A mixed methods process evaluation: understanding the implementation and delivery of HIV prevention services integrated within sexual reproductive health (SRH) with or without peer support amongst adolescents and young adults in rural KwaZulu-Natal, South Africa.

BACKGROUND: Combination prevention interventions, when integrated with community-based support, have been shown to be particularly beneficial to adolescent and young peoples' sexual and reproductive health. Between 2020 and 2022, the Africa Health Research Institute in rural South Africa conducted a 2 × 2 randomised factorial trial among young people aged 16-29 years old (Isisekelo Sempilo) to evaluate whether integrated HIV and sexual and reproductive health (HIV/SRH) with or without peer support will optimise delivery of HIV prevention and care. Using mixed methods, we conducted a process evaluation to provide insights to and describe the implementation of a community-based peer-led HIV care and prevention intervention targeting adolescents and young people. METHODS: The process evaluation was conducted in accordance with the Medical Research Council guidelines using quantitative and qualitative approaches. Self-completed surveys and clinic and programmatic data were used to quantify the uptake of each component of the intervention and to understand intervention fidelity and reach. In-depth individual interviews were used to understand intervention experiences. Baseline sociodemographic factors were summarised for each trial arm, and proportions of participants who accepted and actively engaged in various components of the intervention as well as those who successfully linked to care were calculated. Qualitative data were thematically analysed. RESULTS: The intervention was feasible and acceptable to young people and intervention implementing teams. In particular, the STI testing and SRH components of the intervention were popular. The main challenges with the peer support implementation were due to fidelity, mainly because of the COVID-19 pandemic. The study found that it was important to incorporate familial support into interventions for young people's sexual health. Moreover, it was found that psychological and social support was an essential component to combination HIV prevention packages for young people. CONCLUSION: The results demonstrated that peer-led community-based care that integrates SRH services with HIV is a versatile model to decentralise health and social care. The family could be a platform to target restrictive gender and sexual norms, by challenging not only attitudes and behaviours related to gender among young people but also the gendered structures that surround them.

Effectiveness of integrating HIV prevention within sexual reproductive health services with or without peer support among adolescents and young adults in rural KwaZulu-Natal, South Africa (Isisekelo Sempilo): 2 × 2 factorial, open-label, randomised controlled trial.

BACKGROUND: Approximately 200 000 South Africans acquired HIV in 2021 despite the availability of universal HIV test and treat and pre-exposure prophylaxis (PrEP). The aim of this study was to test the effectiveness of sexual and reproductive health services or peer support, or both, on the uptake of serostatus neutral HIV services or reduction of sexually transmissible HIV. METHODS: We did an open-label, 2 × 2 randomised factorial trial among young people in a mostly rural area of KwaZulu-Natal, South Africa. Inclusion criteria included being aged 16-29 years, living in the mapped geographical areas that were accessible to the area-based peer navigators, being willing and able to provide informed consent, and being willing to provide a dried blood spot for anonymous HIV testing and HIV viral load measurement at 12 months. Participants were randomly allocated by computer-generated algorithm to one of four groups: those in the standard-of-care group were referred to youth-friendly services for differentiated HIV prevention (condoms, universal HIV test and treat with antiretroviral therapy, and PrEP if eligible); those in the sexual and reproductive health services group received baseline self-collected specimens for sexually transmitted infection (STI) testing and referral to integrated sexual and reproductive health and HIV prevention services; those in the peer support group were referred to peer navigators for health promotion, condom provision, and facilitation of attendance for differentiated HIV prevention services; and those in the final group received a combination of sexual and reproductive health services and peer support. Coprimary outcomes were linkage to clinical services within 60 days of enrolment, proportion of participants who had sexually transmissible HIV at 12 months after enrolment, and proportion of sampled individuals who consented to participation and gave a dried blood spot for HIV testing at 12 months. Logistic regression was used for analyses, and adjusted for age, sex, and rural or peri-urban area of residence. This study is registered with ClinicalTrials.gov (NCT04532307) and is closed. FINDINGS: Between March 2, 2020, and July 7, 2022, 1743 (75·7%) of 2301 eligible individuals were enrolled and followed up. 12-month dried blood spots were collected from 1168 participants (67·0%). The median age of the participants was 21 years (IQR 18-25), 51·4% were female, and 51·1% had secondary level education. Baseline characteristics and 12-month outcome ascertainment were similar between groups. 755 (43·3%) linked to services by 60 days. 430 (49·8%) of 863 who were in the sexual reproductive health services group were linked to care compared with 325 (36·9%) of 880 who were not in the sexual and reproductive health services group (adjusted odds ratio [aOR] 1·68; 95% CI 1·39-2·04); peer support had no effect: 385 (43·5%) of 858 compared with 370 (43·1%) of 885 (1·02, 0·84-1·23). At 12 months, 227 (19%) tested ELISA-positive for HIV, of whom 41 (18%) had viral loads of 400 copies per mL; overall prevalence of transmissible HIV was 3·5%. 22 (3·7%) of 578 participants in the sexual and reproductive health services group had transmissible HIV compared with 19 (3·3%) of 590 not in the sexual and reproductive health services group (aOR 1·12; 95% CI 0·60-2·11). The findings were also non-significant for peer support: 21 (3·3%) of 565 compared with 20 (3·3%) of 603 (aOR 1·03; 95% CI 0·55-1·94). There were no serious adverse events or deaths during the study. INTERPRETATION: This study provides evidence that STI testing and sexual and reproductive health services create demand for serostatus neutral HIV prevention in adolescents and young adults in Africa. STI testing and integration of HIV and sexual health has the potential to reach those at risk and tackle unmet sexual health needs. FUNDING: US National Institute of Health, Bill & Melinda Gates Foundation, and 3ie.

Uptake of multi-level HIV interventions and HIV-related behaviours among young people in rural South Africa.

Combination HIV prevention packages have reduced HIV incidence and improved HIV-related outcomes among young people. However, there is limited data on how package components interact to promote HIV-related prevention behaviours. We described the uptake of HIV prevention interventions supported by Determined, Resilient, Empowered, AIDS-free, Motivated and Safe (DREAMS) Partnership and assessed the association between uptake and HIV-related behaviours among young people in rural KwaZulu-Natal, South Africa. We analysed two cohorts followed from May 2017 to December 2019 to evaluate the impact of DREAMS, covering 13-29 year-old females, and 13-35 year-old males. DREAMS interventions were categorised as healthcare-based or social. We described the uptake of interventions and ran logistic regression models to investigate the association between intervention uptake and subsequent protective HIV-related outcomes including no condomless sex and voluntary medical male circumcision (VMMC). For each outcome, we adjusted for socio-demographics and sexual/pregnancy history and reported adjusted odds ratios (aOR) and 95% confidence intervals (CI). Among 5248 participants, uptake of healthcare interventions increased from 2018 to 2019 by 8.1% and 3.7% for males and females respectively; about half of participants reported receiving both healthcare and social interventions each year. The most utilised combinations of interventions included HIV testing and counselling, school-based HIV education and cash transfers. Participation in social interventions only compared to no intervention was associated with reduced condomless sex (aOR = 1.60, 95%CI: 1.03-2.47), while participation in healthcare interventions only was associated with increased condomless sex. The uptake of interventions did not significantly affect subsequent VMMC overall. Among adolescent boys, exposure to school-based HIV education, cash transfers and HIV testing and counselling was associated with increase in VMMC (aOR = 1.79, 95%CI: 1.04-3.07). Multi-level HIV prevention interventions were associated with an increase in protective HIV-related behaviours emphasizing the importance of accessible programs within both school and community settings for young people.

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.

The met and unmet health needs for HIV, hypertension, and diabetes in rural KwaZulu-Natal, South Africa: analysis of a cross-sectional multimorbidity survey.

BACKGROUND: The convergence of infectious diseases and non-communicable diseases in South Africa is challenging to health systems. In this analysis, we assessed the multimorbidity health needs of individuals and communities in rural KwaZulu-Natal and established a framework to quantify met and unmet health needs for individuals living with infectious and non-communicable diseases. METHODS: We analysed data collected between May 25, 2018, and March 13, 2020, from participants of a large, community-based, cross-sectional multimorbidity survey (Vukuzazi) that offered community-based HIV, hypertension, and diabetes screening to all residents aged 15 years or older in a surveillance area in the uMkhanyakude district in KwaZulu-Natal, South Africa. Data from the Vukuzazi survey were linked with data from demographic and health surveillance surveys with a unique identifier common to both studies. Questionnaires were used to assess the diagnosed health conditions, treatment history, general health, and sociodemographic characteristics of an individual. For each condition (ie, HIV, hypertension, and diabetes), individuals were defined as having no health needs (absence of condition), met health needs (condition that is well controlled), or one or more unmet health needs (including diagnosis, engagement in care, or treatment optimisation). We analysed met and unmet health needs for individual and combined conditions and investigated their geospatial distribution. FINDINGS: Of 18 041 participants who completed the survey (12 229 [67·8%] were female and 5812 [32·2%] were male), 9898 (54·9%) had at least one of the three chronic diseases measured. 4942 (49·9%) of these 9898 individuals had at least one unmet health need (1802 [18·2%] of 9898 needed treatment optimisation, 1282 [13·0%] needed engagement in care, and 1858 [18·8%] needed a diagnosis). Unmet health needs varied by disease; 1617 (93·1%) of 1737 people who screened positive for diabetes, 2681 (58·2%) of 4603 people who screened positive for hypertension, and 1321 (21·7%) of 6096 people who screened positive for HIV had unmet health needs. Geospatially, met health needs for HIV were widely distributed and unmet health needs for all three conditions had specific sites of concentration; all three conditions had an overlapping geographical pattern for the need for diagnosis. INTERPRETATION: Although people living with HIV predominantly have a well controlled condition, there is a high burden of unmet health needs for people living with hypertension and diabetes. In South Africa, adapting current, widely available HIV care services to integrate non-communicable disease care is of high priority. FUNDING: Fogarty International Center and the National Institutes of Health, the Bill & Melinda Gates Foundation, the South African Department of Science and Innovation, the South African Medical Research Council, the South African Population Research Infrastructure Network, and the Wellcome Trust. TRANSLATION: For the isiZulu translation of the abstract see Supplementary Materials section.

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.

Evaluating use of mass-media communication intervention 'MTV-Shuga' on increased awareness and demand for HIV and sexual health services by adolescent girls and young women in South Africa: an observational study.

OBJECTIVE: To investigate the effect of exposure to MTV Shuga:Down South' (MTVShuga-DS) during the scale-up of combination HIV-prevention interventions on awareness and uptake of sexual reproductive health (SRH) and HIV-prevention services by adolescent girls and young women (AGYW). DESIGN: One longitudinal and three cross-sectional surveys of representative samples of AGYW. SETTING: AGYW in four South African districts with high HIV prevalence (>10%) (May 2017 and September 2019). PARTICIPANTS: 6311 AGYW aged 12-24. MEASURES: Using logistic regression, we measured the relationship between exposure to MTV Shuga-DS and awareness of pre-exposure prophylaxis (PrEP), condom use at last sex, uptake of HIV-testing or contraception, and incident pregnancy or herpes simplex virus 2 (HSV-2) infection. RESULTS: Within the rural cohort 2184 (85.5%) of eligible sampled individuals were enrolled, of whom 92.6% had at least one follow-up visit; the urban cross-sectional surveys enrolled 4127 (22.6%) of eligible sampled individuals. Self-report of watching at least one MTV Shuga-DS episode was 14.1% (cohort) and 35.8% (cross-section), while storyline recall was 5.5% (cohort) and 6.7% (cross-section). In the cohort, after adjustment (for HIV-prevention intervention-exposure, age, education, socioeconomic status), MTVShuga-DS exposure was associated with increased PrEP awareness (adjusted OR (aOR) 2.06, 95% CI 1.57 to 2.70), contraception uptake (aOR 2.08, 95% CI 1.45 to 2.98) and consistent condom use (aOR 1.84, 95% CI 1.24 to 2.93), but not with HIV testing (aOR 1.02, 95% CI 0.77 to 1.21) or acquiring HSV-2 (aOR 0.92, 95% CI 0.61 to 1.38). In the cross-sections, MTVShuga-DS was associated with greater PrEP awareness (aOR 1.7, 95% CI 1.20 to 2.43), but no other outcome. CONCLUSIONS: Among both urban and rural AGYW in South Africa, MTVShuga-DS exposure was associated with increased PrEP awareness and improved demand for some HIV prevention and SRH technologies but not sexual health outcomes. However, exposure to MTVShuga-DS was low. Given these positive indications, supportive programming may be required to raise exposure and allow future evaluation of edu-drama impact in this setting.

Adaptation and pre-test of a shortened Stepping Stones and Creating Futures intervention focused on HIV for young men in rural South Africa.

Men's engagement in HIV prevention and treatment is suboptimal, including in South Africa. We sought to address this through adapting an evidence-based intervention, Stepping Stones and Creating Futures (SSCF), to strengthen its HIV content and provide a more scalable (shorter) intervention in rural South Africa. We then conducted a mixed methods pre-test of the intervention among young men aged 18-35 years. To adapt SSCF, we reviewed the current evidence base and worked with male Peer Navigators to update the SSCF theory of change (ToC) and manual. The revised intervention was ~45 hours (9 sessions) as opposed to ~63 hours and included a greater focus on HIV prevention and treatment technologies. Overall, 64% (n = 60) of men approached agreed to participate in the intervention, uptake (attending one session) among those who agreed was n = 35(58%) and retention (attending 6 or more sessions) was n = 25(71%). Qualitative data emphasized the intervention was acceptable, with young men describing it as something they liked. The qualitative data also broadly supported the intervention ToC, including the normalization of HIV in men's lives, and the importance of health for men in achieving their life goals. However, it also highlighted the need to focus more on HIV-related stigma and fear, and the importance of HIV self-testing kits in encouraging testing. We revised the ToC and manual in light of this data. The adapted SSCF is acceptable and supports the ToC. Next steps is an evaluation to look at effectiveness of the intervention.

The association of exposure to DREAMS on sexually acquiring or transmitting HIV amongst adolescent girls and young women living in rural South Africa.

OBJECTIVE: We investigate how risk of sexually acquiring or transmitting HIV in adolescent girls and young women (AGYW) changed following the real-world implementation of DREAMS (Determined, Resilient, Empowered, AIDS free, Mentored and Safe) HIV prevention programme. DESIGN: A representative population-based prospective cohort study of AGYW living in rural KwaZulu-Natal. METHODS: Between 2017 and 2019, we interviewed a random sample of AGYW aged 13-22 years annually. We measured exposure to DREAMS as self-reported receipt of an invitation to participate and/or participation in DREAMS activities that were provided by DREAMS implementing organizations. HIV and herpes simplex virus type 2 (HSV-2) statuses were ascertained through blood tests on Dried Blood Spot (DBS). We used multivariable regression analysis to assess the association between exposure to DREAMS and risk of acquiring HIV: measured as incident HSV-2 (a proxy of sexual risk) and incident HIV;and the risk of sexually transmitting HIV: measured as being HIV positive with a detectable HIV viral load (≥50 copie/ml) on the last available DBS. We adjusted for sociodemographic, sexual relationship, and migration. RESULTS: Two thousand one hundred and eighty-four (86.4%) of those eligible agreed to participate and 2016 (92.3%) provided data for at least one follow-up time-point. One thousand and thirty (54%) were exposed to DREAMS;HIV and HSV-2 incidence were 2.2/100 person-years [95% confidence interval (CI) 1.66-2.86] and 17.3/100 person-years (95% CI 15.5-19.4), respectively. There was no evidence that HSV-2 and HIV incidence were lower in those exposed to DREAMS: adjusted rate ratio (aRR) 0.96 (95% CI 0.76-1.23 and 0.83 (95% CI 0.46-1.52), respectively. HIV viral load was detectable for 169 (8.9%) respondents;there was no evidence this was lower in those exposed to DREAMS with an adjusted risk difference, compared with those not exposed to DREAMS, of 0.99% (95% CI-1.52 to 3.82]. Participants who lived in peri-urban/ urban setting were more likely to have incident HIV and transmissible HIV. Both HSV-2 incidence and the transmissible HIV were associated with older age and ever having sex. Findings did not differ substantively by respondent age group. CONCLUSION: DREAMS exposure was not associated with measurable reductions in risk of sexually acquiring or transmitting HIV amongst a representative cohort of AGYW in rural South Africa.

Isisekelo Sempilo study protocol for the effectiveness of HIV prevention embedded in sexual health with or without peer navigator support (Thetha Nami) to reduce prevalence of transmissible HIV amongst adolescents and young adults in rural KwaZulu-Natal: a 2 × 2 factorial randomised controlled trial.

BACKGROUND: Antiretroviral therapy (ART) through universal test and treat (UTT) and HIV pre-exposure prophylaxis (PrEP) substantially reduces HIV-related mortality, morbidity and incidence. Effective individual-level prevention modalities have not translated into population-level impact in southern Africa due to sub-optimal coverage among adolescents and youth who are hard to engage. We aim to investigate the feasibility, acceptability, and preliminary population level effectiveness of HIV prevention services with or without peer support to reduce prevalence of transmissible HIV amongst adolescents and young adults in KwaZulu-Natal. METHODS: We are conducting a 2 × 2 factorial trial among young men and women aged 16-29 years, randomly selected from the Africa Health Research Institute demographic surveillance area. Participants are randomly allocated to one of four intervention combinations: 1) Standard of Care (SOC): nurse-led services for HIV testing plus ART if positive or PrEP for those eligible and negative; 2) Sexual and Reproductive Health (SRH): Baseline self-collected vaginal and urine samples with study-organized clinic appointments for results, treatment and delivery of HIV testing, ART and PrEP integrated with SRH services; 3) Peer-support: Study referral of participants to a peer navigator to assess their health, social and educational needs and provide risk-informed HIV prevention, including facilitating clinic attendance; or 4) SRH + peer-support. The primary outcomes for effectiveness are: (1) the proportion of individuals with infectious HIV at 12 months and (2) uptake of risk-informed comprehensive HIV prevention services within 60 days of enrolment. At 12 months, all participants will be contacted at home and the study team will collect a dried blood spot for HIV ELISA and HIV viral load testing. DISCUSSION: This trial will enable us to understand the relative importance of SRH and peer support in creating demand for effective and risk informed biomedical HIV prevention and preliminary data on their effectiveness on reducing the prevalence of transmissible HIV amongst all adolescents and youth. TRIAL REGISTRATION: Trial Registry: clincialtrials.gov. CLINICALTRIALS: gov Identifier NCT04532307 . Registered: March 2020.

Process evaluation of peer-to-peer delivery of HIV self-testing and sexual health information to support HIV prevention among youth in rural KwaZulu-Natal, South Africa: qualitative analysis.

OBJECTIVE: Peer-to-peer (PTP) HIV self-testing (HIVST) distribution models can increase uptake of HIV testing and potentially create demand for HIV treatment and pre-exposure prophylaxis (PrEP). We describe the acceptability and experiences of young women and men participating in a cluster randomised trial of PTP HIVST distribution and antiretroviral/PrEP promotion in rural KwaZulu-Natal. METHODS: Between March and September 2019, 24 pairs of trained peer navigators were randomised to two approaches to distribute HIVST packs (kits+HIV prevention information): incentivised-peer-networks where peer-age friends distributed packs within their social network for a small incentive, or direct distribution where peer navigators distributed HIVST packs directly. Standard-of-care peer navigators distributed information without HIVST kits. For the process evaluation, we conducted semi-structured interviews with purposively sampled young women (n=30) and men (n=15) aged 18-29 years from all arms. Qualitative data were transcribed, translated, coded manually and thematically analysed using an interpretivist approach. RESULTS: Overall, PTP approaches were acceptable and valued by young people. Participants were comfortable sharing sexual health issues they would not share with adults. Coupled with HIVST, peer (friends) support facilitated HIV testing and solidarity for HIV status disclosure and treatment. However, some young people showed limited interest in other sexual health information provided. Some young people were wary of receiving health information from friends perceived as non-professionals while others avoided sharing personal issues with peer navigators from their community. Referral slips and youth-friendly clinics were facilitators to PrEP uptake. Family disapproval, limited information, daily pills and perceived risks were major barriers to PrEP uptake. CONCLUSION: Both professional (peer navigators) and social network (friends) approaches were acceptable methods to receive HIVST and sexual health information. Doubts about the professionalism of friends and overly exclusive focus on HIVST information materials may in part explain why HIVST kits, without peer navigators support, did not create demand for PrEP.

Early HIV treatment and survival over six years of observation in the ANRS 12249 Treatment as Prevention Trial.

OBJECTIVES: Population-based universal test and treat (UTT) trials have shown an impact on population-level virological suppression. We followed the ANRS 12249 TasP trial population for 6 years to determine whether the intervention had longer-term survival benefits. METHODS: The TasP trial was a cluster-randomized trial in South Africa from 2012 to 2016. All households were offered 6-monthly home-based HIV testing. Immediate antiretroviral therapy (ART) was offered through trial clinics to all people living with HIV (PLHIV) in intervention clusters and according to national guidelines in control clusters. After the trial, individuals attending the trial clinics were transferred to the public ART programme. Deaths were ascertained through annual demographic surveillance. Random-effects Poisson regression was used to estimate the effect of trial arm on mortality among (i) all PLHIV; (ii) PLHIV aware of their status and not on ART at trial entry; and (iii) PHLIV who started ART during the trial. RESULTS: Mortality rates among PLHIV were 9.3/1000 and 10.4/1000 person-years in the control and intervention arms, respectively. There was no evidence that the intervention decreased mortality among all PLHIV [adjusted rate ratio (aRR) = 1.10, 95% confidence interval (CI) = 0.85-1.43, p = 0.46] or among PLHIV who were aware of their status but not on ART. Among individuals who initiated ART, the intervention decreased mortality during the trial (aRR = 0.49, 95% CI = 0.28-0.85, p = 0.01), but not after the trial ended. CONCLUSIONS: The 'treat all' strategy reduced mortality among individuals who started ART but not among all PLHIV. To achieve maximum benefit of immediate ART, barriers to ART uptake and retention in care need to be addressed.

Prevalence of Mycobacterium tuberculosis in Sputum and Reported Symptoms Among Clinic Attendees Compared With a Community Survey in Rural South Africa.

BACKGROUND: Tuberculosis (TB) case finding efforts typically target symptomatic people attending health facilities. We compared the prevalence of Mycobacterium tuberculosis (Mtb) sputum culture-positivity among adult clinic attendees in rural South Africa with a concurrent, community-based estimate from the surrounding demographic surveillance area (DSA). METHODS: Clinic: Randomly selected adults (≥18 years) attending 2 primary healthcare clinics were interviewed and requested to give sputum for mycobacterial culture. Human immunodeficiency virus (HIV) and antiretroviral therapy (ART) status were based on self-report and record review. Community: All adult (≥15 years) DSA residents were invited to a mobile clinic for health screening, including serological HIV testing; those with ≥1 TB symptom (cough, weight loss, night sweats, fever) or abnormal chest radiograph were asked for sputum. RESULTS: Clinic: 2055 patients were enrolled (76.9% female; median age, 36 years); 1479 (72.0%) were classified HIV-positive (98.9% on ART) and 131 (6.4%) reported ≥1 TB symptom. Of 20/2055 (1.0% [95% CI, .6-1.5]) with Mtb culture-positive sputum, 14 (70%) reported no symptoms. Community: 10 320 residents were enrolled (68.3% female; median age, 38 years); 3105 (30.3%) tested HIV-positive (87.4% on ART) and 1091 (10.6%) reported ≥1 TB symptom. Of 58/10 320 (0.6% [95% CI, .4-.7]) with Mtb culture-positive sputum, 45 (77.6%) reported no symptoms. In both surveys, sputum culture positivity was associated with male sex and reporting >1 TB symptom. CONCLUSIONS: In both clinic and community settings, most participants with Mtb culture-positive sputum were asymptomatic. TB screening based only on symptoms will miss many people with active disease in both settings.

Antiretroviral therapy based HIV prevention targeting young women who sell sex: a mixed method approach to understand the implementation of PrEP in a rural area of KwaZulu-Natal, South Africa.

Pre-Exposure Prophylaxis (PrEP) is a potential game-changer for HIV. We used PrEP introduction for Young Women Who Sell Sex (YWSS) in a rural South Africa district to understand community norms and PrEP coverage in YWSS. Between 2017 and 2018, we measured awareness and uptake of PrEP in a representative cohort of 2184 Adolescent Girls and Young Women (AGYW) aged 13-22. We conducted group discussions with young people and community members (19); key informant interviews (9), in-depth interviews with 15-24 year-olds (58) and providers (33). Interviews were analysed using thematic analysis. PrEP awareness increased from 2% to 9%. Among 965 AGYW sexually-active by 2018, 13.4% (95%CI: 11.4%-15.7%) reported transactional sex and 10.6% (95%CI: 8.85-12.7%) sex for money. Of the 194 YWSS, 21 were aware of PrEP, but none had used it. Youth were enthusiastic about PrEP as tool for HIV prevention; whilst older community members were cautious about a technology they had limited experience with but could benefit select groups. Teachers and healthcare providers were concerned that PrEP would lower personal responsibility for sexual health. In conclusion, the narrow and limited introduction of PrEP to YWSS reduced the accessibility and reach. Introducing PrEP as part of sexual healthcare may improve demand and access for YWSS.

Evaluating the impact of DREAMS on HIV incidence among adolescent girls and young women: A population-based cohort study in Kenya and South Africa.

BACKGROUND: Through a multisectoral approach, the DREAMS Partnership aimed to reduce HIV incidence among adolescent girls and young women (AGYW) by 40% over 2 years in high-burden districts across sub-Saharan Africa. DREAMS promotes a combination package of evidence-based interventions to reduce individual, family, partner, and community-based drivers of young women's heightened HIV risk. We evaluated the impact of DREAMS on HIV incidence among AGYW and young men in 2 settings. METHODS AND FINDINGS: We directly estimated HIV incidence rates among open population-based cohorts participating in demographic and HIV serological surveys from 2006 to 2018 annually in uMkhanyakude (KwaZulu-Natal, South Africa) and over 6 rounds from 2010 to 2019 in Gem (Siaya, Kenya). We compared HIV incidence among AGYW aged 15 to 24 years before DREAMS and up to 3 years after DREAMS implementation began in 2016. We investigated the timing of any change in HIV incidence and whether the rate of any change accelerated during DREAMS implementation. Comparable analyses were also conducted for young men (20 to 29/34 years). In uMkhanyakude, between 5,000 and 6,000 AGYW were eligible for the serological survey each year, an average of 85% were contacted, and consent rates varied from 37% to 67%. During 26,395 person-years (py), HIV incidence was lower during DREAMS implementation (2016 to 2018) than in the previous 5-year period among 15- to 19-year-old females (4.5 new infections per 100 py as compared with 2.8; age-adjusted rate ratio (aRR) = 0.62, 95% confidence interval [CI] 0.48 to 0.82), and lower among 20- to 24-year-olds (7.1/100 py as compared with 5.8; aRR = 0.82, 95% CI 0.65 to 1.04). Declines preceded DREAMS introduction, beginning from 2012 to 2013 among the younger and 2014 for the older women, with no evidence of more rapid decline during DREAMS implementation. In Gem, between 8,515 and 11,428 AGYW were eligible each survey round, an average of 34% were contacted and offered an HIV test, and consent rates ranged from 84% to 99%. During 10,382 py, declines in HIV incidence among 15- to 19-year-olds began before DREAMS and did not change after DREAMS introduction. Among 20- to 24-year-olds in Gem, HIV incidence estimates were lower during DREAMS implementation (0.64/100 py) compared with the pre-DREAMS period (0.94/100 py), with no statistical evidence of a decline (aRR = 0.69, 95% CI 0.53 to 2.18). Among young men, declines in HIV incidence were greater than those observed among AGYW and also began prior to DREAMS investments. Study limitations include low study power in Kenya and the introduction of other interventions such as universal treatment for HIV during the study period. CONCLUSIONS: Substantial declines in HIV incidence among AGYW were observed, but most began before DREAMS introduction and did not accelerate in the first 3 years of DREAMS implementation. Like the declines observed among young men, they are likely driven by earlier and ongoing investments in HIV testing and treatment. Longer-term implementation and evaluation are needed to assess the impact of such a complex HIV prevention intervention and to help accelerate reductions in HIV incidence among young women.

Impact of the Covid-19 epidemic and related social distancing regulations on social contact and SARS-CoV-2 transmission potential in rural South Africa: analysis of repeated cross-sectional surveys.

BACKGROUND: South Africa implemented rapid and strict physical distancing regulations to minimize SARS-CoV-2 epidemic spread. Evidence on the impact of such measures on interpersonal contact in rural and lower-income settings is limited. METHODS: We compared population-representative social contact surveys conducted in the same rural KwaZulu-Natal location once in 2019 and twice in mid-2020. Respondents reported characteristics of physical and conversational ('close interaction') contacts over 24 hours. We built age-mixing matrices and estimated the proportional change in the SARS-CoV-2 reproduction number (R0). Respondents also reported counts of others present at locations visited and transport used, from which we evaluated change in potential exposure to airborne infection due to shared indoor space ('shared air'). RESULTS: Respondents in March-December 2019 (n = 1704) reported a mean of 7.4 close interaction contacts and 196 shared air person-hours beyond their homes. Respondents in June-July 2020 (n = 216), as the epidemic peaked locally, reported 4.1 close interaction contacts and 21 shared air person-hours outside their home, with significant declines in others' homes and public spaces. Adults aged over 50 had fewer close contacts with others over 50, but little change in contact with 15-29 year olds, reflecting ongoing contact within multigenerational households. We estimate potential R0 fell by 42% (95% plausible range 14-59%) between 2019 and June-July 2020. CONCLUSIONS: Extra-household social contact fell substantially following imposition of Covid-19 distancing regulations in rural South Africa. Ongoing contact within intergenerational households highlighted a potential limitation of social distancing measures in protecting older adults.

Thetha Nami: participatory development of a peer-navigator intervention to deliver biosocial HIV prevention for adolescents and youth in rural South Africa.

BACKGROUND: Despite effective biomedical tools, HIV remains the largest cause of morbidity/mortality in South Africa - especially among adolescents and young people. We used community-based participatory research (CBPR), informed by principles of social justice, to develop a peer-led biosocial intervention for HIV prevention in KwaZulu-Natal (KZN). METHODS: Between March 2018 and September 2019 we used CBPR to iteratively co-create and contextually adapt a biosocial peer-led intervention to support HIV prevention. Men and women aged 18-30 years were selected by community leaders of 21 intervention implementation areas (izigodi) and underwent 20 weeks of training as peer-navigators. We synthesised quantitative and qualitative data collected during a 2016-2018 study into 17 vignettes illustrating the local drivers of HIV. During three participatory intervention development workshops and community mapping sessions, the peer-navigators critically engaged with vignettes, brainstormed solutions and mapped the components to their own izigodi. The intervention components were plotted to a Theory of Change which, following a six-month pilot and process evaluation, the peer-navigators refined. The intervention will be evaluated in a randomised controlled trial ( NCT04532307 ). RESULTS: Following written and oral assessments, 57 of the 108 initially selected participated in two workshops to discuss the vignettes and co-create the Thetha Nami (`talk to me'). The intervention included peer-led health promotion to improve self-efficacy and demand for HIV prevention, referrals to social and educational resources, and aaccessible youth-friendly clinical services to improve uptake of HIV prevention. During the pilot the peer-navigators approached 6871 young people, of whom 6141 (89%) accepted health promotion and 438 were linked to care. During semi-structured interviews peer-navigators described the appeal of providing sexual health information to peers of a similar age and background but wanted to provide more than just "onward referral". In the third participatory workshop 54 peer-navigators refined the Thetha Nami intervention to add three components: structured assessment tool to tailor health promotion and referrals, safe spaces and community advocacy to create an enabling environment, and peer-mentorship and navigation of resources to improve retention in HIV prevention. CONCLUSION: Local youth were able to use evidence to develop a contextually adapted peer-led intervention to deliver biosocial HIV prevention.

Convergence of infectious and non-communicable disease epidemics in rural South Africa: a cross-sectional, population-based multimorbidity study.

BACKGROUND: There has been remarkable progress in the treatment of HIV throughout sub-Saharan Africa, but there are few data on the prevalence and overlap of other significant causes of disease in HIV endemic populations. Our aim was to identify the prevalence and overlap of infectious and non-communicable diseases in such a population in rural South Africa. METHODS: We did a cross-sectional study of eligible adolescents and adults from the Africa Health Research Institute demographic surveillance area in the uMkhanyakude district of KwaZulu-Natal, South Africa. The participants, who were 15 years or older, were invited to participate at a mobile health camp. Medical history for HIV, tuberculosis, hypertension, and diabetes was established through a questionnaire. Blood pressure measurements, chest x-rays, and tests of blood and sputum were taken to estimate the population prevalence and geospatial distribution of HIV, active and lifetime tuberculosis, elevated blood glucose, elevated blood pressure, and combinations of these. FINDINGS: 17 118 adolescents and adults were recruited from May 25, 2018, to Nov 28, 2019, and assessed. Overall, 52·1% (95% CI 51·3-52·9) had at least one active disease. 34·2% (33·5-34·9) had HIV, 1·4% (1·2-1·6) had active tuberculosis, 21·8% (21·2-22·4) had lifetime tuberculosis, 8·5% (8·1-8·9) had elevated blood glucose, and 23·0% (22·4-23·6) had elevated blood pressure. Appropriate treatment and optimal disease control was highest for HIV (78·1%), and lower for elevated blood pressure (42·5%), active tuberculosis (29·6%), and elevated blood glucose (7·1%). Disease prevalence differed notably by sex, across age groups, and geospatially: men had a higher prevalence of active and lifetime tuberculosis, whereas women had a substantially high prevalence of HIV at 30-49 years and an increasing prevalence of multiple and poorly controlled non-communicable diseases when older than 50 years. INTERPRETATION: We found a convergence of infectious and non-communicable disease epidemics in a rural South African population, with HIV well treated relative to all other diseases, but tuberculosis, elevated blood glucose, and elevated blood pressure poorly diagnosed and treated. A public health response that expands the successes of the HIV testing and treatment programme to provide multidisease care targeted to specific populations is required to optimise health in such settings in sub-Saharan Africa. FUNDING: Wellcome Trust, Bill & Melinda Gates Foundation, the South African Department of Science and Innovation, South African Medical Research Council, and South African Population Research Infrastructure Network. TRANSLATION: For the isiZulu translation of the abstract see Supplementary Materials section.