chronic disease care model has been demonstrated to be efficacious in improving cessation outcomes among smokers. However, evidence is lacking for repeat treatment outcomes among people with HIV (PWH) who smoke in low-resource settings. We evaluated outcomes among participants (n = 384) who were provided a second round of treatment after initial treatment failure in a randomized controlled trial of behavioral counseling (BC) with or without combination nicotine replacement therapy (nicotine patches and gum, cNRT). The primary outcome was self-reported smoking abstinence at 6 months after repeat treatment, biochemically verified using exhaled breath carbon monoxide (CO) and urine cotinine test. Secondary outcomes include smoking abstinence at 2 months after repeat treatment and smoking reduction, measured by changes in exhaled breath CO at 2 months and 6 months after repeat treatment. Overall, 35 (9%) participants were abstinent at 6 months post-repeat treatment, including 15 (8%) participants in the repeat BC group compared to 20 (11%) participants in the repeat BC + cNRT group. There was no significant difference in abstinence rates between repeat treatment groups (Chi Squared (χ2) = 0.23; p = 0.63), including after adjusting for potential confounders [adjusted risk ratio (aRR) = 1.16, 95% CI 0.39, 3.47; p = 0.79]. Although augmenting repeat treatment of BC with cNRT may not provide additional benefits for PWH with prior treatment failure in this population, PWH in this setting may benefit from a repeat treatment strategy of BC with or without cNRT.

Abstract Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains the leading cause of death from infection globally, yet the contribution of non-classical T-cell pathways to human immunity remains poorly defined. CD1c-autoreactive T-cells, which recognise self-lipids presented by the antigen-presenting molecule CD1c, are frequent in human blood, but their role during infection is unclear. Here, we investigate how CD1c-expressing antigen-presenting cells (APCs) and Mtb infection shape CD1c-autoreactive T-cell responses using engineered human APC systems, complemented by single-cell transcriptomic profiling to define the ex vivo phenotypic landscape of these T-cells. CD1c is present within human TB granulomas, whereas Mtb down-modulates CD1c expression on infected APCs, consistent with an immune evasion strategy. CD1c-autoreactive T-cells respond more strongly to Mtb-infected CD1c+ APCs than to uninfected cells, exhibiting enhanced activation, cytotoxicity, and diverse cytokine secretion via CD1c-dependent recognition. Under in vitro conditions, these T-cells reduce relative Mtb burden in infected phagocytes. Single-cell RNA-sequencing reveals cytotoxic effector-memory programmes and expression of antimicrobial molecules, providing a mechanistic basis for these responses. Together, these findings define a human CD1c-restricted T-cell response to Mtb-infected APCs and identify autoreactive CD1c-restricted T-cells as a candidate cellular axis for lipid-directed immunity in TB.

In South Africa, gender-based violence (GBV) is a public health crisis contributing to the transmission of HIV and requiring urgent intervention. Using mixed methods, this study evaluated the relationship between adolescents' attitudes toward GBV and their sexual behaviors. Adolescent girls and young women (AGYW) and adolescent boys and young men (ABYM) completed a questionnaire assessing socio-demographic characteristics, sexual risk behavior, and attitudes regarding GBV. Two focus group discussions (FGDs) were conducted to explore perceptions of GBV. Among 178 participants, 80 (44.9%) had permissive attitudes toward GBV. Being AGYW and in a relationship were associated with permissive GBV attitudes. FGDs revealed that participants perceive GBV as occurring both in society and communities, as well as within interpersonal relationships at home. This violence is perpetuated by enduring patriarchal beliefs, male authority, and economic inequalities. Effective prevention of GBV requires integrated, multi-level strategies addressing patriarchal norms, economic inequalities through contextually tailored interventions at home and throughout society.