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 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 (07/2017-07/2020) 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 (PSA) 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 men with HIV than men without HIV in South Africa. IMPACT: Our results do not support the hypothesis that HIV decreases the risk of prostate cancer.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Diagnosis and treatment of opioid-related disorders in a South African private sector medical insurance scheme: A cohort study.

BACKGROUND: The use of opioids is increasing globally, but data from low- and middle-income countries on opioid-related mental and behavioural disorders (hereafter referred to as opioid-related disorders) are scarce. This study examines the incidence of opioid-related disorders, opioid agonist use, and excess mortality among persons with opioid-related disorders in South Africa's private healthcare sector. METHODS: We analysed longitudinal data of beneficiaries (≥ 11 years) of a South African medical insurance scheme using reimbursement claims from Jan 1, 2011, to Jul 1, 2020. Beneficiaries were classified as having an opioid-related disorder if they received an opioid agonist (buprenorphine or methadone) or an ICD-10 diagnosis for harmful opioid use (F11.1), opioid dependence or withdrawal (F11.2-4), or an unspecified or other opioid-related disorder (F11.0, F11.5-9). We calculated adjusted hazard ratios (aHR) for factors associated with opioid-related disorders, estimated the cumulative incidence of opioid agonist use after receiving an ICD-10 diagnosis for opioid dependence or withdrawal, and examined excess mortality among beneficiaries with opioid-related disorders. RESULTS: Of 1,251,458 beneficiaries, 1286 (0.1%) had opioid-related disorders. Between 2011 and 2020, the incidence of opioid-related disorders increased by 12% (95% CI 9%-15%) per year. Men, young adults in their twenties, and beneficiaries with co-morbid mental health or other substance use disorders were at increased risk of opioid-related disorders. The cumulative incidence of opioid agonist use among beneficiaries who received an ICD-10 diagnosis for opioid dependence or withdrawal was 18.0% (95% CI 14.0-22.4) 3 years after diagnosis. After adjusting for age, sex, year, medical insurance coverage, and population group, opioid-related disorders were associated with an increased risk of mortality (aHR 2.28, 95% CI 1.84-2.82). Opioid-related disorders were associated with a 7.8-year shorter life expectancy. CONCLUSIONS: The incidence of people diagnosed with or treated for an opioid-related disorder in the private sector is increasing rapidly. People with opioid-related disorders are a vulnerable population with substantial psychiatric comorbidity who often die prematurely. Evidence-based management of opioid-related disorders is urgently needed to improve the health outcomes of people with opioid-related disorders.

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).

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.

The effect of the COVID-19 lockdown on mental health care use in South Africa: an interrupted time-series analysis.

AIMS: The coronavirus disease 2019 (COVID-19) pandemic and ensuing restrictions have negatively affected the mental health and well-being of the general population, and there is increasing evidence suggesting that lockdowns have led to a disruption of health services. In March 2020, South Africa introduced a lockdown in response to the COVID-19 pandemic, entailing the suspension of all non-essential activities and a complete ban of tobacco and alcohol sales. We studied the effect of the lockdown on mental health care utilisation rates in private-sector care in South Africa. METHODS: We conducted an interrupted time-series analysis using insurance claims from 1 January 2017 to 1 June 2020 of beneficiaries 18 years or older from a large private sector medical insurance scheme. We calculated weekly outpatient consultation and hospital admission rates for organic mental disorders, substance use disorders, serious mental disorders, depression, anxiety, other mental disorders, any mental disorder and alcohol withdrawal syndrome. We calculated adjusted odds ratios (OR) for the effect of the lockdown on weekly outpatient consultation and hospital admission rates and the weekly change in rates during the lockdown until 1 June 2020. RESULTS: 710 367 persons were followed up for a median of 153 weeks. Hospital admission rates (OR 0.38; 95% confidence interval (CI) 0.33-0.44) and outpatient consultation rates (OR 0.74; 95% CI 0.63-0.87) for any mental disorder decreased substantially after the introduction of the lockdown and did not recover to pre-lockdown levels by 1 June 2020. Health care utilisation rates for alcohol withdrawal syndrome doubled after the introduction of the lockdown, but the statistical uncertainty around the estimates was large (OR 2.24; 95% CI 0.69-7.24). CONCLUSIONS: Mental health care utilisation rates for inpatient and outpatient services decreased substantially after the introduction of the lockdown. Hospital admissions and outpatient consultations for alcohol withdrawal syndrome increased after the introduction of the lockdown, but statistical uncertainty precludes strong conclusions about a potential unintended effect of the alcohol sales ban. Governments should integrate strategies for ensuring access and continuity of essential mental health services during lockdowns in pandemic preparedness planning.

Mental health of migrants with pre-migration exposure to armed conflict: a systematic review and meta-analysis.

BACKGROUND: Exposure to armed conflict has been associated with negative mental health consequences. We aimed to estimate the prevalence of generalised anxiety disorder, major depressive disorder, and post-traumatic stress disorder among migrants exposed to armed conflict. METHODS: In this systematic review and meta-analysis, we searched online databases (Cochrane Library, Embase, LILACS, PsycInfo [via Ovid], PubMed, and Web of Science Core Collection) for relevant observational studies published between Jan 1, 1994, and June 28, 2021. We included studies that used standardised psychiatric interviews to assess generalised anxiety disorder, major depressive disorder, or post-traumatic stress disorder among migrants (refugees or internally displaced persons; aged ≥18 years) with pre-migration exposure to armed conflict. We excluded studies in which exposure to armed conflict could not be ascertained, studies that included a clinical population or people with chronic diseases that can trigger the onset of mental disease, and studies published before 1994. We used a random effects model to estimate each mental health disorder's pooled prevalence and random effects meta-regression to assess sources of heterogeneity. Two independent reviewers assessed the risk of bias for each study using the Joanna Briggs Institute Checklist for Prevalence Studies. The protocol was registered with PROSPERO, CRD42020209251. FINDINGS: Of the 13 935 studies identified, 34 met our inclusion criteria; these studies accounted for 15 549 migrants. We estimated a prevalence of current post-traumatic stress disorder of 31% (95% CI 23-40); prevalence of current major depressive disorder of 25% (17-34); and prevalence of generalised anxiety disorder of 14% (5-35). Younger age was associated with a higher prevalence of current post-traumatic stress disorder (odds ratio 0·95 [95% CI 0·90-0·99]), lifetime post-traumatic stress disorder (0·88 [0·83-0·92]), and current generalised anxiety disorder (0·87 [0·78-0·97]). A longer time since displacement was associated with a lower lifetime prevalence of post-traumatic stress disorder (0·88 [0·81-0·95]) and major depressive disorder (0·81 [0·77-0·86]). Migrating to a middle-income (8·09 [3·06-21·40]) or low-income (39·29 [11·96-129·70]) country was associated with increased prevalence of generalised anxiety disorder. INTERPRETATION: Migrants who are exposed to armed conflict are at high risk of mental health disorders. The mental health-care needs of migrants should be assessed soon after resettlement, and adequate care should be provided, with particular attention paid to young adults. FUNDING: Marie Sklodowska-Curie Actions (Horizon 2020-COFUND), MinCiencias (Colombia), and Swiss National Science Foundation.

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.

Prevalence of and factors associated with late diagnosis of HIV in Malawi, Zambia, and Zimbabwe: Results from population-based nationally representative surveys.

INTRODUCTION: Late diagnosis of HIV (LD) increases the risk of morbidity, mortality, and HIV transmission. We used nationally representative data from population-based HIV impact assessment (PHIA) surveys in Malawi, Zambia, and Zimbabwe (2015-2016) to characterize adults at risk of LD and to examine associations between LD and presumed HIV transmission to cohabiting sexual partners. METHODS: We estimated the prevalence of LD, defined as CD4 count <350 cells/µL, among adults newly diagnosed with HIV during the surveys and odds ratios for associated factors. We linked newly diagnosed adults (index cases) to their household sexual partners and calculated adjusted odds ratios for associations between LD of the index case, viral load of the index case, and duration of HIV exposure in the relationship, and the HIV status of the household sexual partner. RESULTS: Of 1,804 adults who were newly diagnosed with HIV in the surveys, 49% (882) were diagnosed late. LD was associated with male sex, older age, and almost five times the odds of having an HIV-positive household sexual partner (adjusted odds ratio [aOR], 4.65 [95% confidence interval: 2.56-8.45]). Longer duration of HIV exposure in a relationship and higher viral load of the index case were both independently associated with higher odds of having HIV-positive household sexual partners. Individuals with HIV exposure of more than 5 years had more than three times (aOR 3.42 [95% CI: 1.63-7.18]) higher odds of being HIV positive than those with less than 2 years HIV exposure. The odds of being HIV positive were increased in individuals who were in a relationship with an index case with a viral load of 400-3499 copies/mL (aOR 4.06 [95% CI 0.45-36.46]), 3,500-9,999 copies/mL (aOR 11.32 [95% CI: 4.08-31.39]), 10,000-49,999 copies/mL (aOR 17.07 [95% CI: 9.18-31.72]), and ≥50,000 copies/mL (aOR 28.41 [95% CI: 12.18-66.28]) compared to individuals who were in a relationship with an index case with a viral load of <400 copies/mL. CONCLUSIONS: LD remains a challenge in Southern Africa and is strongly associated with presumed HIV transmission to household sexual partners. Our study underscores the need for earlier HIV diagnosis, particularly among men and older adults, and the importance of index testing.

Symptoms of common mental disorders and adherence to antiretroviral therapy among adults living with HIV in rural Zimbabwe: a cross-sectional study.

OBJECTIVES: To examine the proportion of people living with HIV who screen positive for common mental disorders (CMD) and the associations between CMD and self-reported adherence to antiretroviral therapy (ART). SETTING: Sixteen government-funded health facilities in the rural Bikita district of Zimbabwe. DESIGN: Cross-sectional study. PARTICIPANTS: HIV-positive non-pregnant adults, aged 18 years or older, who lived in Bikita district and had received ART for at least 6 months. OUTCOME MEASURES: The primary outcome was the proportion of participants screening positive for CMD defined as a Shona Symptoms Questionnaire score of 9 or greater. Secondary outcomes were the proportion of participants reporting suicidal ideation, perceptual symptoms and suboptimal ART adherence and adjusted prevalence ratios (aPR) for factors associated with CMD, suicidal ideation, perceptual symptoms and suboptimal ART adherence. RESULTS: Out of 3480 adults, 18.8% (95% CI 14.8% to 23.7%) screened positive for CMD, 2.7% (95% CI 1.5% to 4.7%) reported suicidal ideations, and 1.5% (95% CI 0.9% to 2.6%) reported perceptual symptoms. Positive CMD screens were more common in women (aPR 1.67, 95% CI 1.19 to 2.35) than in men and were more common in adults aged 40-49 years (aPR 1.47, 95% CI 1.16 to 1.85) or aged 50-59 years (aPR 1.51, 95% CI 1.05 to 2.17) than in those 60 years or older. Positive CMD screen was associated with suboptimal adherence (aPR 1.53; 95% CI 1.37 to 1.70). CONCLUSIONS: A substantial proportion of people living with HIV in rural Zimbabwe are affected by CMD. There is a need to integrate mental health services and HIV programmes in rural Zimbabwe. TRIAL REGISTRATION NUMBER: NCT03704805.