Background:Since the publication of the Southern African HIV Clinicians Society Gender-Affirming Healthcare (GAHC) Guideline in 2021, global evidence on care for transgender and gender-diverse (TGD) youth has expanded. An updated, locally grounded, evidence-informed assessment of health outcomes can support South African stakeholders, particularly as both adolescents and TGD persons are populations of relevance to HIV prevention, sexual health, and integrated healthcare programmes in South Africa. Objectives:To synthesise global empirical evidence (2021-2025) across psychosocial, endocrine, surgical, policy, and non-medical gender-affirming interventions for TGD youth under 18, with attention to South Africa's social, legal, and health-system, and HIV-service delivery context. Method:A rapid review was conducted across 12 databases, supplemented by targeted searches for recent systematic reviews. Eligible sources comprised peer-reviewed empirical studies (N ≥ 5) reporting psychosocial or physical health outcomes of relevant interventions for TGD youth under 18 (or their families), and systematic or grey-literature reviews with reproducible methods. Findings were synthesised narratively by intervention domain. Results:The review included 200 primary studies, 29 academic systematic reviews, and four grey-literature reviews. Affirming psychosocial interventions were associated with reduced distress, anxiety and suicidality, and improved functioning and belonging. Puberty blockers and hormone therapy produced expected physiological outcomes under specialist care, with generally mild adverse events and stable or improved mental health. Restrictive policies were linked to poorer mental health, while protective policies improved outcomes. Most studies were small, observational, and Global North-focused. Conclusion:Evidence supports the safety and effectiveness of GAHC for TGD youth. Strengthening affirming care, timely clinical access, and protective policies in South Africa may improve healthcare engagement and support the delivery of integrated adolescent, sexual health, and HIV-related services for TGD youth.
Background: Tenofovir (TFV) is a key antiretroviral used in HIV pre-exposure prophylaxis (PrEP) and treatment, with efficacy contingent on adherence. Quantifying TFV concentrations in dried blood spots (DBS) as tenofovir diphosphate (TFV-DP) is a robust method for determining long-term adherence. However, standardised TFV-DP adherence thresholds in DBS have not been established. Objectives: To map the existing literature on TFV-DP concentration thresholds in DBS for assessing adherence to TFV-based HIV prevention and treatment, and to identify evidence gaps. Method: We conducted a scoping review in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews guidelines. Eight electronic databases were searched for studies reporting TFV-DP concentrations in DBS in relation to adherence thresholds or clinical outcomes for TFV-based PrEP or antiretroviral therapy (ART). Pharmacokinetic simulation or modelling studies used as reference benchmarks were included. Data were screened and extracted by two independent reviewers. We conducted descriptive analysis, tabulating findings. Results: Twenty-two studies were included. TFV-DP adherence thresholds for PrEP and treatment varied widely, from ≥ 650 fmol/punch to ≥ 1850 fmol/punch, reflecting differences in study design, populations and ART formulations. Reference studies defined adherence threshold as ≥ 700 fmol/punch for four doses/week. PrEP studies reported TFV-DP concentrations of 993–1173 fmol/punch for 4–7 doses/week, indicating that the reference threshold was conservative. In treatment studies, concentrations ≥ 1250 fmol/punch were associated with virological suppression, whereas concentrations 800 fmol/punch were linked to an increased risk of viraemia. Conclusion: This review of TFV-DP in DBS for HIV PrEP and treatment supports purpose- and population-specific thresholds and highlights the need for further threshold validation to optimise PrEP and treatment strategies.
Background: Since 2019 dolutegravir-based antiretroviral therapy (ART) has been introduced for South African children and adolescents living with HIV (CALHIV), including those with persistent viral non-suppression. Current guidelines recommend the reuse of abacavir when switching CALHIV weighing < 30 kg with persistent viral non-suppression to dolutegravir-based ART. Objectives: We aimed to describe the viral suppression rates, clinical outcomes and risk factors for non-suppression in CALHIV switching to dolutegravir-based ART following persistent viral non-suppression. Method: We performed a retrospective cohort study at Tygerberg Hospital in Cape Town, South Africa. Results: We identified 39 children, 18 girls (46.2%). Median age at switch to a dolutegravir-based regimen was 7.2 years. Median duration on treatment pre-switch was 5.6 years. After switching to a dolutegravir-based regimen, 21 children (55.3%) achieved viral suppression. Abacavir was recycled with dolutegravir in 31 children (available viral load for 30/31) of whom 50.0% suppressed. Treatment interruptions were common, with 26 (66.7%) and 15 (38.5%) children experiencing at least one interruption in care before and after switching to a dolutegravir-based regimen, respectively. Conclusion: We provide evidence that recycling abacavir is safe in children with persistent viral non-suppression switching to dolutegravir. Supporting adherence and preventing therapy interruption is key to success.
Screening for early asymptomatic cryptococcal antigenaemia is a crucial step in preventing symptomatic cryptococcal meningitis and reducing mortality among people with advanced HIV disease. However, even when early cryptococcal disease is detected, a significant number of people with advanced HIV disease still develop meningitis and die, suggesting barriers to care following a positive serum cryptococcal antigen result. Ten years after the initiation of a national screening programme in South Africa, we discuss progress and implementation challenges and highlight potential solutions identified through a clinical trial to reduce barriers to care for people with early cryptococcal disease. Analysing systems that care for individuals with early cryptococcal disease and creating interventions to optimise available resources are key steps in reducing HIV-associated cryptococcal disease mortality worldwide.
Dolutegravir is an integrase inhibitor in first-line antiretroviral therapy in South Africa. We describe a patient who developed severe drug-induced liver injury on dolutegravir-containing antiretroviral treatment, in whom liver biopsy demonstrated subacute hepatic necrosis, non-necrotising granulomatous inflammation, and bile duct injury: an uncommon histological pattern in dolutegravir-associated hepatotoxicity.
Background: Retention on antiretroviral treatment (ART) is essential for achieving viral suppression and preventing HIV transmission. However, men living with HIV in sub-Saharan Africa are disproportionately lost to follow-up (LTFU), posing significant public health challenges. Objectives: To explore the perceptions, experiences and barriers to ART adherence among men LTFU on ART treatment at three primary healthcare (PHC) facilities in the Govan Mbeki sub-district, Mpumalanga. Method: Qualitative, descriptive, and explorative contextual research methodologies were used to collect data among 21 LTFU men from three PHC facilities in the Govan Mbeki sub-district. Participants were selected using heterogenous purposive sampling, and the sample size was determined by data saturation. Semi-structured, in-depth interviews were conducted from May 2024 to July 2024. The data were thematically analysed using NVivo 14. Results: The study identified key factors affecting ART adherence among men, including stigma, work-related barriers, long clinic waiting times, and medication side effects. Economic pressures, poor service delivery, and negative attitudes from healthcare staff further contributed to ART default. Suggested improvements include extended service hours, male-friendly environments, and better communication with healthcare providers. Conclusion: This study underscores the complex interplay of barriers driving ART disengagement among men and highlights the need for multi-pronged strategies to improve retention. Addressing these barriers is critical for achieving equitable HIV care outcomes and advancing progress toward the Joint United Nations Programme on HIV/AIDS (UNAIDS) 95-95-95 targets.
Background: South Africa faces overlapping epidemics of HIV and sexually transmitted infections (STIs), particularly among men who have sex with men (MSM). Data on asymptomatic Chlamydia trachomatis and Neisseria gonorrhoeae infections in MSM living with HIV are limited. Objectives: To determine the prevalence and incidence of asymptomatic C. trachomatis and N. gonorrhoeae infections among MSM living with HIV. Method: We conducted a pilot randomised controlled trial of the HIV coping and disclosure management intervention among 88 MSM living with HIV in Buffalo City, South Africa. Sexually transmitted infection screening for C. trachomatis and N. gonorrhoeae was performed at baseline and at a 17-week follow-up using nucleic acid amplification testing of urine and rectal swabs. Univariable logistic regression models were used to examine the relationship between conceptually important individual-level variables and any STI at baseline and week 17 of follow-up. Results: Mean age was 30 years in the intervention arm and 33 years in the control arm. At enrolment, most participants had an undetectable HIV viral load (79.1% intervention vs 80.0% control). Syphilis positivity was higher in the intervention arm (9.3% vs 2.3%). Baseline prevalence of STIs was high, including urethral and rectal C. trachomatis and N. gonorrhoeae infections. At week 17, STI prevalence was similar between arms (27.9% intervention vs 28.9% control). Univariable analyses did not identify any factors associated with STI at follow-up in either group. Conclusion: Asymptomatic STIs are highly prevalent and incident among MSM living with HIV in South Africa. Findings highlight the need to strengthen STI prevention, treatment and care services, and to innovative interventions.
Background:HIV is the most common cause of secondary thrombotic thrombocytopenic purpura (TTP) in South Africa. Objectives:To assess the clinical presentations and outcomes of patients treated for HIV-associated and idiopathic TTP. Method:We conducted a retrospective cohort study of patients consecutively diagnosed with TTP from 2010 to 2020 at Groote Schuur Hospital. Patients were identified by reviewing hospital and Western Cape Blood Services records. Kaplan-Meier curves and log-rank tests were used to evaluate remission rates, both overall and by HIV status and treatment group. Logistic regression models were used to identify predictors of remission and relapse. Results:One hundred and thirty-nine patients were included, 85.6% of whom were HIV positive. There were no significant differences in the TTP pentad features by HIV status. Most patients achieved remission (71.9%) with a median time of eight days. Remission occurred significantly earlier in those treated with fresh frozen plasma only, suggesting less severe disease (median = 8 days [interquartile range 6-10]), compared to those requiring plasma exchange, suggesting more severe disease (median = 12 days [interquartile range 8-22]). The overall mortality in the 10-year period was 38.9%, with 10.8% of the surviving patients relapsing after 6 months. There were no significant differences in remission status, time to remission, mortality or relapse by HIV status. All HIV-positive patients who relapsed had defaulted their antiretroviral therapy (ART). Conclusion:HIV status did not affect patient outcomes in our cohort. ART is important in preventing HIV-associated TTP and relapse.
Background:Intimate partner violence (IPV) and HIV incidence rise substantially during adolescence. While surveys from African countries suggest that adult men living with HIV were more likely to be perpetrators of IPV, less is known about boys living with perinatal HIV (PHIV). Objectives:To measure the prevalence and incidence of IPV perpetration between adolescents who acquired HIV perinatally and their HIV-negative peers. Method:Adolescents 15-19 years old, in a sexual or dating relationship, were followed up for 1 year in Soweto, South Africa. We examined prevalence of IPV perpetration using a baseline survey and incidence using weekly prospective mobile phone surveys. Data were collected on emotional, physical, and sexual IPV. Associations between HIV status and IPV were estimated using logistic regression for lifetime and past-year perpetration, and generalised linear mixed models for past 24-h perpetration. Results:Of 498 participants, 251 were living with PHIV, and 247 were HIV-negative at baseline. Lifetime and past-year IPV perpetration were reported by 52% (PHIV 50%, HIV negative 53%) and 34% (PHIV 31%, HIV negative 37%), respectively. Over 12 000 weekly mobile surveys were submitted during follow-up. Participants reported 134 incidences of physical or sexual IPV out of 5032 occasions where the mobile survey coincided with participants seeing a partner. IPV incidence was estimated as three out of every hundred person-days. There was no significant difference in the incidence of perpetration by HIV status. Conclusion:In 3 out of 100 encounters with a partner, physical or sexual IPV perpetration was reported. Boys living with HIV were equally likely to perpetrate violence as HIV-negative boys. Interventions targeted at boys to reduce IPV behaviour should include all adolescents. In boys living with HIV who have regular contact with healthcare providers, there is an opportunity for an intervention to potentially reduce onward HIV transmission.
Background: Key populations experience disproportionate HIV burdens and structural barriers to care. Objective: To compare healthcare utilisation, HIV knowledge and barriers between key population groups (KPG) and non-key populations living with HIV in eThekwini, South Africa. Methods: We analysed the eThekwini Fast-Track Cities Quality of Care survey, a cross-sectional study across 30 high-HIV-burden facilities (April to July 2023). Adults living with HIV completed anonymous questionnaires; groups were compared using χ2 tests and multivariable logistic regression for partner notification. Results: Of 517 analysed participants, 128 (24.8%) were KPG. KPG participants were younger, more recently diagnosed ( 1 year: 9.4% vs 1.3%) and more often on antiretroviral therapy (ART) for 1–4 years (52.3% vs 33.4%), with similar daily adherence (~83%). KPG were more likely to access care via non-governmental organisations (NGOs; 23.4% vs 5.7%). Controls more often understood undetectable viral load (36.0% vs 21.9%) and that treatment benefits outweigh side effects (65.3% vs 42.9%). KPG more frequently reported undetectable viral load (55.5% vs 29.8%), more frequent screening for co-morbid conditions, and transport-cost barriers (15.6% vs 8.2%). In KPG, NGO care was associated with partner notification (adjusted odds ratio 18.06; 95% confidence interval 4.77–68.41). Conclusion: There are marked differences between KPG and adults with HIV in healthcare utilisation, HIV knowledge and structural barriers.
Background: Kaposi sarcoma (KS) remains the most common HIV-associated malignancy in South Africa and continues to contribute substantially to the national disease burden, despite the widespread availability of antiretroviral therapy (ART) since 2004. Objectives: To describe the clinical characteristics and outcomes of patients referred to a multidisciplinary HIV-associated KS clinic. Method: A retrospective, descriptive cohort study was conducted at a South African tertiary hospital, including patients diagnosed with HIV-associated KS between January 2022 and December 2024. Data were deidentified, pooled, and analysed using descriptive statistics and univariate analysis. Results: A total of 137 patients were included. Most were on ART at the time of KS diagnosis, with a median CD4 count of 122 cells/µL. Advanced disease was common, with 85% of patients presenting with AIDS Clinical Trial Group (ACTG) poor risk tumour stage KS, including 43% with visceral involvement. The 1-year all-cause mortality rate was 38%, with visceral KS and lower CD4 counts on presentation being significantly associated with increased risk of death. HIV viral suppression was associated with improved survival, while duration of ART prior to KS diagnosis did not significantly affect outcomes. Conclusion: These findings highlight the late stage at presentation and poor prognosis of HIV-associated KS in this cohort, underscoring the urgent need for improved retention in HIV care and earlier diagnosis of KS.
Background:Conventional HIV testing approaches continue to fall short of overcoming barriers to HIV testing, especially among key and priority populations at higher risk of acquiring and transmitting HIV. Artificial intelligence (AI) and machine learning present a unique opportunity to strengthen prioritised HIV testing through risk prediction and enhanced diagnostic tools. Objective:This study discussed stakeholders' views on opportunities, challenges, contextual considerations and an implementation roadmap and strategic recommendations for integrating AI and machine learning into HIV testing in South Africa. Method:This qualitative study recruited 15 stakeholders in Gauteng Province, using individual semi-structured face-to-face interviews. Thematic content analysis was performed, and the Consolidated Framework for Implementation Research was used to map the implementation roadmap of the results. Results:Four superordinate themes were identified: perceived benefits, challenges, ethical considerations and implementation strategies. The study discussed the opportunity to leverage AI to enhance HIV testing through HIV risk prediction, self-testing support and advanced, accurate diagnostics. However, technological access, digital divide, resource constraints, privacy concerns, skill gaps and staff resistance, among other barriers, were noted. Conclusion:The implementation design should incorporate the perspectives of all stakeholders involved in HIV testing to address human factors and ethical concerns surrounding AI use.
Background: With antiretroviral therapy (ART), people living with HIV (PLHIV) have near-normal life expectancies. As PLHIV get older, diagnosing and managing cardiovascular diseases (CVDs) becomes important. Data on the prevalence of CVD risk factors in PLHIV in Southern Africa remain limited. Objectives: To determine the prevalence of cardiovascular risk factors among PLHIV receiving ART in Lesotho, Southern Africa. Method: We prospectively enrolled PLHIV who were receiving ART and attending care at five healthcare facilities in Lesotho between 04 June 2024 and 28 October 2024. Demographic information, medical history, blood pressure, blood glucose, lipid profile, and body-mass-index were measured, and lifestyle risk factors data (tobacco use, alcohol intake, physical activity, diet) were collected. The Framingham risk score (FRS) estimated the 10-year CVD risk. Results: Of 343 participants, 66.2% were women, and the median age was 50 years (interquartile range 41–59 years old). The prevalence of elevated blood pressure was 49.3%, diabetes mellitus 9.6%, dyslipidaemia 70.6%, and overweight or obesity 62.7%. Tobacco use was reported by 25.7% and alcohol use by 53.6%, of whom 20.1% were heavy drinkers. Of the 343, 89.8% walked or cycled ≥ 10 min daily to commute, 40.2% reported extra salt intake, and 37.0% ate a balanced meal at most once a week. Based on the FRS, 17.6% had a medium and 12.5% a high 10-year CVD risk. Conclusion: Cardiovascular risk factors are highly prevalent among PLHIV on ART in Lesotho, with nearly one-third at medium or high 10-year CVD risk. These findings support integration of CVD risk management into HIV care in Lesotho.
Background: South Africa has a high prevalence of HIV and substance use, with 13% of the population meeting criteria for lifetime substance use disorder (SUD). Substance disorders are associated with adverse health outcomes, including poor adherence to antiretroviral therapy (ART), reduced health-seeking behaviour and increased risk-taking behaviour. Limited research has explored the perspectives of people with HIV in low- and middle-income countries when accessing substance use treatment. Objectives: To identify barriers and facilitators influencing engagement in substance use treatment programmes among people with HIV and SUDs, drawing on perspectives from both patients and healthcare providers. Method: This qualitative study analysed individual interviews from Project Khanya, a peer-delivered intervention promoting ART adherence among adults living with HIV with at least a moderate SUD. Using criterion sampling, 34 adults with HIV and nine healthcare providers involved in HIV or substance use care were included. Inductive thematic analysis of transcripts from audio recordings identified individual, social, and structural factors influencing treatment engagement. Results: Participants had a mean age of 39.2 years and 48% were female; providers had a mean age of 40.8 years and were predominantly female. Five main subthemes influenced engagement in substance use treatment: social support, substance use, service-related factors, readiness to change, and financial constraints. Facilitators included strong social support, positive healthcare experiences, outreach, psychoeducation, insight, and reduced substance use, while barriers included poor support, stigma, negative healthcare interactions, financial challenges, and ongoing substance use. Conclusion: Intersectional stigma, privacy concerns, and ongoing substance use hinder engagement in HIV and SUD treatment, whereas holistic, person-centred approaches can improve programme attendance and health outcomes.
Background:HIV prevalence among pregnant women in South Africa was very high at 25.3% of infections reported in 2022. KwaZulu-Natal province had the highest HIV prevalence of 34.2%, followed by the Eastern Cape with 32.0% infections, and the Free State with a prevalence of 28.8%. Objectives:To determine the HIV prevalence and healthcare services provided to pregnant women with HIV at primary healthcare clinics in the Free State province. Method:This was a retrospective evaluation of all antenatal records from 2020 to 2023 at primary healthcare facilities in the Free State province, South Africa. All pregnant women who started antenatal care and delivered at the clinic were included in the study. Maternal demographic and clinical data, including HIV status, the clinical management of HIV, and perinatal outcomes were recorded. Maternal records of unbooked mothers and those who did not deliver at the clinic were excluded. Results:The antenatal records of 668 pregnant women during the period 2020-2023 were reviewed. The prevalence of HIV was 27.9%, of which 22.4% tested for the first time at booking. Among pregnant women living with HIV, 4.2% had a CD4-count of < 200 cells/mm3, 48.7% had no viral load recorded and 85% were on antiretroviral therapy. Only 69.6% of the HIV-negative women were retested. All infants (n = 187) born to mothers living with HIV had a negative HIV birth polymerase chain reaction test. Approximately 41% of the HIV-exposed infants had a low-birth weight. In addition, two low-birthweight infants were stillbirths. Conclusion:HIV prevalence among pregnant women remains high, with gaps in viral load monitoring and HIV retesting and early antenatal booking. Low-birth-weight rates were higher among HIV-exposed infants, indicating ongoing vulnerability despite available services.
Background:Targeted Universal Tuberculosis Testing (TUTT) is a strategy for early tuberculosis (TB) detection among people with HIV (PWH); however, drop-offs at key cascade stages limit its effectiveness. Objectives:This study examines determinants of drop-offs at three stages: rapid molecular diagnostic test for TB (Xpert) TB treatment initiation, and completion. Method:We conducted a retrospective analysis of routinely collected data in fiscal year 2022 from PWH on antiretroviral therapy (ART) in rural and urban facilities in KwaZulu-Natal, South Africa. Logistic regression identified determinants of drop-offs. Results:Among 104 859 PWH, 66.7% were not tested using Xpert. Drop-offs were higher among PWH already on ART (Adjusted Odds Ratio [aOR] = 60.65, 95% confidence interval [CI]: 55.11-66.75), and those in multi-month dispensing (MMD; aOR = 1.42, 95% CI: 1.33-1.52) and differentiated models of care (DMoC; aOR = 1.10, 95% CI: 1.03-1.18) versus standard of care. Symptomatic PWH were less likely to experience Xpert drop-offs (aOR = 0.009, 95% CI: 0.008-0.011) than those without symptoms recorded. Of 1746 PWH diagnosed with TB, 6.3% did not initiate treatment, with higher drop-offs in DMoC (aOR = 29.22, 95% CI: 13.29-64.23) and MMD (aOR = 8.65, 95% CI: 2.72-27.48), but lower among symptomatic PWH (aOR = 0.05, 95% CI: 0.03-0.11). Among 1636 who started TB treatment, 25.6% did not complete it. Drop-offs were higher among those with previous TB (aOR = 2.50, 95% CI: 1.71-3.66), and lower among symptomatic PWH (aOR = 0.21, 95% CI: 0.15-0.29). Conclusion:Findings reveal substantial drop-offs in Xpert testing and TB treatment completion, especially among PWH already on ART. Targeted strategies to identify and retain PWH at highest risk of drop-offs are important for optimising TUTT.
