Desmond Tutu HIV Foundation

Analyzing gene expression data from three separate clinical trials, we find that the antiretroviral drug tenofovir, which belongs to the class of nucleotide analogue reverse transcriptase inhibitors, induces the type I/III interferon system of innate immunity in the mucosa. This effect occurs in the absence of HIV infection and manifests itself over various treatment durations and after both oral and topical drug delivery. Tenofovir and other related medications are important components of long-term antiretroviral treatment taken by people living with HIV. Therefore, this unexpected immunological effect might need to be considered as a potential contributor to comorbidities in people living with HIV, as well as an immunopharmacological co-factor when testing novel HIV cure interventions. This study is registered with ClinicalTrials.gov as NCT01768962, NCT01687218, and NCT01232803.

Despite known maternal, perinatal, and infant health risks of tuberculosis during pregnancy, global estimates of incidence remain scarce. Existing estimates are outdated, and do not include the postpartum period, HIV co-infection, age, or specific changes in risk, limiting our understanding of the true scale of disease in this understudied population. In this rapid review and modelling analysis, we estimated the global tuberculosis incidence in pregnant and postpartum women using a population-based modelling approach. We searched MEDLINE and EMBASE, with no date or language limits, and included studies reporting tuberculosis incidence in pregnancy or postpartum with suitable comparison groups; we also used Feb 6, 2025, interim data from the ongoing ORCHID cohort. We combined WHO age and sex-stratified tuberculosis incidence data with country-specific population and fertility data to estimate baseline tuberculosis incidence, and applied systematic review-based risk ratios to account for elevated increased risk during pregnancy and postpartum. Uncertainty in all inputs was propagated using standard error propagation formulae and summarised as mean tuberculosis incidence rates and mean incidence rate ratios (IRRs), each reported with 95% quantile-based uncertainty intervals (UIs). We identified 37 studies published between 1996 and 2020, of which three were of sufficient quality to provide data for HIV-negative women. One additional study (ORCHID; Odayar et al, unpublished) provided data for women living with HIV. Compared with non-pregnant women without HIV, tuberculosis IRRs were 1·34 (95% CI 1·17-1·54) during pregnancy and 1·91 (1·53-2·39) during postpartum among HIV-negative women. For women living with HIV, IRRs were 5·73 (95% CI 2·64-10·94) during pregnancy and 3·58 (0·85-9·63) postpartum. We estimated 239 500 pregnant women (95% UI 216 300-262 800) and 97 600 postpartum women (90 100-105 200) developed tuberculosis disease globally in 2023, with HIV contributing to 21·3% (19·8-22·8) and 10·6% (9·9-11·3) of cases, respectively. The WHO African region had the highest incidence (110 600 [95% UI 96 700-124 500] in pregnant women and 40 900 [36 300-45 400] in postpartum women), followed by the South-East Asia region (79 900 [64 100-95 700] in pregnant women and 35 900 [30 800-41 100] in postpartum women). Pregnant and postpartum women face substantial tuberculosis risk, yet remain under-represented in global estimates. Our findings underscore the need for improved surveillance and targeted interventions to reduce tuberculosis incidence in this group. UK Medical Research Council.

ABSTRACT This study investigated the spatial distribution of HIV testing and antiretroviral therapy initiation among adolescents and youth in rural KwaZulu-Natal, South Africa, to inform the optimal allocation of HIV services. The sample included 5,352 participants aged 13–35 years from nested cohort studies within Africa’s largest population-based prospective cohorts, with global positioning system data collected for all homesteads. HIV testing prevalence and ART initiation prevalence were mapped using a kernel density approach, and socio-demographic correlates were examined using multivariable regression. Kernel density mapping revealed substantial geographic disparities in HIV testing and ART initiation. Multivariable analysis showed that tertiary education (aβ: 4.53; 95% CI: 2.11, 6.88), rural residence (aβ: −31.14; 95% CI: −32.32, −29.65), and living within 3 km of a health facility (aβ: −2.42; 95% CI: −3.88, −0.96) were associated with HIV testing prevalence. ART initiation prevalence was associated with rural residence (aβ: −5.44; 95% CI: -7.38, -3.37), participation in HIV self-testing (aβ: 3.21; 95% CI: 0.64, 5.80), and lack of participation in STI screening and treatment (aβ: −1.22; 95% CI: −2.44, −0.03). Our research underscores the urgent need for addressing geographical access to HIV testing and treatment uptake amongst adolescents and youth in rural communities, and promoting HIV self-testing.

Tuberculosis (TB) patients who are diagnosed but not registered and initiated on TB treatment are categorised as initial loss to follow-up (ILTFU). ILTFU is a key driver of morbidity and mortality associated with TB and is a contributing factor to high TB transmission rates. LINKEDin was a quasi-experimental study which evaluated two specific interventions for reducing ILTFU in three high-TB burden provinces in South Africa, conducted from October 2018 to December 2020. As part of LINKEDin, we undertook a micro-costing from the healthcare provider perspective using an activity-based costing approach. Cost estimates included the cost of the operation of an integrated provincial health data centre in the Western Cape, apportioned to the TB activities it supported in the province. Cost estimates were linked to intervention outcomes to understand the incremental cost of the intervention per additional patient linked to care compared to rates of ILTFU in the absence of the interventions. Sensitivity analyses were conducted to account for uncertainty in the intervention outcomes, and for periods where the implementation of the intervention was interrupted due to COVID-19 related disruptions. Costing data were collected between August 2020 and March 2021. The total cost of implementing the LINKEDin intervention in the WC and KZN was $7 534.42 per month. The cost of implementing LINKEDin in the Western Cape accounted for 56% the total cost of the intervention - 8% from the operations of the PHDC and 48% from the cost of running the intervention - while only 44% of the total cost was accounted for by the intervention run in KwaZulu-Natal. The primary cost driver of the interventions were staff salaries, with the cost of data extraction and in-hospital activities low relative to primary healthcare (PHC)-based follow-up activities. In terms of cost effectiveness, the LINKEDin interventions in KZN was cost $377.28 per additional person linked to care, and $243.62 in the WC, per additional person linked to care. In the Western Cape, systematically tracking persons with TB using an automated system proved highly cost efficient compared to the more labour intense approach adopted in KwaZulu-Natal. Optimising the curation and management of data and increasing the effectiveness of tracing systems and processes can result in cost-savings.

The risk of HIV acquisition is heightened during pregnancy and early parenthood with the additional risk of vertical HIV transmission. While recent studies have improved our understanding of PrEP use among pregnant and breastfeeding women, further evidence is needed to inform the design of interventions that support sustained use, especially among young women who are pregnant or parenting. We analysed data from young women aged 15-29 years who initiated PrEP in an implementation study (FastPrEP) in Cape Town, South Africa. Logistic regression was used to examine the association between pregnancy or parenting status (≥ 1 living child) and PrEP discontinuation at 1- and 4-months post-initiation, based on pharmacy refill data. The primary exposure was currently pregnant or having a child (vs. not); secondary analyses stratified by age (15-24 vs. 25-29 years) among women who were pregnant/parenting. Models were adjusted for age and hypothesised explanatory factors were included in sensitivity analysis: service delivery location, contraceptive use, HIV risk perception, and relationship status. Between August 2022 and June 2024 n = 4,876 young women initiated PrEP; 44% were pregnant/parenting (of which 10% were pregnant), and the median age was 21.6 years (IQR:18-25). At 1-month, women who were pregnant/parenting had higher odds of PrEP discontinuation (aOR:1.30, 95% CI:1.14-1.49). At 4-months this relationship persisted (aOR:1.41, 95% CI:1.12-1.78) compared with non-pregnant/parenting women. Among those pregnant/parenting, younger women (15-24 years) had higher odds of discontinuation at 1-month (aOR:1.31, 95% CI:1.08-1.58) and 4-months (aOR:1.41, 95%CI:1.02-1.96) compared to women aged 25-29. In the fully adjusted multivariable model, receiving PrEP in mobile clinics (aOR:0.71, 95% CI:0.61-0.82) vs. government clinics was associated with lower odds of early discontinuation. Young women who are pregnant/parenting face elevated risk of early PrEP discontinuation. Differentiated, life-stage and youth-responsive interventions, such as counselling, partner involvement, and integration with maternal and child health, or sexual and reproductive health services, are critical to improving PrEP persistence among this priority population. This population should be prioritised in the rollout of long-acting PrEP formulations, which may better align with their needs and reduce the burden of daily adherence.

Background. Transgender and gender-diverse (TGD) people face significant discrimination in the South African (SA) health system, limiting their access to HIV services and gender-affirming care, which supports an individual’s gender identity when it does not align with their sex assigned at birth. Despite the critical role of these services for TGD people, access to care remains understudied in SA. Objectives. To describe TGD people and their access to and need for social, legal and medical transition, including psychosocial care, hormone therapy and surgery, as well as HIV services, in the Eastern Cape and Western Cape provinces, South Africa. Methods. A cross-sectional quantitative survey design was utilised, with 150 TGD individuals recruited via convenience sampling in the Western and Eastern Cape provinces. Interviews were conducted using structured questionnaires, with data captured on REDCap. Descriptive analysis was conducted using Stata 18. Results. Of the 150 respondents, 74.0% were people assigned male at birth (AMAB) and 26.0% were people assigned female at birth (AFAB). Reported gender identities showed that 68.5% of AMAB respondents identified as transgender women/female, 56.4% of AFAB respondents identified as transgender men/male and 34.0% of all respondents identified as gender diverse or non-binary. Demographics showed a vulnerable population, with 18.7% with housing insecurity and 66.0% unemployed. While social transition was common (98.7%), access to legal transition (4.0%) was very low, as was access to all forms of medical gender-affirming care, with 44.7% of TGD people accessing psychosocial care, 32.0% accessing hormone therapy and 2.7% surgery. Of the respondents who had not legally transitioned, 71.4% wanted to. Most respondents who had not accessed medical gender-affirming care services expressed a need for psychosocial care (77.1%) and hormone therapy (68.6%). Gender-affirming surgery was more variable, with 33.3% of AFAB respondents wanting bottom surgery compared with top surgery (63.9%), and 49.5% of AMAB respondents wanting bottom surgery compared with top surgery (55.9%). Almost all (99.3%) respondents had had an HIV test in their lifetime, with reported HIV prevalence differing between AMAB (34.2%) and AFAB (7.9%) respondents. PrEP uptake among HIV-negative AMAB respondents was 30.4%, and 5.7% among AFAB respondents, while 78.0% of TGD people living with HIV were on antiretroviral treatment. Conclusion. Findings demonstrate a critical gap between needed and actual access to legal and medical gender-affirming care services. There is an urgent need for the provision of integrated and accessible gender-affirming care and HIV services as part of comprehensive care for TGD populations within inclusive health systems nationally.

ABSTRACT Oral liquid formulations of zidovudine (ZDV) and nevirapine (NVP) are the main antiretrovirals (ARVs) for neonates born to mothers living with HIV, but they have limitations including poor palatability, short shelf-life, frequent dosing and supply challenges. Understanding caregiver and provider preferences for infant ARV formulations is essential to guide the development of acceptable alternatives. Within the PETITE-DTG trial in South Africa (NCT05590325), evaluating the pharmacokinetics, safety and acceptability of novel dolutegravir (DTG) formulations in neonates, we explored ARV preferences among mothers (n = 28) and health workers (n = 6). Participants completed interviews ranking six formulations: existing ZDV and NVP syrups, a DTG dispersible tablet (DTG-DT), a novel DTG oral dispersible film (DTG-film) and two pipeline options (long-acting injectable; transdermal patch). Both groups strongly favoured DTG-film, highlighting ease of administration, confidence in accurate dosing and discreetness. Long-acting injectables were next preferred, viewed as convenient despite concerns about discomfort. DTG-DT, ZDV and NVP ranked lower due to preparation challenges and risk of spillage. Transdermal patches were least favoured, with concerns regarding the comfort of neonates, impact of water exposure and effectiveness. These findings underscore strong support for innovative ARV options, emphasizing usability, ease of administration and reduced dosing frequency for the treatment of neonates.

Problematic substance use is associated with poor HIV clinical outcomes, including among adolescents and young adults (AYAs) living with HIV. Higher levels of potentially problematic substance use among those diagnosed with HIV during the COVID-19 pandemic may have been mediated by declining levels of social capital and varied depending on an individual's level of anticipated stigma. We sought to determine whether social capital mediates the relationship between time of HIV diagnosis (pre- versus intra-pandemic) and potentially problematic substance use as a function of anticipated stigma. This moderated mediation analysis utilized baseline data from two demographically similar cohorts of young South Africans ages 18-24years who tested positive for HIV either before or during the COVID-19 pandemic. The relationships between time of diagnosis in relation to the COVID-19 pandemic, social capital, potentially problematic substance use, and anticipated stigma were analyzed using a series of logistic regression, mediation, and moderated mediation analyses. Compared to their peers diagnosed before the pandemic, young people diagnosed during the COVID-19 pandemic were more likely to screen positive for potentially problematic substance use (OR 3.561; CI 1.827, 6.943; p < 0.001). Social capital was an inconsistent mediator of the relationship between time of diagnosis and potentially problematic substance use, such that lower social support observed among those diagnosed during the COVID-19 pandemic partially suppressed the positive association between pandemic time of diagnosis and potentially problematic substance use (indirect effect = -0.363; CI -0.717, -0.119). There was a significant moderated mediation effect of anticipated stigma (index of moderated mediation = 0.028; CI 0.03, 0.061), indicating that the negative indirect effect of time of diagnosis on potentially problematic substance use weakened at higher levels of anticipated stigma. Diagnosis during the COVID-19 pandemic was associated with a greater likelihood of screening positive for potentially problematic substance use. Although those diagnosed during the pandemic reported lower social capital, social capital was itself associated with potentially problematic substance use. However, this association weakened at high levels of anticipated stigma. These findings may suggest that diagnosis during the pandemic may have exposed those with higher social capital to social networks and norms conducive to substance use, underscoring the need for longitudinal research and interventions addressing the social contexts shaping substance use in this population. Some data from this study emanate from a pilot randomized controlled trial, which was prospectivelyregistered at ClinicalTrials.gov (Identifier: NCT04568460) prior to participant enrollment.

Abstract Three Interlinked Electronic Register (TIER.Net) is South Africa’s national electronic HIV patient database, used to monitor antiretroviral therapy (ART) delivery and laboratory results. However, few published evaluations have quantified TIER.Net data quality relative to national sources. We aimed to evaluate how well decentralised ART referral and laboratory result data are captured in TIER.Net. We conducted a retrospective analysis comparing TIER.Net to national electronic health systems. For decentralised ART, we used de-identified data from 56 clinics in eThekwini (2020-2023) and compared the annual number of TIER.Net decentralised ART referrals to ART prescriptions in the Synchronised National Communication in Health (SyNCH) database. For laboratory data, we used de-identified records from 103 clinics in KwaZulu-Natal (2015-2022) and compared the annual number of TIER.Net viral load (VL) and CD4 tests with the number in National Health Laboratory Service (NHLS). The proportion of SyNCH decentralised ART prescriptions and NHLS VL and CD4 counts captured in TIER.Net were calculated by clinic, and trends were assessed using linear mixed-effects models (LMMs). The median proportion of SyNCH decentralised ART prescriptions captured in TIER.Net was 104.4% (IQR: 99.85-115.1 % ) in 2020 and 102.44% (IQR: 100.5-104.5%) in 2023. The LMM estimated an annual decrease of 2.8% (95% CI: -4.8; -0.9%). The median proportion of NHLS VLs captured in TIER.Net was 85.7% (IQR: 70.0-97.9%) in 2015 and 99.1% (IQR: 94.5-102.5%) in 2022. The LMM estimated an annual increase of 1.8% (95% CI: 1.4-2.1%). The median proportion of NHLS CD4s captured in TIER.Net was 74.3% (IQR: 63.9-85.4%) in 2015 and 80.1% (IQR: 68.4-89.1%) in 2022. The LMM estimated no statistically significant trend over time (-0.08%, 95% CI: -0.6; 0.4%). Reassuringly, capture of TIER.Net for decentralised ART and VL data has improved to near 100%, but CD4 count capture remains sub-optimal, highlighting strengths and limitations of conducting analyses with this critical HIV programme database.