Uganda Genome Resource Enables Insights into Population History and Genomic Discovery in Africa.

Genomic studies in African populations provide unique opportunities to understand disease etiology, human diversity, and population history. In the largest study of its kind, comprising genome-wide data from 6,400 individuals and whole-genome sequences from 1,978 individuals from rural Uganda, we find evidence of geographically correlated fine-scale population substructure. Historically, the ancestry of modern Ugandans was best represented by a mixture of ancient East African pastoralists. We demonstrate the value of the largest sequence panel from Africa to date as an imputation resource. Examining 34 cardiometabolic traits, we show systematic differences in trait heritability between European and African populations, probably reflecting the differential impact of genes and environment. In a multi-trait pan-African GWAS of up to 14,126 individuals, we identify novel loci associated with anthropometric, hematological, lipid, and glycemic traits. We find that several functionally important signals are driven by Africa-specific variants, highlighting the value of studying diverse populations across the region.

Peer support for people living with hepatitis B virus-A foundation for treatment expansion.

Chronic hepatitis B infection (CHB) affects 300 million people worldwide and is being targeted by the United Nations 2030 Sustainable Development Goals (SDGs) and the World Health Organisation (WHO), working towards elimination of hepatitis B virus (HBV) as a public health threat. In this piece, we explore the evidence and potential impact of peer support to enhance and promote interventions for people living with CHB. Peer support workers (PSWs) are those with lived experience of an infection, condition or situation who work to provide support for others, aiming to improve education, prevention, treatment and other clinical interventions and to reduce the physical, psychological and social impacts of disease. Peer support has been shown to be a valuable tool for improving health outcomes for people living with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), but to date has not been widely available for communities affected by HBV. HBV disproportionately affects vulnerable and marginalised populations, who could benefit from PSWs to help them navigate complicated systems and provide advocacy, tackle stigma, improve education and representation, and optimise access to treatment and continuity of care. The scale up of peer support must provide structured and supportive career pathways for PSWs, account for social and cultural needs of different communities, adapt to differing healthcare systems and provide flexibility in approaches to care. Investment in peer support for people living with CHB could increase diagnosis, improve retention in care, and support design and roll out of interventions that can contribute to global elimination goals.

A Comparison of Self-reported Condomless Sex and Yc-DNA Biomarker Data from Young Women Engaged in High Risk Sexual Activity in Kampala, Uganda.

Reporting of condom-use can limit researchers' understanding of high-risk sexual behaviours. We compared self-reported condom-use with the Yc-DNA biomarker data and investigated potential factors influencing participation in, and reporting of, sexual behaviours. Self-reported data were collected using Audio Computer Assisted Self Interviews (ACASI) and samples for Yc-DNA biomarker were collected using self-administered and health worker-collected vaginal swabs from 644 women (aged 15-24 years) who were not living with HIV. Yc-DNA results and interview data were compared using McNemar-Bowker Analysis and Cohen's Kappa. Test statistics for Yc-DNA biomarker were calculated. Log Binomial models for Yc-DNA and self-reported results were conducted to assess for association. We found strong evidence (p < 0.001) for a difference between Yc-DNA and self-reported results. 13.7% of participants reported consistent condom-use with all partners, regardless of HIV status. Self-reported condom-use was discordant in 50.0% (n = 206) of cases, when compared to Yc-DNA results. Positive Yc-DNA results were found to be associated with older age (RR 1.36; 95%CI 1.04, 1.76 p = 0.023). Self-reported condom-use with partners with unknown HIV status was associated with higher education (RR 0.76; 95%CI 0.58,0.99 p = 0.043). Sensitivity analysis did not determine difference between methods for controlling for missing data. We found significant under-reporting of condomless sex in the self-reported data when compared to Yc-DNA results.

Cultural Adaption, Translation, Preliminary Reliability and Validity of Key Psychological and Behavioural Measures for 18 to 25 Year-Olds Living with HIV in Uganda: A Multi-Stage Approach.

HIV remains a significant public health issue among young adults living in Uganda. There is a need for reliable and valid measures of key psychological and behavioural constructs that are related to important outcomes for this population. We translated, adapted and tested the psychometric properties of questionnaires measuring HIV stigma, HIV disclosure cognitions and affect, antiretroviral therapy (ART) adherence, social support, personal values, and hope, using a multi-step process. This included: translation, back-translation, expert review, cognitive interviewing, readability and assessments of internal consistency with 93 young adults (18-25 years) living with perinatally acquired HIV in Uganda. Preliminary criterion validity was assessed by examining relationships between the adapted measures and wellbeing, HIV disclosure behaviour, HIV disclosure intention and viral load suppression. The measures all showed acceptable reliability and every questionnaire apart from the Agentic and Communal Value Scale was easy to read. Those scales measuring HIV disclosure affect and cognitions, social support, HIV stigma and hope showed relationships with other constructs suggestive of validity. There is preliminary evidence to support the use of these measures in research and clinical contexts for young adults living with perinatally acquired HIV in Uganda.

The HIV Empowering Adults' Decisions to Share: UK/Uganda (HEADS-UP) Study-A Randomised Feasibility Trial of an HIV Disclosure Intervention for Young Adults with Perinatally Acquired HIV.

Young adults with perinatally acquired HIV (PAH) face numerous challenges, including antiretroviral therapy (ART) adherence, managing onward HIV transmission risks and maintaining wellbeing. Sharing one's HIV status with others (onward HIV disclosure) may assist with these challenges but this is difficult. We developed and tested the feasibility of an intervention to help HIV status sharing decision-making for young adults with PAH. The study used a randomised parallel group feasibility design with 18-25-year-olds in Uganda and 18-29 year-olds in the UK. Participants were randomly assigned to intervention or standard of care (SOC) condition. The intervention consisted of four sessions (3 group, 1 individual) with follow-up support, delivered in person in Uganda and remotely in the UK. Assessments were carried out at: Pre-intervention /baseline; Post-intervention (intervention group only); Six-month follow-up. 142 participants were recruited (94 Uganda, 48 UK; 89 female, 53 male). At six-month follow-up, 92/94 (98%) participants were retained in Uganda, 25/48 (52%) in the UK. Multivariate analysis of combined data from both countries, showed a non-significant effect of intervention condition on HIV disclosure cognitions and affect (p = 0.08) and HIV disclosure intention (p = 0.09). There was a significant intervention effect on well-being (p = 0.005). This study addressed important gaps in understanding acceptable and feasible ways of delivering HIV status sharing support for young people living with PAH across two very different settings. The intervention was acceptable in both countries and feasible in Uganda. In the UK, retention may have been affected by its remote delivery.Trial registration: ISRCTN Registry, ISRCTN31852047, Registered on 21 January 2019.

HIV, Social Networks, and Loneliness among Older Adults in Uganda.

Loneliness among older adults has been identified as a major public health problem. Yet little is known about loneliness, or the potential role of social networks in explaining loneliness, among older people with HIV (PWH) in sub-Saharan Africa, where 70% of PWH reside. To explore this issue, we analyzed data from 599 participants enrolled in the Quality of Life and Ageing with HIV in Rural Uganda study, including older adults with HIV in ambulatory care and a comparator group of people without HIV of similar age and gender. The 3-item UCLA Loneliness Scale was used to measure loneliness, and HIV status was the primary explanatory variable. The study found no statistically significant correlation between loneliness and HIV status. However, individuals with HIV had smaller households, less physical and financial support, and were less socially integrated compared to those without HIV. In multivariable logistic regressions, loneliness was more likely among individuals who lived alone (aOR:3.38, 95% CI:1.47-7.76) and less likely among those who were married (aOR:0.34, 95% CI:0.22-0.53) and had a higher level of social integration (aOR:0.86, 95% CI: 0.79-0.92). Despite having smaller social networks and less support, older adults with HIV had similar levels of loneliness as those without HIV, which may be attributed to resiliency and access to HIV-related health services among individuals with HIV. Nonetheless, further research is necessary to better understand the mechanisms involved.

Understanding the contexts in which female sex workers sell sex in Kampala, Uganda: a qualitative study.

BACKGROUND: Structural, interpersonal and individual level factors can present barriers for HIV prevention behaviour among people at high risk of HIV acquisition, including women who sell sex. In this paper we document the contexts in which women selling sex in Kampala meet and provide services to their clients. METHODS: We collected qualitative data using semi-structured interviews. Women were eligible to participate if they were 18 years or older, self-identified as sex workers or offered sex for money and spoke Luganda or English. Ten women who met clients in venues and outdoor locations were selected randomly from a clinic for women at high risk of HIV acquisition. Ten other women who met clients online were recruited using snowball sampling. Interviews included demographic data, and themes included reasons for joining and leaving sex work, work locations, nature of relationships with clients and peers, interaction with authorities, regulations on sex work, and reported stigma. We conducted interviews over three months. Data were analysed thematically using a framework analysis approach. The coding framework was based on structural factors identified from literature, but also modified inductively with themes arising from the interviews. RESULTS: Women met clients in physical and virtual spaces. Physical spaces included venues and outdoor locations, and virtual spaces were online platforms like social media applications and websites. Of the 20 women included, 12 used online platforms to meet clients. Generally, women from the clinic sample were less educated and predominantly unmarried, while those from the snowball sample had more education, had professional jobs, or were university students. Women from both samples reported experiences of stigma, violence from clients and authorities, and challenges accessing health care services due to the illegality of sex work. Even though all participants worked in settings where sex work was illegal and consequently endured harsh treatment, those from the snowball sample faced additional threats of cybersecurity attacks, extortion from clients, and high levels of violence from clients. CONCLUSIONS: To reduce risk of HIV acquisition among women who sell sex, researchers and implementers should consider these differences in contexts, challenges, and risks to design innovative interventions and programs that reach and include all women.

Violence outcomes in later adolescence with the Good School Toolkit-Primary: a nonrandomized controlled trial in Uganda.

BACKGROUND: We sought to determine whether the Good School Toolkit-Primary violence prevention intervention was associated with reduced victimisation and perpetration of peer and intimate partner violence four years later, and if any associations were moderated by sex and early adolescent: family connectedness, socio-economic status, and experience of violence outside of school. METHODS: Drawing on schools involved in a randomised controlled trial of the intervention, we used a quasi-experimental design to compare violence outcomes between those who received the intervention during our trial (n = 1388), and those who did not receive the intervention during or after the trial (n = 522). Data were collected in 2014 (mean age 13.4, SD 1.5 years) from participants in 42 schools in Luwero District, Uganda, and 2018/19 from the same participants both in and out of school (mean age 18, SD: 1.77 years). We compared children who received the Good School Toolkit-Primary, a whole school violence prevention intervention, during a randomised controlled trial, to those who did not receive the intervention during or after the trial. Outcomes were measured using items adapted from the International Society for the Prevention of Child Abuse and Neglect Child Abuse Screening Tool-Child Institutional. We used mixed-effect multivariable logistic regression, with school fitted as a random-effect to account for clustering. RESULTS: 1910 adolescents aged about 16-19 years old were included in our analysis. We found no evidence of an average long-term intervention effect on our primary outcome, peer violence victimization at follow-up (aOR = 0.81, 95%CI = 0.59-1.11); or for any secondary outcome. However, exposure to the intervention was associated with: later reductions in peer violence, for adolescents with high family connectedness (aOR = 0.70, 95% CI 0.49 to 0.99), but not for those with low family connectedness (aOR = 1.07, 95% CI 0.69 to 1.6; p-interaction = 0.06); and reduced later intimate partner violence perpetration among males with high socio-economic status (aOR = 0.32, 95%CI 0.11 to 0.90), but not low socio-economic status (aOR = 1.01 95%CI 0.37 to 2.76, p-interaction = 0.05). CONCLUSIONS: Young adolescents in connected families and with higher socio-economic status may be better equipped to transfer violence prevention skills from primary school to new relationships as they get older. TRIAL REGISTRATION: Clinicaltrials.gov, NCT01678846, registration date 24 August 2012. Protocol for this paper:  https://www.researchprotocols.org/2020/12/e20940 .

Exploring the consent process among pregnant and breastfeeding women taking part in a maternal vaccine clinical trial in Kampala, Uganda: a qualitative study.

BACKGROUND: The involvement of pregnant women in vaccine clinical trials presents unique challenges for the informed consent process. We explored the expectations and experiences of the pregnant women, spouses/partners, health workers and stakeholders of the consent process during a Group B Streptococcus maternal vaccine trial. METHODS: We interviewed 56 participants including pregnant women taking part in the trial, women not in the trial, health workers handling the trial procedures, spouses, and community stakeholders. We conducted 13 in-depth interviews and focus group discussions with 23 women in the trial, in-depth interviews with 5 spouses, and 5 women not in the trial, key informant interviews with 5 health workers and 5 other stakeholders were undertaken. RESULTS: Decision-making by a pregnant woman to join a trial was done in consultation with spouse, parents, siblings, or trusted health workers. Written study information was appreciated by all but they suggested the use of audio and visual presentation to enhance understanding. Women stressed the need to ensure that their male partners received study information before their pregnant partners joined a clinical trial. Confidentiality in research was emphasised differently by individual participants; while some emphasised it for self, others were keen to protect their family members from being exposed, for allowing them to be involved in research. However, others wanted their community participation to be acknowledged. CONCLUSION: We found that pregnant women make decisions to join a clinical trial after consulting with close family. Our findings suggest the need for an information strategy which informs not only the pregnant woman, but also her family about the research she is invited to engage in.

A scoping review of ethics review processes during public health emergencies in Africa.

BACKGROUND: The COVID-19 pandemic forced governments, multilateral public health organisations and research institutions to undertake research quickly to inform their responses to the pandemic. Most COVID-19-related studies required swift approval, creating ethical and practical challenges for regulatory authorities and researchers. In this paper, we examine the landscape of ethics review processes in Africa during public health emergencies (PHEs). METHODS: We searched four electronic databases (Web of Science, PUBMED, MEDLINE Complete, and CINAHL) to identify articles describing ethics review processes during public health emergencies and/or pandemics. We selected and reviewed those articles that were focused on Africa. We charted the data from the retrieved articles including the authors and year of publication, title, country and disease(s) reference, broad areas of (ethical) consideration, paper type, and approach. RESULTS: Of an initial 4536 records retrieved, we screened the titles and abstracts of 1491 articles, and identified 72 articles for full review. Nine articles were selected for inclusion. Of these nine articles, five referenced West African countries including Liberia, Guinea and Sierra Leone, and experiences linked to the Ebola virus disease. Two articles focused on South Africa and Kenya, while the other two articles discussed more general experiences and pitfalls of ethics review during PHEs in Africa more broadly. We found no articles published on ethics review processes in Africa before the 2014 Ebola outbreak, and only a few before the COVID-19 outbreak. Although guidelines on protocol review and approval processes for PHEs were more frequently discussed after the 2014 Ebola outbreak, these did not focus on Africa specifically. CONCLUSIONS: There is a gap in the literature about ethics review processes and preparedness within Africa during PHEs. This paper underscores the importance of these processes to inform practices that facilitate timely, context-relevant research that adequately recognises and reinforces human dignity within the quest to advance scientific knowledge about diseases. This is important to improve fast responses to PHEs, reduce mortality and morbidity, and enhance the quality of care before, during, and after pandemics.

Discovery and fine-mapping of kidney function loci in first genome-wide association study in Africans.

Genome-wide association studies (GWAS) of kidney function have uncovered hundreds of loci, primarily in populations of European ancestry. We have undertaken the first continental African GWAS of estimated glomerular filtration rate (eGFR), a measure of kidney function used to define chronic kidney disease (CKD). We conducted GWAS of eGFR in 3288 East Africans from the Uganda General Population Cohort (GPC) and replicated in 8224 African Americans from the Women's Health Initiative. Loci attaining genome-wide significant evidence for association (P < 5 × 10-8) were followed up with Bayesian fine-mapping to localize potential causal variants. The predictive power of a genetic risk score (GRS) constructed from previously reported trans-ancestry eGFR lead single nucleotide polymorphism (SNPs) was evaluated in the Uganda GPC. We identified and validated two eGFR loci. At the glycine amidinotransferase (GATM) locus, the association signal (lead SNP rs2433603, P = 1.0 × 10-8) in the Uganda GPC GWAS was distinct from previously reported signals at this locus. At the haemoglobin beta (HBB) locus, the association signal (lead SNP rs141845179, P = 3.0 × 10-8) has been previously reported. The lead SNP at the HBB locus accounted for 88% of the posterior probability of causality after fine-mapping, but did not colocalise with kidney expression quantitative trait loci. The trans-ancestry GRS of eGFR was not significantly predictive into the Ugandan population. In the first GWAS of eGFR in continental Africa, we validated two previously reported loci at GATM and HBB. At the GATM locus, the association signal was distinct from that previously reported. These results demonstrate the value of performing GWAS in continental Africans, providing a rich genomic resource to larger consortia for further discovery and fine-mapping. The study emphasizes that additional large-scale efforts in Africa are warranted to gain further insight into the genetic architecture of CKD.

Prevalence of Curable Sexually Transmitted Infections in a Population-Representative Sample of Young Adults in a High HIV Incidence Area in South Africa.

BACKGROUND: Recent population-representative estimates of sexually transmitted infection (STI) prevalence in high HIV burden areas in southern Africa are limited. We estimated the prevalence and associated factors of 3 STIs among adolescents and young adults (AYA) in rural South Africa. METHODS: Between March 2020 and May 2021, a population-representative sample of AYA aged 16 to 29 years were randomly selected from a Health and Demographic Surveillance Site in rural KwaZulu-Natal, South Africa, for a 2 × 2 factorial randomized controlled trial. Participants in 2 intervention arms were offered baseline testing for gonorrhea, chlamydia, and trichomoniasis using GeneXpert. Prevalence estimates were weighted for participation bias, and logistic regression models were used to assess factors associated with STIs. RESULTS: Of 2323 eligible AYA, 1743 (75%) enrolled in the trial. Among 863 eligible for STI testing, 814 (94%) provided specimens (median age of 21.8 years, 52% female, and 71% residing in rural areas). Population-weighted prevalence estimates were 5.0% (95% confidence interval [CI], 4.2%-5.8%) for gonorrhea, 17.9% (16.5%-19.3%) for chlamydia, 5.4% (4.6%-6.3%) for trichomoniasis, and 23.7% (22.2%-25.3%) for any STI. In multivariable models, female sex (adjusted odds ratio [aOR], 2.24; 95% CI, 1.48-3.09) and urban/periurban (vs. rural) residence (aOR, 1.48; 95% CI, 1.02-2.15) were associated with STIs; recent migration was associated with lower odds of STI (aOR, 0.37; 95% CI, 0.15-0.89). Among those with an STI, 53 (31.0%) were treated within 7 days; median time to treatment was 11 days (interquartile range, 6-77 days). CONCLUSIONS: We identified a high prevalence of curable STIs among AYA in rural South Africa. Improved access to STI testing to enable etiologic diagnosis and rapid treatment is needed.

Factors Associated with Short and Long Term Mobility and HIV Risk of Women Living in Fishing Communities Around Lake Victoria in Kenya, Tanzania, and Uganda: A Cross Sectional Survey.

Mobility is linked to negative HIV care continuum outcomes. We sought to understand factors associated with short and long term mobility among women in fishing communities in Kenya, Tanzania, and Uganda. From 2018 through 2019 we conducted a cross-sectional survey of women aged 15 years and above, randomly selected from a census of six fishing villages, around Lake Victoria. Data collected included: demographics, risky sexual behaviour on the most recent trip, and travel behaviour in the previous 4 months. Mobility was recorded as any overnight trip outside the participant's village. A two-level multinomial logistic regression model was used to determine the associated factors. A total of 901 participants were enrolled, of whom 645 (71.6%) reported travelling (53.4%; short and 18.2% long term trips). Five factors were associated with long term travel: age, travel purpose, frequency of travel, sexual behaviour while travelling, and destination. Trips made by women aged 46-75 years were less likely to be long term. Long term trips were more common if the trip was to visit, rather than to trade, and more common for women who reported one or two trips rather than three or more trips. Women who made long term trips were more likely to engage in unprotected sex while on a trip. Women who travelled to a regional town/district or another town/district were more likely to take long term trips. The factors associated with travel duration among women living in fishing communities could inform planning of future health care interventions in these communities.

Is hope associated with HIV-acquisition risk and intimate partner violence amongst young women and men? A cross-sectional study in urban informal settlements in South Africa.

Hope is a concept that may mediate between the structural constraints people live under and their HIV-acquisition risk behaviours/experiences. Drawing on data collected as the baseline for an intervention trial between September 2015 and September 2016, among young (18-30-year-old), out-of-school women and men in urban informal settlements in Durban, South Africa, we assess whether hope, assessed by the Snyder Hope Scale, is associated with HIV-risk behaviours/experiences. 677 women (35.5%; 33.7%; 30.9%; low, medium, and high hope scores respectively) and 668 men (40.6%; 32.8%; 26.7%; low, medium, and high hope scores respectively) were included. Among women, adjusted analyses showed high levels of hope, compared to low levels, were associated with greater modern contraceptive use (aOR1.57, 1.04-2.37). For men, medium or high levels of hope, compared to low levels, were associated with reduced physical and/or sexual IPV perpetration (med: aOR0.55, 0.38-0.81, high: 0.38, 0.25-0.57), emotional IPV perpetration (med: aOR0.54, 0.36-0.80, high: aOR0.62, 0.41-0.94) and transactional sex (med: 0.57, 0.38-0.84, high: aOR0.57, 0.39-0.86) respectively. For men, hope potentially captured a pathway between an individual's structural context and their HIV-risk behaviour. Yet this was not the case for women. It may be the Snyder Hope Scale does not adequately capture localised meanings of hope.

Exploring the extent of mental health practice: content and cluster analysis of techniques used in HIV testing and counselling sessions in Uganda.

There is an urgent need for greater provision of mental health services to people living with HIV. HIV testing and counselling (HTC) sessions diagnose HIV and offer appropriate psychosocial support and behavioural messages to support people to link into HIV care. It is not known to what extent HTC currently addresses mental health. We examined transcriptions of 116 audio-recorded HTC sessions delivered in Uganda against a checklist of mental health techniques. Hierarchical cluster analysis explored co-occurrence of techniques. Core counselling skills were very commonly present, and co-occurred. Assessment techniques were not commonly seen. Specific therapy techniques to treat anxiety or depression were not present. HTC staff are a resource for delivering mental health care for people with HIV, owing to their strong fundamental counselling skills. However, training is needed in assessment and evidence-based therapies. Provision of fuller assessment and interventions may increase detection and signposting for mental health and alcohol use, both of which may affect linkage into care. HTC staff have fundamental skills that could also be developed to train and supervise other staff to provide much needed mental health support to people living with HIV. Future research should develop brief mental health interventions for delivery by HTC staff.

Modelling the impact of combining HIV prevention interventions on HIV dynamics in fishing communities in Uganda.

BACKGROUND: In countries with mature generalized HIV epidemics such as Uganda, there are still groups of individuals that are disproportionately affected. Among the key populations in Uganda are fishing communities, which make up about 10% of the population. Compared to the general population, HIV prevalence and incidence among individuals living in these communities is high. This high HIV burden has been attributed to several factors including limited access to prevention and treatment services as well as ongoing high-risk sexual behaviour. METHODS: We investigated the impact of combined HIV prevention interventions on HIV transmission dynamics in high-risk fishing communities in Uganda using a deterministic compartmental model. The model was calibrated to seroprevalence data from a census performed in 2014. To account for remaining uncertainty in the calibrated model parameters, 50 000 simulated scenarios were modelled to investigate the impact of combined prevention interventions. RESULTS: The projected HIV incidence decreased from 1.87 per 100 PY without intervention scale-up to 0.25 per 100 PY after 15 years (2014-2029) of intervention scale-up. A potential combination achieving this 87% reduction in incidence over 15 years in Ugandan FCs included condom use in about 60% of sexual acts, 23% of susceptible men circumcised, 87% of people living with HIV aware of their status, 75% of those on ART, and about 3% of susceptible individuals on oral PrEP. Uncertainty analysis revealed relative reductions in incidence ranging from 30.9 to 86.8%. Sensitivity analyses suggested that condom use and early ART were the most important interventions. CONCLUSION: Reducing HIV incidence, as well as prevalence and AIDS-related mortality, in these high-risk fishing communities in Uganda is attainable over 15 years with a combination prevention package. Our projected intervention coverage levels are well within the national targets set by the Uganda government and enable coming close to reaching the UNAIDS 95-95-95 targets to end AIDS as a public health threat by 2030.

Managing household income and antiretroviral therapy adherence among people living with HIV in a low-income setting: a qualitative data from the HPTN 071 (PopART) trial in South Africa.

BACKGROUND: South Africa is reported to have the highest burden of HIV with an estimated 8.2 million people living with HIV (PLHIV) in 2021- despite adopting the World Health Organisation (WHO) universal HIV test and treat (UTT) recommendations in 2016. As of 2021, only an estimated 67% (5.5 million) of all PLHIV were accessing antiretroviral therapy (ART), as per recorded clinic appointments attendance. Studies in sub-Saharan Africa show that people living in low-income households experience multiple livelihood-related barriers to either accessing or adhering to HIV treatment including lack of resources to attend to facilities and food insecurity. We describe the interactions between managing household income and ART adherence for PLHIV in low-income urban and semi-urban settings in the Western Cape, South Africa. METHODS: We draw on qualitative data collected as part of the HPTN 071 (PopART) HIV prevention trial (2016 - 2018) to provide a detailed description of the interactions between household income and self-reported ART adherence (including accessing ART and the ability to consistently take ART as prescribed) for PLHIV in the Western Cape, South Africa. We included data from 21 PLHIV (10 men and 11 women aged between 18 and 70 years old) from 13 households. As part of the qualitative component, we submitted an amendment to the ethics to recruit and interview community members across age ranges. We purposefully sampled for diversity in terms of age, gender, and household composition. RESULTS: We found that the management of household income interacted with people's experiences of accessing and adhering to ART in diverse ways. Participants reported that ART adherence was not a linear process as it was influenced by income stability, changing household composition, and other financial considerations. Participants reported that they did not have a fixed way of managing income and that subsequently caused inconsistency in their ART adherence. Participants reported that they experienced disruptions in ART access and adherence due to competing household priorities. These included difficulties balancing between accessing care and/or going to work, as well as struggling to cover HIV care-related costs above other basic needs. CONCLUSION: Our analysis explored links between managing household income and ART adherence practices. We showed that these are complex and change over the course of treatment duration. We argued that mitigating negative impacts of income fluctuation and managing complex trade-offs in households be included in ART adherence support programmes.

Thetha Nami ngithethe nawe (Let's Talk): a stepped-wedge cluster randomised trial of social mobilisation by peer navigators into community-based sexual health and HIV care, including pre-exposure prophylaxis (PrEP), to reduce sexually transmissible HIV amongst young people in rural KwaZulu-Natal, South Africa.

BACKGROUND: Antiretroviral therapy (ART) through universal test and treat (UTT) and HIV pre-exposure prophylaxis (PrEP) substantially reduces HIV-related mortality and incidence. Effective ART based prevention has not translated into population-level impact in southern Africa due to sub-optimal coverage among youth. We aim to investigate the effectiveness, implementation and cost effectiveness of peer-led social mobilisation into decentralised integrated HIV and sexual reproductive health (SRH) services amongst adolescents and young adults in KwaZulu-Natal (KZN). METHODS: We are conducting a type 1a hybrid effectiveness/implementation study, with a cluster randomized stepped-wedge trial (SWT) to assess effectiveness and a realist process evaluation to assess implementation outcomes. The SWT will be conducted in 40 clusters in rural KZN over 45 months. Clusters will be randomly allocated to receive the intervention in period 1 (early) or period 2 (delayed). 1) Intervention arm: Resident peer navigators in each cluster will approach young men and women aged 15-30 years living in their cluster to conduct health, social and educational needs assessment and tailor psychosocial support and health promotion, peer mentorship, and facilitate referrals into nurse led mobile clinics that visit each cluster regularly to deliver integrated SRH and differentiated HIV prevention (HIV testing, UTT for those positive, and PrEP for those eligible and negative). Standard of Care is UTT and PrEP delivered to 15-30 year olds from control clusters through primary health clinics. There are 3 co-primary outcomes measured amongst cross sectional surveys of 15-30 year olds: 1) effectiveness of the intervention in reducing the prevalence of sexually transmissible HIV; 2) uptake of universal risk informed HIV prevention intervention; 3) cost of transmissible HIV infection averted. We will use a realist process evaluation to interrogate the extent to which the intervention components support demand, uptake, and retention in risk-differentiated biomedical HIV prevention. DISCUSSION: The findings of this trial will be used by policy makers to optimize delivery of universal differentiated HIV prevention, including HIV pre-exposure prophylaxis through peer-led mobilisation into community-based integrated adolescent and youth friendly HIV and sexual and reproductive health care. TRIAL REGISTRATION: ClinicalTrials.gov Identifier-NCT05405582. Registered: 6th June 2022.

Social Categorisation and Social Identification: The Mediating Role of Social Isolation and Loneliness in Adolescents Living with HIV.

BACKGROUND: Social isolation and loneliness are associated with living with a chronic condition particularly where stigma is a factor. Our study aimed to examine the lived experience of adolescents living with HIV in relation to isolation because of their diagnosis and consequences of disclosure. Giddens' structuration theory was used as an analytic framework to identify the potential mechanisms underlying adolescents living with HIV's experiences. METHOD: Longitudinal in-depth interviews were conducted with 20 adolescents living with HIV aged 15-24 years with each participant taking part in three interviews (total 60) between September 2020 and October 2021. Thematic analysis was performed using Braun and Clarke's steps for coding and analysing qualitative data and informed by the structuration theory framework. RESULTS: The findings indicated that adolescents living with HIV have agency and make conscious choices about sharing their status. However, these choices are influenced by their experiences in their community. The discrimination and negative judgements they often experience prevent them from disclosing their status. Stigma, discrimination, and psychological distress contribute to the isolation that adolescents and young adults living with HIV experience. The limited disclosure itself can lead to them becoming isolated and lonely. CONCLUSION: The negative experiences which adolescents living with HIV face can have an impact not only on their psychological wellbeing but also on their decision to disclose and seek support. These experiences may lead to social isolation and loneliness, an unintended consequence of their action in protecting themselves from the conditions created by the structures/environment in which they live.

Respecting relational agency in the context of vulnerability: What can research ethics learn from the social sciences?

Despite advances in theory, often driven by feminist ethicists, research ethics struggles in practice to adequately account for and respond to the agency and autonomy of people considered vulnerable in the research context. We argue that shifts within feminist research ethics scholarship to better characterise and respond to autonomy and agency can be bolstered by further grounding in discourses from the social sciences, in work that confirms the complex nature of human agency in contexts of structural and other sources of vulnerability. We discuss some of the core concepts and critiques emerging from the literature on women and children's agency in under-resourced settings, highlighting calls to move from individualistic to relational models of agency, and to recognise the ambiguous, value-laden, and heterogeneous nature of the concept. We then draw out what these conceptual shifts might mean for research ethics obligations and guidance, illustrating our analysis using a case vignette based on research ethics work conducted in South Africa. We conclude that if research practices are to be supportive of agency, it will be crucial to scrutinise the moral judgements which underpin accounts of agency, derive more situated definitions of and responses to agency, and enable people and participants to influence these based on their own experiences and self-perceptions.