Cervical precancer and cancer incidence among insured women with and without HIV in South Africa.

HIV infection increases the risk of developing cervical cancer; however, longitudinal studies in sub-Saharan Africa comparing cervical cancer rates between women living with HIV (WLWH) and women without HIV are scarce. To address this gap, we compared cervical precancer and cancer incidence rates between WLWH and women without HIV in South Africa using reimbursement claims data from a medical insurance scheme from January 2011 to June 2020. We used Royston-Parmar flexible parametric survival models to estimate cervical precancer and cancer incidence rates as a continuous function of age, stratified by HIV status. Our study population consisted of 518 048 women, with exclusions based on the endpoint of interest. To analyse cervical cancer incidence, we included 517 312 women, of whom 564 developed cervical cancer. WLWH had an ~3-fold higher risk of developing cervical precancer and cancer than women without HIV (adjusted hazard ratio for cervical cancer: 2.99; 95% confidence interval [CI]: 2.40-3.73). For all endpoints of interest, the estimated incidence rates were higher in WLWH than women without HIV. Cervical cancer rates among WLWH increased at early ages and peaked at 49 years (122/100 000 person-years; 95% CI: 100-147), whereas, in women without HIV, incidence rates peaked at 56 years (40/100 000 person-years; 95% CI: 36-45). Cervical precancer rates peaked in women in their 30s. Analyses of age-specific cervical cancer rates by HIV status are essential to inform the design of targeted cervical cancer prevention policies in Southern Africa and other regions with a double burden of HIV and cervical cancer.

Same-Day Antiretroviral Therapy Initiation as a Predictor of Loss to Follow-up and Viral Suppression Among People With Human Immunodeficiency Virus in Sub-Saharan Africa.

BACKGROUND: Treat-All guidelines recommend initiation of antiretroviral therapy (ART) for all people with HIV (PWH) on the day of diagnosis when possible, yet uncertainty exists about the impact of same-day ART initiation on subsequent care engagement. We examined the association of same-day ART initiation with loss to follow-up and viral suppression among patients in 11 sub-Saharan African countries. METHODS: We included ART-naive adult PWH from sites participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium who enrolled in care after Treat-All implementation and prior to January 2019. We used multivariable Cox regression to estimate the association between same-day ART initiation and loss to follow-up and Poisson regression to estimate the association between same-day ART initiation and 6-month viral suppression. RESULTS: Among 29 017 patients from 63 sites, 18 584 (64.0%) initiated ART on the day of enrollment. Same-day ART initiation was less likely among those with advanced HIV disease versus early-stage disease. Loss to follow-up was significantly lower among those initiating ART ≥1 day of enrollment, compared with same-day ART initiators (20.6% vs 27.7%; adjusted hazard ratio: .66; 95% CI .57-.76). No difference in viral suppression was observed by time to ART initiation (adjusted rate ratio: 1.00; 95% CI: .98-1.02). CONCLUSIONS: Patients initiating ART on the day of enrollment were more frequently lost to follow-up than those initiating later but were equally likely to be virally suppressed. Our findings support recent World Health Organization recommendations for providing tailored counseling and support to patients who accept an offer of same-day ART.

Mental Health, ART Adherence, and Viral Suppression Among Adolescents and Adults Living with HIV in South Africa: A Cohort Study.

We followed adolescents and adults living with HIV aged older than 15 years who enrolled in a South African private-sector HIV programme to examine adherence and viral non-suppression (viral load > 400 copies/mL) of participants with (20,743, 38%) and without (33,635, 62%) mental health diagnoses. Mental health diagnoses were associated with unfavourable adherence patterns. The risk of viral non-suppression was higher among patients with organic mental disorders [adjusted risk ratio (aRR) 1.55, 95% confidence interval (CI) 1.22-1.96], substance use disorders (aRR 1.53, 95% CI 1.19-1.97), serious mental disorders (aRR 1.30, 95% CI 1.09-1.54), and depression (aRR 1.19, 95% CI 1.10-1.28) when compared with patients without mental health diagnoses. The risk of viral non-suppression was also higher among males, adolescents (15-19 years), and young adults (20-24 years). Our study highlights the need for psychosocial interventions to improve HIV treatment outcomes-particularly of adolescents and young adults-and supports strengthening mental health services in HIV treatment programmes.

RESUMEN: Monitoreamos adolescentes y adultos mayores de 15 años que viven con VIH y que están registrados en un programa privado Surafricano para el tratamiento del VIH. Nuestro propósito fue examinar adherencia a los medicamentos y supresión viral (carga viral < 400 copias/mL) en los participantes con (20,743, 38%) y sin (33,635, 62%) diagnósticos de salud mental. Los diagnósticos de salud mental estuvieron asociados con patrones de adherencia desfavorables. Comparados con pacientes sin diagnósticos de salud mental, el riesgo de no supresión viral fue más alto entre pacientes con desórdenes mentales orgánicos [riesgo relativo ajustado (aRR) 1.55, 95% intervalo de confidencia (CI) 1.22­1.96], desórdenes en el uso de sustancias (aRR 1.53, 95% CI 1.19­1.97), desórdenes mentales serios (aRR 1.30, 95% CI 1.09­1.54), y depresión (aRR 1.19, 95% CI 1.10­1.28). El riesgo de no supresión viral también fue más alto en hombres que en mujeres, en adolescentes (15­19 años), y en adultos jóvenes. Nuestro estudio resalta la necesidad de intervenciones psicosociales para mejorar los resultados del tratamiento contra el VIH ­particularmente en adolescentes y adultos jóvenes­, y respalda el fortalecimiento de servicios de salud mental como parte de los programas para el tratamiento del VIH.

The Impact of the COVID-19 Pandemic and Associated Control Measures on the Mental Health of the General Population : A Systematic Review and Dose-Response Meta-analysis.

BACKGROUND: To what extent the COVID-19 pandemic and its containment measures influenced mental health in the general population is still unclear. PURPOSE: To assess the trajectory of mental health symptoms during the first year of the pandemic and examine dose-response relations with characteristics of the pandemic and its containment. DATA SOURCES: Relevant articles were identified from the living evidence database of the COVID-19 Open Access Project, which indexes COVID-19-related publications from MEDLINE via PubMed, Embase via Ovid, and PsycInfo. Preprint publications were not considered. STUDY SELECTION: Longitudinal studies that reported data on the general population's mental health using validated scales and that were published before 31 March 2021 were eligible. DATA EXTRACTION: An international crowd of 109 trained reviewers screened references and extracted study characteristics, participant characteristics, and symptom scores at each timepoint. Data were also included for the following country-specific variables: days since the first case of SARS-CoV-2 infection, the stringency of governmental containment measures, and the cumulative numbers of cases and deaths. DATA SYNTHESIS: In a total of 43 studies (331 628 participants), changes in symptoms of psychological distress, sleep disturbances, and mental well-being varied substantially across studies. On average, depression and anxiety symptoms worsened in the first 2 months of the pandemic (standardized mean difference at 60 days, -0.39 [95% credible interval, -0.76 to -0.03]); thereafter, the trajectories were heterogeneous. There was a linear association of worsening depression and anxiety with increasing numbers of reported cases of SARS-CoV-2 infection and increasing stringency in governmental measures. Gender, age, country, deprivation, inequalities, risk of bias, and study design did not modify these associations. LIMITATIONS: The certainty of the evidence was low because of the high risk of bias in included studies and the large amount of heterogeneity. Stringency measures and surges in cases were strongly correlated and changed over time. The observed associations should not be interpreted as causal relationships. CONCLUSION: Although an initial increase in average symptoms of depression and anxiety and an association between higher numbers of reported cases and more stringent measures were found, changes in mental health symptoms varied substantially across studies after the first 2 months of the pandemic. This suggests that different populations responded differently to the psychological stress generated by the pandemic and its containment measures. PRIMARY FUNDING SOURCE: Swiss National Science Foundation. (PROSPERO: CRD42020180049).

Outcomes of Patients Lost to Follow-up in African Antiretroviral Therapy Programs: Individual Patient Data Meta-analysis.

Background: Low retention on combination antiretroviral therapy (cART) has emerged as a threat to the Joint United Nations Programme on human immunodeficiency virus (HIV)/AIDS (UNAIDS) 90-90-90 targets. We examined outcomes of patients who started cART but were subsequently lost to follow-up (LTFU) in African treatment programs. Methods: This was a systematic review and individual patient data meta-analysis of studies that traced patients who were LTFU. Outcomes were analyzed using cumulative incidence functions and proportional hazards models for the competing risks of (i) death, (ii) alive but stopped cART, (iii) silent transfer to other clinics, and (iv) retention on cART. Results: Nine studies contributed data on 7377 patients who started cART and were subsequently LTFU in sub-Saharan Africa. The median CD4 count at the start of cART was 129 cells/µL. At 4 years after the last clinic visit, 21.8% (95% confidence interval [CI], 20.8%-22.7%) were known to have died, 22.6% (95% CI, 21.6%-23.6%) were alive but had stopped cART, 14.8% (95% CI, 14.0%-15.6%) had transferred to another clinic, 9.2% (95% CI, 8.5%-9.8%) were retained on cART, and 31.6% (95% CI, 30.6%-32.7%) could not been found. Mortality was associated with male sex, more advanced disease, and shorter cART duration; stopping cART with less advanced disease andlonger cART duration; and silent transfer with female sex and less advanced disease. Conclusions: Mortality in patients LTFU must be considered for unbiased assessments of program outcomes and UNAIDS targets in sub-Saharan Africa. Immediate start of cART and early tracing of patients LTFU should be priorities.

Patterns of caesarean section in HIV infected and non-infected women in Malawi: is caesarean section used for PMTCT?

BACKGROUND: Caesarean section (CS) is not recommended for PMTCT in Malawi HIV Guidelines, contrary to most high-income countries where CS is indicated if viral suppression is sub-optimal pre-delivery. We describe patterns of CS in HIV-infected and uninfected women in Malawi and explored if insight into the use of Elective CS (ECS) for PMTCT could be obtained. METHODS: We used routinely collected data from individual medical records from 17 large health facilities in the central and southern regions of Malawi, from January 2010 to December 2013. We included data from maternity registers from all HIV-positive women, and randomly selected around every fourth woman with negative or unknown HIV status. We used multivariable logistic regressions and cluster-based robust standard errors to examine independent associations of patient- and facility characteristics with CS and ECS. RESULTS: We included 62,033 women in the analysis. The weighted percentage of women who had a spontaneous vaginal delivery was 80.0% (CI 95% 79.5-80.4%); 2.4% (95% CI 2.3-2.6%) had a vacuum extraction; 2.3% (95% CI 2.2-2.5%) had a vaginal breech delivery; 14.0% (95% CI 13.6-14.4%) had a CS while for 1.3% (95% CI 1.2-1.4%) the mode of delivery was not recorded. Prevalence of CS without recorded medical or obstetric indication (ECS) was 5.1%, (n = 3152). Presence of maternal and infant complications and older age were independently associated with CS delivery. HIV-positive women were less likely to have ECS than HIV negative women (aOR 0.65; 95%-CI 0.57-0.74). Among HIV-positive women, those on antiretrovirals (ARV's) for ≥4 weeks prior to delivery were less likely to have ECS than HIV-positive women who had not received ARVs during pregnancy (aOR 0.81; 95% CI 0.68-0.96). CONCLUSIONS: The pattern of CS's in Malawi is largely determined by maternal and infant complications. Positive HIV status was negatively associated with CS delivery, possibly because health care workers were concerned about the risk of occupational HIV transmission and the known increased risk of post-operative complications. Our results leave open the possibility that CS is practiced to prevent MTCT given that ECS was more common among women at high risk of MTCT due to no or short exposure to ARV's.

Adherence to Antiretroviral Therapy During and After Pregnancy: Cohort Study on Women Receiving Care in Malawi's Option B+ Program.

BACKGROUND: Adherence to antiretroviral therapy (ART) is crucial to preventing mother-to-child transmission of human immunodeficiency virus (HIV) and ensuring the long-term effectiveness of ART, yet data are sparse from African routine care programs on maternal adherence to triple ART. METHODS: We analyzed data from women who started ART at 13 large health facilities in Malawi between September 2011 and October 2013. We defined adherence as the percentage of days "covered" by pharmacy claims. Adherence of ≥90% was deemed adequate. We calculated inverse probability of censoring weights to adjust adherence estimates for informative censoring. We used descriptive statistics, survival analysis, and pooled logistic regression to compare adherence between pregnant and breastfeeding women eligible for ART under Option B+, and nonpregnant and nonbreastfeeding women who started ART with low CD4 cell counts or World Health Organization clinical stage 3/4 disease. RESULTS: Adherence was adequate for 73% of the women during pregnancy, for 66% in the first 3 months post partum, and for about 75% during months 4-21 post partum. About 70% of women who started ART during pregnancy and breastfeeding adhered adequately during the first 2 years of ART, but only about 30% of them had maintained adequate adherence at every visit. Risk factors for inadequate adherence included starting ART with an Option B+ indication, at a younger age, or at a district hospital or health center. CONCLUSIONS: One-third of women retained in the Option B+ program adhered inadequately during pregnancy and breastfeeding, especially soon after delivery. Effective interventions to improve adherence among women in this program should be implemented.

Prostate Cancer Diagnosis Rates among Insured Men with and without HIV in South Africa: A Cohort Study.

BACKGROUND: Several studies have found lower prostate cancer diagnosis rates among men with human immunodeficiency virus (HIV; MWH) than men without HIV but reasons for this finding remain unclear. METHODS: We used claims data from a South African private medical insurance scheme (July 2017- July 2020) to assess prostate cancer diagnosis rates among men aged ≥ 18 years with and without HIV. Using flexible parametric survival models, we estimated hazard ratios (HR) for the association between HIV and incident prostate cancer diagnoses. We accounted for potential confounding by age, population group, and sexually transmitted infections (confounder-adjusted model) and additionally for potential mediation by prostatitis diagnoses, prostate-specific antigen testing, and prostate biopsies (fully adjusted model). RESULTS: We included 288,194 men, of whom 20,074 (7%) were living with HIV. Prostate cancer was diagnosed in 1,614 men without HIV (median age at diagnosis: 67 years) and in 82 MWH (median age at diagnosis: 60 years). In the unadjusted analysis, prostate cancer diagnosis rates were 35% lower among MWH than men without HIV [HR, 0.65; 95% confidence interval (CI), 0.52-0.82]. However, this association was no longer evident in the confounder-adjusted model (HR, 1.03; 95% CI, 0.82-1.30) or in the fully adjusted model (HR, 1.14; 95% CI, 0.91-1.44). CONCLUSIONS: When accounting for potential confounders and mediators, our analysis found no evidence of lower prostate cancer diagnosis rates among MWH than men without HIV in South Africa. IMPACT: Our results do not support the hypothesis that HIV decreases the risk of prostate cancer.

Courier delivery of antiretroviral therapy: a cohort study of a South African private-sector HIV programme.

INTRODUCTION: Courier delivery has become a popular antiretroviral therapy (ART) distribution method in some HIV care settings, yet data on ART courier delivery and how it relates to ART outcomes are scarce. We studied the differences in viral suppression rates between individuals from a South African private sector HIV programme receiving ART by courier delivery and those receiving ART through traditional retail dispensing. METHODS: Individuals aged 15 years or older who were actively enrolled in the Aid for AIDS programme between January 2011 and July 2022 were eligible for the analysis. The outcome of interest was viral suppression defined as a viral load (VL) <400 copies per ml. We calculated adjusted odds ratios (OR) for the association between the ART distribution method and viral suppression, comparing those receiving refills through courier pharmacies versus retail dispensing at the time of the VL testing. We used generalized estimating equations to account for repeated VL testing of the same individual. The models were adjusted for age, sex, calendar year, ART regimen, history of mental illness and medical insurance scheme. We computed adjusted ORs for the calendar periods 2011-2013, 2014-2016, 2017-2019, 2020-2022 and overall. RESULTS: We extracted 442,619 VL measurements from 68,720 eligible individuals, 39,406 (57.3%) were women. The median number of VL measurements per individual was 6 (IQR 3-10). VL suppression was detected in 398,901 (90.1%) tests, and 185,701 (42.0%) of the tests were taken while the individual was receiving ART by courier delivery. Overall, courier delivery was associated with 5% higher odds of viral suppression than retail dispensing (adjusted OR 1.05, 95% CI 1.02-1.08). The strength and direction of this association varied by calendar period, with an adjusted OR of 1.37 (95% CI 1.27-1.48) in 2011-2013 and 1.02 (95% CI 0.97-1.07) in 2020-2022. CONCLUSIONS: Courier delivery of ART is a viable alternative to retail dispensing in the South African private sector, as it was associated with higher viral suppression until 2016 and similar suppression rates in recent years. Further research is needed to investigate the potential benefits and drawbacks of courier delivery of ART in both private and public healthcare settings.

Post-traumatic stress disorder as a risk factor for major adverse cardiovascular events: a cohort study of a South African medical insurance scheme.

AIMS: Prior research, largely focused on US male veterans, indicates an increased risk of cardiovascular disease among individuals with post-traumatic stress disorder (PTSD). Data from other settings and populations are scarce. The objective of this study is to examine PTSD as a risk factor for incident major adverse cardiovascular events (MACEs) in South Africa. METHODS: We analysed reimbursement claims (2011-2020) of a cohort of South African medical insurance scheme beneficiaries aged 18 years or older. We calculated adjusted hazard ratios (aHRs) for associations between PTSD and MACEs using Cox proportional hazard models and calculated the effect of PTSD on MACEs using longitudinal targeted maximum likelihood estimation. RESULTS: We followed 1,009,113 beneficiaries over a median of 3.0 years (IQR 1.1-6.0). During follow-up, 12,662 (1.3%) persons were diagnosed with PTSD and 39,255 (3.9%) had a MACE. After adjustment for sex, HIV status, age, population group, substance use disorders, psychotic disorders, major depressive disorder, sleep disorders and the use of antipsychotic medication, PTSD was associated with a 16% increase in the risk of MACEs (aHR 1.16, 95% confidence interval (CI) 1.05-1.28). The risk ratio for the effect of PTSD on MACEs decreased from 1.59 (95% CI 1.49-1.68) after 1 year of follow-up to 1.14 (95% CI 1.11-1.16) after 8 years of follow-up. CONCLUSION: Our study provides empirical support for an increased risk of MACEs in males and females with PTSD from a general population sample in South Africa. These findings highlight the importance of monitoring cardiovascular risk among individuals diagnosed with PTSD.

Changes in the prevalence of mental health problems during the first year of the pandemic: a systematic review and dose-response meta-analysis.

AIM: To describe the pattern of the prevalence of mental health problems during the first year of the COVID-19 pandemic and examine the impact of containment measures on these trends. METHODS: We identified articles published until 30 August 2021 that reported the prevalence of mental health problems in the general population at two or more time points. A crowd of 114 reviewers extracted data on prevalence, study and participant characteristics. We collected information on the number of days since the first SARS-CoV-2 infection in the study country, the stringency of containment measures and the number of cases and deaths. We synthesised changes in prevalence during the pandemic using a random-effects model. We used dose-response meta-analysis to evaluate the trajectory of the changes in mental health problems. RESULTS: We included 41 studies for 7 mental health conditions. The average odds of symptoms increased during the pandemic (mean OR ranging from 1.23 to 2.08). Heterogeneity was very large and could not be explained by differences in participants or study characteristics. Average odds of psychological distress, depression and anxiety increased during the first 2 months of the pandemic, with increased stringency of the measures, reported infections and deaths. The confidence in the evidence was low to very low. CONCLUSIONS: We observed an initial increase in the average risk of psychological distress, depression-related and anxiety-related problems during the first 2 months of the pandemic. However, large heterogeneity suggests that different populations had different responses to the challenges imposed by the pandemic.

Effect of the Friendship Bench Intervention on Antiretroviral Therapy Outcomes and Mental Health Symptoms in Rural Zimbabwe: A Cluster Randomized Trial.

Importance: Common mental disorders (CMD), which include depression and anxiety, are prevalent among people living with HIV and are associated with suboptimal antiretroviral therapy (ART) adherence. Objective: To assess the effect of a lay health worker-led psychological intervention on ART adherence, virologic suppression, and mental health symptoms. Design, Setting, and Participants: Open-label pragmatic cluster trial with 1:1 block randomization of 16 health facilities in rural Bikita, Zimbabwe. Recruitment occurred from October 2018 to December 2019, and participants were followed up for 12 months, ending in December 2020. Participants were adults aged 18 years and older, who spoke English or Shona, screened positive for CMD (Shona Symptoms Questionnaire [SSQ]-14 score ≥9), received first-line ART for 6 or more months, had no World Health Organization stage 4 disease, no psychosis, were not pregnant, and provided informed consent. Data were analyzed from March 2021 to February 2022. Intervention: The Friendship Bench, consisting of 6 lay health worker-led weekly problem-solving therapy sessions and optional peer-led group support. Main Outcomes and Measures: The primary outcome was mean adherence during 2 to 6 months of follow-up, and the secondary outcomes were mean adherence during 1 to 12 months of follow-up, change in SSQ-14 and Patient Health Questionnaire (PHQ-9) scores (3, 6, 9, and 12 months), and viral load suppression (6 and 12 months). Results: A total of 516 participants were recruited (244 in Friendship Bench and 272 in enhanced standard care facilities); 438 (84.9%) were female and the mean (SD) age was 45.6 (10.9) years. Mean (SD) adherence between 2 to 6 months was 89.9% (18.4%) in the Friendship Bench group and 87.2% (20.1%) in the control group. The intervention had no statistically significant effect on adherence between 2 to 6 months (unadjusted mean difference, 1.93 percentage points; 95% CI, -1.20 to 5.06 percentage points; P = .23), between months 1 to 12 (mean difference 0.79 percentage points; 95% CI, -2.14 to 3.71 percentage points; P = .60), or viral suppression. Declines in SSQ-14 scores from baseline to 3 months (difference, -1.65; 95% CI, -3.07 to -0.24), 6 months (difference, -1.57; 95% CI, -2.98 to -0.15), and 9 months (difference, -1.63; 95% CI, -3.05 to -0.22) were greater in the Friendship Bench than the standard care group (P < .05). There were no differences in the decline in the SSQ-14 scores from baseline to 12 months and in declines in PHQ-9 scores from baseline to 3, 6, 9, and 12 months. Conclusions and Relevance: In this randomized trial of HIV-positive participants with CMD, the Friendship Bench intervention had no effect on adherence and viral suppression, possibly due to the absence of skill-based adherence training and a ceiling effect. Trial Registration: ClinicalTrials.gov Identifier: NCT03704805.

Life years lost associated with mental illness: A cohort study of beneficiaries of a South African medical insurance scheme.

BACKGROUND: People with mental illness have a reduced life expectancy, but the extent of the mortality gap and the contribution of natural and unnatural causes to excess mortality among people with mental illness in South Africa are unknown. METHODS: We analysed reimbursement claims from South African medical insurance scheme beneficiaries aged 15-85 years. We estimated excess life years lost (LYL) associated with organic, substance use, psychotic, mood, anxiety, eating, personality, developmental or any mental disorders. RESULTS: We followed 1,070,183 beneficiaries for a median of three years, of whom 282,926 (26.4 %) received mental health diagnoses. Men with a mental health diagnosis lost 3.83 life years (95 % CI 3.58-4.10) compared to men without. Women with a mental health diagnosis lost 2.19 life years (1.97-2.41) compared to women without. Excess mortality varied by sex and diagnosis, from 11.50 LYL (95 % CI 9.79-13.07) among men with alcohol use disorder to 0.87 LYL (0.40-1.43) among women with generalised anxiety disorder. Most LYL were attributable to natural causes (men: 3.42, women: 1.94). A considerable number of LYL were attributable to unnatural causes among men with bipolar (1.52) or substance use (2.45) disorder. LIMITATIONS: Mental diagnoses are based on reimbursement claims. CONCLUSIONS: Premature mortality among South African individuals with mental disorders is high. Our findings support interventions for the prevention, early detection, and treatment of physical comorbidities in this population. Targeted programs for suicide prevention and substance use treatment, particularly among men, can help reduce excess mortality from unnatural causes.

Effect of the Friendship Bench intervention on antiretroviral therapy outcomes and mental health symptoms in rural Zimbabwe: A cluster randomized trial.

Importance: Common mental disorders (CMD) are prevalent in people living with HIV and associated with suboptimal antiretroviral therapy (ART) adherence. Objective: To assess the effect of a lay health worker-led psychological intervention on adherence to ART, virologic suppression and mental health symptoms. Design: Pragmatic cluster trial with block randomization of health facilities. Treatment assignment was known to participants, providers, evaluators, and data analysts. Recruitment started in October 2018 and the last follow-up visit was done in December 2020. Participants were followed up for 12 months. Setting: Sixteen public health care facilities in Bikita, a rural district in Masvingo Province, about 300 km south of Harare. Participants: Men and non-pregnant women aged 18 years or older who spoke English or Shona, screened positive for CMD (Shona Symptoms Questionnaire [SSQ]-14 score ≥9), had received first-line ART for at least six months, had no WHO clinical stage 4 disease, no psychotic symptoms, and gave informed consent. Intervention: The Friendship Bench, a lay health worker-led intervention consisting of six weekly individual counselling sessions of problem-solving therapy and optional peer-led group support. Main Outcomes and Measures: The primary outcome was Medication Event Monitoring System (MEMS) mean adherence between 2-6 months of follow-up. Secondary outcomes included mean adherence between 1-12 months, change from baseline SSQ-14 and Patient Health Questionnaire (PHQ-9) score at 3, 6, 9, and 12 months and change in viral load suppression (viral load <1000 copies per mL) at months 6 and 12. Results: We recruited 516 participants, 244 in Friendship bench and 272 in standard care facilities. The mean age was 45.6 years (SD 10.9), and most participants were women (84.9%). In the Friendship Bench group, 88.1% of participants attended all six individual counselling sessions. Rates of adherence (>85%) and virologic suppression (>90%) were high in both groups. The intervention had no statistically significant effect on adherence or viral suppression. Declines in SSQ-14 scores from baseline to 3 months (-1.65, 95% CI -3.07 to -0.24), 6 months (-1.57, 95% CI -2.98 to -0.15), and 9 months (-1.63, 95% CI -3.05 to -0.22) were greater in the Friendship Bench than the standard care group (p<0.05). There were no differences in the decline in the SSQ-14 scores from baseline to 12 months and in declines in PHQ-9 scores from baseline to 3, 6, 9, and 12 months. Conclusions and Relevance: The Friendship Bench intervention is a feasible and acceptable approach to closing the treatment gap in mental health care in rural Zimbabwe. The intervention improved CMD symptoms but the intervention effect was smaller than previously shown in an urban setting. The intervention had no effect on adherence and viral suppression, possibly due to the absence of skill-based adherence training and ceiling effect. Trial registration: ClinicalTrials.gov Identifier: NCT03704805. Key points: Question: Does the Friendship Bench intervention improve antiretroviral therapy (ART) adherence, viral suppression and mental health symptoms in people living with HIV in rural Zimbabwe?Findings: In this cluster-randomized trial, participants in the intervention group had a significantly greater decrease in symptoms of common mental disorders than those in the control group, but the intervention showed no significant effect on antiretroviral therapy (ART) adherence or viral suppression.Meaning: The intervention did not affect adherence and viral suppression and the effect of the intervention on mental health symptoms was smaller than previously shown.

Life-years lost associated with mental illness: a cohort study of beneficiaries of a South African medical insurance scheme.

Importance: People with mental illness have a reduced life expectancy, but the extent of the mortality gap and the contribution of natural and unnatural causes to excess mortality among people with mental illness in South Africa are unknown. Objective: To quantify excess mortality due to natural and unnatural causes associated with mental illness. Design setting and participants: Cohort study using reimbursement claims and vital registration of beneficiaries of a South African medical insurance scheme, aged 15-84 years and covered by medical insurance at any point between January 1, 2011, and June 30, 2020. Exposures: ICD-10 diagnoses of mental disorders including organic, substance use, psychotic, mood, anxiety, eating, personality, and developmental disorders. Outcomes: Mortality from natural, unnatural, unknown and all causes, as measured by the life-years lost (LYL) metric. Results: We followed 1 070 183 beneficiaries (51.7% female, median age 36.1 years for a median duration of 3.0 years, of whom 282 926 (26.4%) received mental health diagnoses and 27 640 (2.6%) died. Life expectancy of people with mental health diagnoses was 3.83 years (95% CI 3.58-4.10) shorter for men and 2.19 years (1.97-2.41) shorter for women. Excess mortality varied by sex and diagnosis, ranging from 11.50 LYL (95% CI 9.79-13.07) among men with alcohol use disorder to 0.87 LYL (0.40-1.43) among women with generalised anxiety disorder. Most LYL were attributable to natural causes (3.42 among men and 1.94 among women). A considerable number of LYL were attributable to unnatural causes among men with bipolar (1.52) or substance use (2.45) disorder. Conclusions and Relevance: The burden of premature mortality among persons with mental disorders in South Africa is high. Our findings support implementing interventions for prevention, early detection, and treatment of physical comorbidities among people with mental disorders. Suicide prevention and substance use treatment programmes are needed to reduce excess mortality from unnatural causes, especially among men. Key points: Question: How much shorter is the life expectancy of people with mental illness compared to the general population and how many life years are lost due to natural and unnatural causes of death?Findings: The life expectancy of people with mental health diagnoses was 3.83 years shorter for men and 2.19 years shorter for women. Most excess life years lost were attributable to natural causes (3.42 among men and 1.94 among women). However, bipolar and substance use disorders were associated with considerable premature mortality from unnatural causes.Meaning: Our findings support the implementation of interventions for improving the physical health of people with mental illness and targeted suicide prevention and substance use treatment programmes.

Authorship inequalities in global health research: the IeDEA Southern Africa collaboration.

BACKGROUND: The International epidemiology Databases to Evaluate AIDS conducts research in several regions, including in Southern Africa. We assessed authorship inequalities for the Southern African region, which is led by South African and Swiss investigators. METHODS: We analysed authorships of publications from 2007 to 2020 by gender, country income group, time and citation impact. We used 2020 World Bank categories to define income groups and the relative citation ratio (RCR) to assess citation impact. Authorship parasitism was defined as articles without authors from the countries where the study was conducted. A regression model examined the probability of different authorship positions. RESULTS: We included 313 articles. Of the 1064 contributing authors, 547 (51.4%) were women, and 223 (21.0%) were from 32 low-income/lower middle-income countries (LLMICs), 269 (25.3%) were from 13 upper middle-income countries and 572 (53.8%) were from 25 high-income countries (HICs). Most articles (150/157, 95.5%) reporting data from Southern Africa included authors from all participating countries. Women were more likely to be the first author than men (OR 1.74; 95% CI 1.06 to 2.83) but less likely to be last authors (OR 0.63; 95% CI 0.40 to 0.99). Compared with HIC, LLMIC authors were less likely to publish as first (OR 0.21; 95% CI 0.11 to 0.41) or last author (OR 0.20; 95% CI 0.09 to 0.42). The proportion of women and LLMIC first and last authors increased over time. The RCR tended to be higher, indicating greater impact, if first or last authors were from HIC (p=0.06). CONCLUSIONS: This analysis of a global health collaboration co-led by South African and Swiss investigators showed little evidence of authorship parasitism. There were stark inequalities in authorship position, with women occupying more first and men more last author positions and researchers from LLMIC being 'stuck in the middle' on the byline. Global health research collaborations should monitor, analyse and address authorship inequalities.

Availability of screening and treatment for common mental disorders in HIV clinic settings: data from the global International epidemiology Databases to Evaluate AIDS (IeDEA) Consortium, 2016-2017 and 2020.

INTRODUCTION: Common mental disorders (CMDs) are highly prevalent among people with HIV. Integrating mental healthcare into HIV care may improve mental health and HIV treatment outcomes. We describe the reported availability of screening and treatment for depression, anxiety and post-traumatic stress disorder (PTSD) at global HIV treatment centres participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) Consortium in 2020 and changes in availability at sites in low- or middle-income countries (LMICs) between 2016/2017 and 2020. METHODS: In 2020, 238 sites contributing individual-level data to the IeDEA Consortium and in 2016/2017 a stratified random sample of IeDEA sites in LMICs were eligible to participate in site surveys on the availability of screening and treatment for CMDs. We assessed trends over time for 68 sites across 27 LMICs that participated in both surveys. RESULTS: Among the 238 sites eligible to participate in the 2020 site survey, 227 (95%) participated, and mental health screening and treatment data were available for 223 (98%) sites across 41 countries. A total of 95 sites across 29 LMICs completed the 2016/2017 survey. In 2020, 68% of sites were in urban settings, and 77% were in LMICs. Overall, 50%, 14% and 12% of sites reported screening with a validated instrument for depression, anxiety and PTSD, respectively. Screening plus treatment in the form of counselling was available for depression, anxiety and PTSD at 46%, 13% and 11% of sites, respectively. Screening plus treatment in the form of medication was available for depression, anxiety and PTSD at 36%, 11% and 8% of sites, respectively. Among sites that participated in both surveys, screening for depression was more commonly available in 2020 than 2016/2017 (75% vs. 59%, respectively, p = 0.048). CONCLUSIONS: Reported availability of screening for depression increased among this group of IeDEA sites in LMICs between 2016/2017 and 2020. However, substantial gaps persist in the availability of mental healthcare at HIV treatment sites across global settings, particularly in resource-constrained settings. Implementation of sustainable strategies to integrate mental health services into HIV care is needed.

Integrase strand-transfer inhibitor use and cardiovascular events in adults with HIV: an emulation of target trials in the HIV-CAUSAL Collaboration and the Antiretroviral Therapy Cohort Collaboration.

BACKGROUND: A recent observational study suggested that the risk of cardiovascular events could be higher among antiretroviral therapy (ART)-naive individuals with HIV who receive integrase strand-transfer inhibitor (INSTI)-based ART than among those who receive other ART regimens. We aimed to emulate target trials separately in ART-naive and ART-experienced individuals with HIV to examine the effect of using INSTI-based regimens versus other ART regimens on the 4-year risk of cardiovascular events. METHODS: We used routinely recorded clinical data from 12 cohorts that collected information on cardiovascular events, BMI, and blood pressure from two international consortia of cohorts of people with HIV from Europe and North America. For the target trial in individuals who had previously never used ART (ie, ART-naive), eligibility criteria were aged 18 years or older, a detectable HIV-RNA measurement while ART-naive (>50 copies per mL), and no history of a cardiovascular event or cancer. Eligibility criteria for the target trial in those with previous use of non-INSTI-based ART (ie, ART-experienced) were the same except that individuals had to have been on at least one non-INSTI-based ART regimen and be virally suppressed (≤50 copies per mL). We assessed eligibility for both trials for each person-month between January, 2013, and January, 2023, and assigned individuals to the treatment strategy that was compatible with their data. We estimated the standardised 4-year risks of cardiovascular events (myocardial infarction, stroke, or invasive cardiovascular procedure) via pooled logistic regression models adjusting for time and baseline covariates. In per-protocol analyses, we censored individuals if they deviated from their assigned treatment strategy for more than 2 months and weighted uncensored individuals by the inverse of their time-varying probability of remaining uncensored. The denominator of the weight was estimated via a pooled logistic model that included baseline and time-varying covariates. FINDINGS: The analysis in ART-naive individuals included 10 767 INSTI initiators and 8292 non-initiators of INSTI. There were 43 cardiovascular events in INSTI initiators (median follow-up of 29 months; IQR 15-45) and 52 in non-initiators (39 months; 18-47): standardised 4-year risks were 0·76% (95% CI 0·51 to 1·04) in INSTI initiators and 0·75% (0·54 to 0·98) in non-INSTI initiators; risk ratio 1·01 (0·57 to 1·57); risk difference 0·0089% (-0·43 to 0·36). The analysis in ART-experienced individuals included 7875 INSTI initiators and 373 965 non-initiators. There were 56 events in INSTI initiators (median follow-up 18 months; IQR 9-29) and 3103 events (808 unique) in non-INSTI initiators (26 months; 15-37) in non-initiators: standardised 4-year risks 1·41% (95% CI 0·88 to 2·03) in INSTI initiators and 1·48% (1·28 to 1·71) in non-initiators; risk ratio 0·95 (0·60 to 1·36); risk difference -0·068% (-0·60 to 0·52). INTERPRETATION: We estimated that INSTI use did not result in a clinically meaningful increase of cardiovascular events in ART-naive and ART-experienced individuals with HIV. FUNDING: National Institute of Allergy and Infectious Diseases and National Institute on Alcohol Abuse and Alcoholism.

Cancer treatment and survival among cervical cancer patients living with or without HIV in South Africa.

Objective: To compare cancer treatment and all-cause mortality between HIV-positive and HIV-negative cervical cancer patients in South Africa. Methods: We assessed cancer treatment and all-cause mortality in HIV-positive and HIV-negative cervical cancer patients who received cancer treatment within 180 days of diagnosis using reimbursement claims data from a private medical insurance scheme in South Africa between 01/2011 and 07/2020. We assessed treatment provision using logistic regression and factors associated with all-cause mortality using Cox regression. We assigned missing values for histology and ethnicity using multiple imputation. Results: Of 483 included women, 136 (28 %) were HIV-positive at cancer diagnosis (median age: 45.7 years), and 347 (72 %) were HIV-negative (median age: 54.1 years). Among 285 patients with available ICD-O-3 morphology claims codes, the proportion with cervical adenocarcinoma was substantially lower in HIV-positive (4 %) than in HIV-negative patients (26 %). Most HIV-positive patients (67 %) were on antiretroviral therapy at cancer diagnosis. HIV-positive patients were more likely to receive radiotherapy (adjusted odds ratio [aOR] 1.90, 95 % confidence interval [CI] 1.05-3.45) or chemotherapy (aOR 2.02, 95 %CI 0.92-4.43) and less likely to undergo surgery (aOR 0.53, 95 %CI 0.31-0.90) than HIV-negative patients. HIV-positive patients were at a higher risk of death from all causes than HIV-negative patients (adjusted hazard ratio 1.52, 95 %CI 1.06-2.19). Other factors associated with higher all-cause mortality included age > 60 years and metastases at diagnosis. Conclusions: HIV-positive cervical cancer patients in South Africa had higher all-cause mortality than HIV-negative patients which could be explained by differences in tumour progression, clinical care, and HIV-specific mortality.

Virologic non-suppression and early loss to follow up among pregnant and non-pregnant adolescents aged 15-19 years initiating antiretroviral therapy in South Africa: a retrospective cohort study.

INTRODUCTION: Older adolescents aged 15-19 years continue to have high rates of loss to follow up (LTFU), and high rates of virologic non-suppression (VNS) compared to younger adolescents and adults. Adolescent females are at risk of pregnancy, which puts those living with HIV at a dual vulnerability. Our study assessed the factors associated with VNS and LTFU in older adolescents (including pregnant females) who initiated antiretroviral therapy (ART) in South Africa. METHODS: We included adolescents aged 15-19 years initiating ART between 2004 and 2019, with ≥ one viral load (VL) measurement between 4 and 24.5 months, and ≥ 6 months follow-up, from six South African cohorts of the International epidemiology Databases to Evaluate AIDS-Southern Africa (IeDEA-SA). We defined VNS as VL ≥400 copies/ml and LTFU as not being in care for ≥180 days from ART start and not known as transferred out of the clinic or dead in the first 24 months on ART. We examined factors associated with VNS and LTFU using Fine&Gray competing risk models. RESULTS: We included a total of 2733 adolescents, 415 (15.2%) males, median (IQR) age at ART start of 18.6 (17.3, 19.4) years. Among females, 585/2318 (25.2%) were pregnant. Over the 24-month follow-up, 424 (15.5%) of all adolescents experienced VNS: range (11.1% pregnant females and 20.5% males). Over half of all adolescents were LTFU before any other event could occur. The hazard of VNS reduced with increasing age and CD4 count above 200 cells/µl at ART initiation among all adolescents having adjusted for all measured patient characteristics [adjusted sub-distribution hazard ratio (aSHR) 19 vs. 15 years: 0.50 (95% CI: 0.36, 0.68), aSHR: >500 vs. ≤200 cells/µl: 0.22 (95% CI: 0.16, 0.31)]. The effect of CD4 count persisted in pregnant females. Increasing age and CD4 count >200 cells/µl were risk factors for LTFU among all adolescents. CONCLUSIONS: Older adolescents had a high risk of LTFU shortly after ART start and a low risk of VNS, especially those initiating treatment during pregnancy. Interventions addressing adherence and retention should be incorporated into adolescent-friendly services to prevent VNS and LTFU and endeavour to trace lost adolescents as soon as they are identified.