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Although deep learning algorithms show increasing promise for disease diagnosis, their use with rapid diagnostic tests performed in the field has not been extensively tested. Here we use deep learning to classify images of rapid human immunodeficiency virus (HIV) tests acquired in rural South Africa. Using newly developed image capture protocols with the Samsung SM-P585 tablet, 60 fieldworkers routinely collected images of HIV lateral flow tests. From a library of 11,374 images, deep learning algorithms were trained to classify tests as positive or negative. A pilot field study of the algorithms deployed as a mobile application demonstrated high levels of sensitivity (97.8%) and specificity (100%) compared with traditional visual interpretation by humans—experienced nurses and newly trained community health worker staff—and reduced the number of false positives and false negatives. Our findings lay the foundations for a new paradigm of deep learning–enabled diagnostics in low- and middle-income countries, termed REASSURED diagnostics 1 , an acronym for real-time connectivity, ease of specimen collection, affordable, sensitive, specific, user-friendly, rapid, equipment-free and deliverable. Such diagnostics have the potential to provide a platform for workforce training, quality assurance, decision support and mobile connectivity to inform disease control strategies, strengthen healthcare system efficiency and improve patient outcomes and outbreak management in emerging infections. In a pilot field study conducted in rural South Africa, deep learning algorithms can accurately classify rapid HIV tests as positive or negative, highlighting the potential of deep learning–enabled diagnostics for use in low- and middle-income countries.

Sexually transmitted infections (STIs) and bacterial vaginosis (BV) are associated with increased transmission of HIV, and poor reproductive and sexual health. The burden of STIs/BV among young people is unknown in many high HIV prevalence settings. We conducted an acceptability, feasibility, and prevalence study of home-based sampling for STIs/BV among young men and women aged 15-24 years old in a health and demographic surveillance site (HDSS) in rural KwaZulu-Natal, South Africa. A total of 1,342 young people, stratified by age (15-19 and 20-24 years) and sex were selected from the HDSS sampling frame; 1,171/1,342 (87%) individuals had ≥1 attempted home visit between 4 October 2016 and 31 January 2017, of whom 790 (67%) were successfully contacted. Among the 645 who were contacted and eligible, 447 (69%) enrolled. Consenting/assenting participants were interviewed, and blood, self-collected urine (men), and vaginal swabs (women) were tested for herpes simplex virus type 2 (HSV-2), chlamydia, gonorrhoea, syphilis, trichomoniasis, and BV. Both men and women reported that sample collection was easy. Participants disagreed that sampling was painful; more than half of the participants disagreed that they felt anxious or embarrassed. The weighted prevalence of STIs/BV among men and women, respectively, was 5.3% and 11.2% for chlamydia, 1.5% and 1.8% for gonorrhoea, 0% and 0.4% for active syphilis, 0.6% and 4.6% for trichomoniasis, 16.8% and 28.7% for HSV-2, and 42.1% for BV (women only). Of the women with ≥1 curable STI, 75% reported no symptoms. Factors associated with STIs/BV included having older age, being female, and not being in school or working. Among those who participated in the 2016 HIV serosurvey, the prevalence of HIV was 5.6% among men and 19% among women. Feasibility was impacted by the short study duration and the difficulty finding men at home. A high prevalence of STIs/BV was found in this rural setting with high HIV prevalence in South Africa. Most STIs and HIV infections were asymptomatic and would not have been identified or treated under national syndromic management guidelines. A nested STI/BV survey within a HDSS proved acceptable and feasible. This is a proof of concept for population-based STI surveillance in low- and middle-income countries that could be utilised in the evaluation of STI/HIV prevention and control programmes.

Adolescent girls and young women (AGYW) bear the brunt of the HIV epidemic in South Africa. 'DREAMS' aims to reduce HIV incidence through multi-level combination prevention. We describe HIV incidence and uptake of HIV and sexual reproductive health (SRH) by AGYW in KwaZulu-Natal (KZN), prior to DREAMS. Longitudinal and cross-sectional analysis of women (15-24 year old) in a population-based HIV incidence cohort within a demographic surveillance site in KZN. Observation time for HIV incidence was person-years at risk while resident. \"Current use of contraceptives\" and \"having an HIV test in the past 12 months\" was compared between 2011 and 2015. In 2015, HIV prevalence was 11.0% and 34.1% and HIV incidence (2011-2015) was 4.54% (95%CI:3.89-5.30) and 7.45% (95%CI:6.51-8.51) per year in 15-19 and 20-24 year olds respectively, with no significant decline compared to 2006-2010. In 2015, 90.7% of 20-24-year-olds were unemployed, 36.4% and 51.7% of 15-19 and 20-24 year olds reported recent migration; 20.9% and 72.6% of 15-19 and 20-24 year olds had ever been pregnant. In 2015, less than 50% reported condom-use at last sex, 15.0% of 15-19 year olds and 48.9% of 20-24 year olds were currently using contraception and 32.0% and 66.7% of 15-19 and 20-24 year olds had tested for HIV in the past 12 months. There had been no improvement compared to 2011. Factors associated with AGYW testing for HIV in the past 12 months were, survey year-2011 more likely than 2015 (aOR = 0.50), number of partners (aOR = 3.25), ever been pregnant (aOR = 2.47) and knowing where to find ART (aOR = 1.54). Factors associated with contraception use were being older (aOR = 4.83); ever been pregnant (aOR = 12.62); knowing where to get ART (aOR = 1.79) and having had an HIV test in past 12 months (aOR = 1.74). Prior to DREAMS, HIV incidence in AGYW was high. HIV and SRH service uptake did not improve and was suboptimal. Findings highlight the need for combination HIV prevention programmes for AGYW in this economically vulnerable area.

This study aimed to identify the interrelationships between mature BDNF (mBDNF), precursor BDNF (proBDNF) trajectories, and cognitive performance in individuals with HIV from sub-Saharan Africa over 96 weeks following antiretroviral therapy (ART) initiation. Using data from 154 participants in the ACTG 5199 study (ClinicalTrials.gov NCT00096824, 2005-06-23) in Johannesburg and Harare (2006–2009), we measured serum mBDNF and proBDNF levels via ELISA and assessed cognitive performance with neuropsychological tests. Group-based trajectory modelling indicated two mBDNF trajectories—“Stable Ascent” (83.9%) and “Peak with Gradual Decline” (16.1%)—and two proBDNF trajectories—“Gradual Increase” (85.7%) and “Gradual Decline” (14.3%). These were linked to three cognitive trajectories: “Low Baseline-Slow Improvement,” “Gradual Improvement,” and “Late Surge.” The “Stable Ascent” mBDNF group showed a significant probability of “Gradual Improvement” (68%) in cognitive performance and a “Late Surge” (9.5%). In contrast, the “Peak with Gradual Decline” mBDNF trajectory saw no “Late Surge.” A “Gradual Increase” in proBDNF corresponded to a 67.7% chance of “Gradual Improvement” in cognition. Findings suggest BDNF isoforms as potential biomarkers for cognitive interventions in HIV, emphasizing that stable or increasing BDNF levels post-ART are linked to favourable cognitive outcomes. Further research is needed to develop BDNF-based cognitive health strategies to improve outcomes for people with HIV.

Young men are less likely than young women to engage with HIV prevention and care, and their HIV-related mortality is higher. We describe HIV incidence and uptake of HIV services in men 20-29 years(y) in rural KwaZulu-Natal, South Africa, before the roll-out of DREAMS. We used data from a population-based demographic and HIV surveillance cohort. HIV incidence was estimated from anonymised testing in an annual serosurvey. Service uptake was assessed in 2011 and 2015, through two self-reported outcomes: 1) HIV testing in the past 12 months(m); 2) voluntary medical male circumcision(VMMC). Logistic regression was used to estimate odds ratios(OR) and 95% confidence intervals(CI) for factors associated with each outcome. HIV incidence in 2011-2015 was 2.6/100 person-years (95%CI = 2.0-3.4) and 4.2 (95%CI = 3.1-5.6) among men 20-24y and 25-29y, respectively, with no significant change from 2006-2010. N = 1311 and N = 1221 young men participated in the 2011 and 2015 surveys, respectively. In both years, <50% reported testing for HIV in the past 12m. In 2011, only 5% reported VMMC, but coverage in 2015 increased to 40% and 20% in men 20-24y and 25-29y, respectively. HIV testing was positively associated with higher education and mobility. Testing uptake was higher in men reporting >1 partner in the past 12m, or condom use at last sex, but lower in those reporting a casual partner (adjusted (a)OR = 0.53, 95%CI = 0.37-0.75). VMMC uptake was associated with survey year and higher education. Men aged 25-29y and those who were employed (aOR = 0.66; 95%CI = 0.49-0.89) were less likely to report VMMC. HIV incidence in men 20-29y was very high, and pre-exposure prophylaxis (PrEP) should be considered in this population. Uptake of services was low. VMMC coverage increased dramatically from 2011 to 2015, especially among younger men, suggesting a demand for this service. Interventions designed with and for young men are urgently needed.

Introduction Despite the efficacy of antiretroviral therapy (ART)‐based prevention, population‐level impact remains limited because those at high risk of HIV acquisition are not reached by conventional services. We investigated whether youth‐centred and tailored HIV prevention, delivered by community‐based peer navigators alongside sexual and reproductive health (SRH) services, can mobilize demand for HIV pre‐exposure prophylaxis (PrEP) and ART among adolescents and young adults (AYA) in KwaZulu‐Natal, South Africa. Methods Thetha Nami ngithethe nawe is a cluster‐randomized stepped‐wedge trial (SWT) in 40 clusters within a rural health and demographic surveillance site. Clusters were randomized to receive the intervention in period 1 (early) or period 2 (delayed). Trained area‐based peer navigators conducted needs assessments with youth aged 15–30 years to tailor health promotion, psychosocial support and referrals into nurse‐led mobile SRH clinics that also provided HIV testing, and status‐neutral ART and oral PrEP. Standard of care was PrEP delivered through primary health clinics. We report SRH service uptake from the 20 intervention clusters during the first period of the SWT (NCT05405582). Results Between June 2022 and September 2023, peer‐navigators reached 9742 (74.9%) of the 13,000 youth in the target population, 46.8% males. Among 9576 individuals with needs assessment, peer‐navigators identified 141 (1.5%) with social needs, and 4138 (43.5%) had medium to high health needs. These individuals were referred to mobile clinics, with 2269 (54.8%) attending, including 959 (42.3%) males. HIV testing uptake was high (92.7%; 2103/2269), with 10.1% (212/2103) testing positive for HIV, 62 (29.2%) of whom started ART for the first time. The prevalence of HIV was higher among females compared to males (15.1% vs. 3.3%; p < 0.001). Among clinic attendees, 96.8% were screened for PrEP eligibility, with 38.5% deemed eligible and offered PrEP. Of the 1433 (63.2%) individuals tested for sexually transmitted infections (STIs), 418 (29.2%) tested positive, with females having higher STI prevalence (37.2% vs. 17.9%; p < 0.001). Of these, 385 (92.1%) received STI treatment. Among 1310 females, 769 (58.7%) reported not using any contraception at their initial visit, and 275/769 (35.8%) started contraception during the trial. Conclusions Community‐based and person‐centred approaches delivered through trained peer‐navigators can link AYA with SRH and HIV prevention/care needs with mobile SRH services.

Introduction Differentiated service delivery (DSD) models for HIV and tuberculosis (TB) care prioritize efficient resource allocation and targeted interventions, and benefit from accurate assessment of patients’ antiretroviral therapy (ART) pill‐taking status. Accurate ART use identification is essential for ensuring proper care transition services rather than unnecessary initiation. A point‐of‐care urine tenofovir (TFV) assay may identify undisclosed ART use in settings with high rates of TB and HIV coinfection. Methods A cohort of people living with HIV (PWH) presenting for routine care, including newly diagnosed and those returning to care, and reporting no ART use within 90 days, was enrolled in a clinic‐based cross‐sectional study of TB prevalence which tested for TB using sputum and urine‐based TB tests in two clinics in KwaZulu‐Natal, South Africa. CD4 counts were determined at the time of ART initiation, per national guidelines. A novel urine‐based lateral flow assay (LFA) which detects TFV ingested within the past 4–7 days was used to assess ART use from thawed urine samples, which were collected concurrently with the self‐report assessment. Conditional logistic regression models assessed predictors of ART non‐disclosure. Results Between 12/2021 and 5/2024, 404 PWH (40% male) reporting no recent ART use presented for ART initiation. TB testing identified 14 (3%) PWH with undiagnosed TB. Seventy‐nine (20%) had detectable TFV in urine indicating undisclosed ART use, with a median CD4 count of 466 cells/mm3 (IQR 277–625) compared to 322 cells/mm3 (IQR 175–490, p = 0.001) in those without undisclosed ART use. In a multivariable model, undisclosed ART use was associated with older age, rural clinic site, higher CD4 count and having active TB, but not with gender, education or employment. Conclusions Among people presenting for HIV treatment initiation, 20% had evidence of ART use within 4–7 days by TFV urine LFA testing. Integration of point‐of‐care urine TFV assays into DSD models of HIV care may support providers to engage PWH about treatment challenges, address potential barriers to disclosure and facilitate seamless transfers between clinics. If successful, this strategy may reduce duplicative care entries and promote more efficient use of resources.

ObjectiveTo 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).DesignOne longitudinal and three cross-sectional surveys of representative samples of AGYW.SettingAGYW in four South African districts with high HIV prevalence (>10%) (May 2017 and September 2019).Participants6311 AGYW aged 12–24.MeasuresUsing 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.ResultsWithin 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.ConclusionsAmong 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.

The polyvalent African horsesickness (AHS) attenuated live virus (AHS-ALV) vaccine produced at Onderstepoort Biological Products incorporates 7 of the 9 known serotypes circulating in southern Africa. Serological cross-reaction has been shown in vitro to Serotypes 5 and 9 by Serotypes 8 and 6 respectively, but the degree of in vivo cross-protection between these serotypes in vaccinated horses has not previously been reported. Due to the increasing incidence of AHS Serotypes 5 and 9 in the field, over the last 3–4 seasons of AHS in South Africa, and the absence of Serotypes 5 and 9 in the AHS-ALV vaccine, it was necessary to conduct a vaccination-challenge study to determine in vivo cross-protection of vaccine-incorporated Serotypes 8 and 6 respectively. Groups of horses were vaccinated with either the polyvalent AHS-ALV vaccine or a monovalent Serotype 6 (vAHSV6) or 8 (vAHSV8) vaccine to determine the cross-protection of vaccinated horses following challenge with virulent AHS virus (AHSV) of either Serotype 5, 6, 8 or 9. Serial vaccination of naive horses with the polyvalent AHS-ALV vaccine generated a broad neutralizing antibody response to all vaccine strains as well as cross-neutralizing antibodies to Serotypes 5 and 9. Booster vaccination of horses with monovalent vaccine vAHSV6 or vAHSV8 induced an adequate protective immune response to challenge with homologous and heterologous virulent virus. In vivo cross-protection between AHSV6 and AHSV9 and AHSV8 and AHSV5 respectively, was demonstrated.

Study objectiveWe investigated two peer distribution models of HIV self-testing (HIVST) in HIV prevention demand creation compared with trained young community members (peer navigators).MethodsWe used restricted randomisation to allocate 24 peer navigator pairs (clusters) in KwaZulu-Natal 1:1:1: (1) standard of care (SOC): peer navigators distributed clinic referrals, pre-exposure prophylaxis (PrEP) and antiretroviral therapy (ART) information to 18–30 year olds. (2) peer navigator direct distribution (PND): Peer navigators distributed HIVST packs (SOC plus two OraQuick HIVST kits) (3) incentivised peer networks (IPN): peer navigators recruited young community members (seeds) to distribute up to five HIVST packs to 18–30 year olds within their social networks. Seeds received 20 Rand (US$1.5) for each recipient who distributed further packs. The primary outcome was PrEP/ART linkage, defined as screening for PrEP/ART eligibility within 90 days of pack distribution per peer navigator month (pnm) of outreach, in women aged 18–24 (a priority for HIV prevention). Investigators and statisticians were blinded to allocation. Analysis was intention to treat. Total and unit costs were collected prospectively.ResultsBetween March and December 2019, 4163 packs (1098 SOC, 1480 PND, 1585 IPN) were distributed across 24 clusters. During 144 pnm, 272 18–30 year olds linked to PrEP/ART (1.9/pnm). Linkage rates for 18–24-year-old women were lower for IPN (n=26, 0.54/pnm) than PND (n=45, 0.80/pnm; SOC n=49, 0.85/pnm). Rate ratios were 0.68 (95% CI 0.28 to 1.66) for IPN versus PND, 0.64 (95% CI 0.26 to 1.62) for IPN versus SOC and 0.95 (95% CI 0.38 to 2.36) for PND versus SOC. In 18–30 year olds, PND had significantly more linkages than IPN (2.11 vs 0.88/pnm, RR 0.42, 95% CI 0.18 to 0.98). Cost per pack distributed was cheapest for IPN (US$36) c.f. SOC (US$64). Cost per person linked to PrEP/ART was cheaper in both peer navigator arms compared with IPN.DiscussionHIVST did not increase demand for PrEP/ART. Incentivised social network distribution reached large numbers with HIVST but resulted in fewer linkages compared with PrEP/ART promotion by peer navigators.Trial registration number NCT03751826.