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.

Availability of substance use screening and treatment within HIV clinical sites across seven geographic regions within the IeDEA consortium.

BACKGROUND: Overwhelming evidence highlights the negative impact of substance use on HIV care and treatment outcomes. Yet, the extent to which alcohol use disorder (AUD) and other substance use disorders (SUD) services have been integrated within HIV clinical settings is limited. We describe AUD/SUD screening and treatment availability in HIV clinical sites participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. METHODS: In 2020, 223 IeDEA HIV clinical sites from 41 countries across seven geographic regions completed a survey on capacity and practices related to management of AUD/ SUD. Sites provided information on AUD and other SUD screening and treatment practices. RESULTS: Sites were from low-income countries (23%), lower-middle-income countries (38%), upper-middle income countries (17%) and high-income counties (23%). AUD and SUD screening using validated instruments were reported at 32% (n=71 located in 12 countries) and 12% (n=27 located in 6 countries) of the 223 sites from 41 countries, respectively. The North American region had the highest proportion of clinics that reported AUD screening (76%), followed by East Africa (46%); none of the sites in West or Central Africa reported AUD screening. 31% (n=69) reported both AUD screening and counseling, brief intervention, psychotherapy, or Screening, Brief Intervention, and Referral to Treatment; 8% (n=18) reported AUD screening and detox hospitalization; and 10% (n=24) reported both AUD screening and medication. While the proportion of clinics providing treatment for SUD was lower than those treating AUD, the prevalence estimates of treatment availability were similar. CONCLUSIONS: Availability of screening and treatment for AUD/SUD in HIV care settings is limited, leaving a substantial gap for integration into ongoing HIV care. A critical understanding is needed of the multilevel implementation factors or feasible implementation strategies for integrating screening and treatment of AUD/SUD into HIV care settings, particularly for resource-constrained regions.

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.

An agent-based model of binge drinking, inequitable gender norms and their contribution to HIV transmission, with application to South Africa.

BACKGROUND: Binge drinking, inequitable gender norms and sexual risk behaviour are closely interlinked. This study aims to model the potential effect of alcohol counselling interventions (in men and women) and gender-transformative interventions (in men) as strategies to reduce HIV transmission. METHODS: We developed an agent-based model of HIV and other sexually transmitted infections, allowing for effects of binge drinking on sexual risk behaviour, and effects of inequitable gender norms (in men) on sexual risk behaviour and binge drinking. The model was applied to South Africa and was calibrated using data from randomized controlled trials of alcohol counselling interventions (n = 9) and gender-transformative interventions (n = 4) in sub-Saharan Africa. The model was also calibrated to South African data on alcohol consumption and acceptance of inequitable gender norms. Binge drinking was defined as five or more drinks on a single day, in the last month. RESULTS: Binge drinking is estimated to be highly prevalent in South Africa (54% in men and 35% in women, in 2021), and over the 2000-2021 period 54% (95% CI: 34-74%) of new HIV infections occurred in binge drinkers. Binge drinking accounted for 6.8% of new HIV infections (0.0-32.1%) over the same period, which was mediated mainly by an effect of binge drinking in women on engaging in casual sex. Inequitable gender norms accounted for 17.5% of incident HIV infections (0.0-68.3%), which was mediated mainly by an effect of inequitable gender norms on male partner concurrency. A multi-session alcohol counselling intervention that reaches all binge drinkers would reduce HIV incidence by 1.2% (0.0-2.5%) over a 5-year period, while a community-based gender-transformative intervention would reduce incidence by 3.2% (0.8-7.2%) or by 7.3% (0.6-21.2%) if there was no waning of intervention impact. CONCLUSIONS: Although binge drinking and inequitable gender norms contribute substantially to HIV transmission in South Africa, recently-trialled alcohol counselling and gender-transformative interventions are likely to have only modest effects on HIV incidence. Further innovation in developing locally-relevant interventions to address binge drinking and inequitable gender norms is needed.

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.

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.

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.

Risk Factors for Hospitalization or Death Among Adults With Advanced HIV at Enrollment for Care in South Africa: A Secondary Analysis of the TB Fast Track Trial.

Background: Individuals with advanced HIV experience high mortality, especially before and during the first months of antiretroviral therapy (ART). We aimed to identify factors, measurable in routine, primary health clinic-based services, associated with the greatest risk of poor outcome. Methods: We included all individuals enrolled in the standard-of-care arm of a cluster-randomized trial (TB Fast Track); adults attending participating health clinics with CD4 ≤150 cells/µL and no recent ART were eligible. Associations between baseline exposures and a composite outcome (hospitalization/death) over 6 months were estimated using multivariable Cox regression. Results: Among 1515 individuals (12 clinics), 56% were female, the median age was 36 years, and the median CD4 count was 70 cells/µL. Within 6 months, 89% started ART. The overall rate of hospitalization/death was 32.5 per 100 person-years (218 outcomes/671 person-years). Lower baseline CD4 count (adjusted hazard ratio [aHR], 2.27 for <50 vs 100-150 cells/µL; 95% CI, 1.57-3.27), lower body mass index (aHR, 2.13 for BMI <17 vs ≥25 kg/m2; 95% CI, 1.31-3.45), presence of tuberculosis-related symptoms (aHR, 1.87 for 3-4 symptoms vs none; 95% CI, 1.20-2.93), detectable urine lipoarabinomannan (aHR, 1.97 for 1+ positivity vs negative; 95% CI, 1.37-2.83), and anemia (aHR, 4.42 for severe anemia [hemoglobin <8 g/dL] vs none; 95% CI, CI 2.38-8.21) were strong independent risk factors for hospitalization/death. Conclusions: Simple measures that can be routinely assessed in primary health care in resource-limited settings identify individuals with advanced HIV at high risk of poor outcomes; these may guide targeted interventions to improve outcomes.

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.

Causes and Outcomes of Admission and Investigation of Tuberculosis in Adults with Advanced HIV in South African Hospitals: Data from the TB Fast Track Trial.

Tuberculosis (TB) remains the leading cause of hospitalization and in-hospital mortality in HIV-positive adults. Using data from hospital and clinic files, research databases, and autopsy, we describe causes and outcomes of admissions, and assess investigations for TB among adults with advanced HIV who were hospitalized after enrollment into the TB Fast Track trial in South Africa (2013-2015). A total of 251 adults [median CD4 count, 37.5 cells/µL; interquartile range, 14-68 cells/µL; 152 (60.6%) on antiretroviral therapy] experienced 304 admissions. Ninety-five of 251 of the first admissions (37.8%) were TB related; the next most common causes were AIDS-related illnesses (41 of 251, 16.3%) and surgical causes (21 of 251, 8.4%). Of those admitted with previously undiagnosed TB, 60% had CD4 counts less than 50 cells/µL. Overall, 137 of 251 individuals died as inpatients or within 90 days of their first discharge. Case fatality rates were particularly high for those admitted with TB (66%) and bacterial infections (80%). In 144 admissions for whom anti-TB treatment had not been started before admission, a sputum-based TB investigation was recorded in only 12 of 57 admissions (21.1%) in whom one or more TB symptom was recorded (24 of 57 started on treatment), and 6 of 87 admissions (6.9%) in whom no TB symptoms were recorded (14 of 87 started on treatment). Hospitalized adults with advanced HIV are at high risk of death. TB was a common cause of hospitalization but was under-investigated, even in those with symptoms. In addition to early identification of TB and other AIDS-related illnesses during hospitalization of adults with advanced HIV, improved pre-hospital management strategies are needed to interrupt disease progression and reduce poor outcomes in this already vulnerable population.

Evidence for the Use of Triage, Respiratory Isolation, and Effective Treatment to Reduce the Transmission of Mycobacterium Tuberculosis in Healthcare Settings: A Systematic Review.

Evidence is limited for infection prevention and control (IPC) measures reducing Mycobacterium tuberculosis (MTB) transmission in health facilities. This systematic review, 1 of 7 commissioned by the World Health Organization to inform the 2019 update of global tuberculosis (TB) IPC guidelines, asked: do triage and/or isolation and/or effective treatment of TB disease reduce MTB transmission in healthcare settings? Of 25 included articles, 19 reported latent TB infection (LTBI) incidence in healthcare workers (HCWs; absolute risk reductions 1%-21%); 5 reported TB disease incidence in HCWs (no/slight [high TB burden] or moderate [low burden] reduction) and 2 in human immunodeficiency virus-positive in-patients (6%-29% reduction). In total, 23/25 studies implemented multiple IPC measures; effects of individual measures could not be disaggregated. Packages of IPC measures appeared to reduce MTB transmission, but evidence for effectiveness of triage, isolation, or effective treatment, alone or in combination, was indirect and low quality. Harmonizing study designs and reporting frameworks will permit formal data syntheses and facilitate policy making.

Mental health, substance use and viral suppression in adolescents receiving ART at a paediatric HIV clinic in South Africa.

INTRODUCTION: Mental health problems are prevalent in adolescents living with HIV (ALHIV), often remain untreated, and may negatively affect antiretroviral therapy (ART) adherence and viral suppression. We implemented routine mental health screening at a paediatric ART clinic to improve the identification and management of mental health problems in ALHIV. In this report, we examine screening outcomes, associated patient characteristics and the odds of unsuppressed viral load in ALHIV screening positive for mental disorders. METHODS: Adolescents aged 10 to 19 years attending Rahima Moosa Hospital in Johannesburg, South Africa between February 1, 2018, and January 1, 2020, were offered mental health screening at each routine HIV care visit. The screening included four pre-screening questions followed by full screening (conditional on positive pre-screening) for depression (Patient Health Questionnaire-9 [PHQ-9]), suicide (Adolescent Innovations Project [AIP]-handbook), anxiety (Generalized Anxiety Disorder-7 [GAD-7]), post-traumatic stress disorder (PTSD) (Primary Care PTSD Screen [PC-PTSD-5]) and substance use (CAGE Adapted to Include Drugs [CAGE-AID]). We assessed screening outcomes and calculated adjusted odds ratios for associations between positive screening tests at the first screen and unsuppressed viral load (>400 copies/mL) at the measurement taken closest to the date of screening, within hundred days before and one day after screening. RESULTS: Out of 1203 adolescents who attended the clinic, 1088 (90.4%) were pre-screened of whom 381 (35.0%) underwent full screening, 48 (4.4%) screened positive for depression (PHQ-9 ≥10), 29 (2.8%) for suicidal concern, 24 (2.2%) for anxiety (GAD-7 ≥10), 38 (3.2%) for PTSD (PC-PTSD-5 ≥3), 18 (1.7%) for substance use (CAGE-AID ≥2) and 97 (8.9%) for any of these conditions. Positive screening for depression (aOR 2.39, 95% CI 1.02 to 5.62), PTSD (aOR 3.18, 95% CI 1.11 to 9.07), substance use (aOR 7.13, 95% CI 1.60 to 31.86), or any condition (aOR 2.17, 95% CI 1.17 to 4.02) were strongly associated with unsuppressed viral load. CONCLUSIONS: ALHIV affected by mental health problems have increased rates of unsuppressed viral load and need specific clinical attention. The integration of routine mental health screening in paediatric ART programmes is a feasible approach for identifying and referring adolescents with mental health and adherence problems to counselling and psychosocial support services and if needed to psychiatric care.

Excess mortality associated with mental illness in people living with HIV in Cape Town, South Africa: a cohort study using linked electronic health records.

BACKGROUND: Mental disorders can adversely affect HIV treatment outcomes and survival. Data are scarce on premature deaths in people with mental disorders in HIV-positive populations, particularly in low-income and middle-income countries. In this study, we quantified excess mortality associated with mental disorders in HIV-positive people in South Africa, adjusting for HIV treatment outcomes. METHODS: For this cohort study, we analysed routinely collected data on HIV-positive adults receiving antiretroviral therapy (ART) in Cape Town, South Africa between Jan 1, 2004, to Dec 31, 2017. Data from three ART programmes were linked with routine medical records on mental health treatment from Jan 1, 2010, to Dec 31, 2017, and mortality surveillance data from the South African National Population Register up to Dec 31, 2017. People living with HIV aged 15 years or older who initiated ART at a programme site were eligible for analysis. We followed up patients from ART initiation or Jan 1, 2010, whichever occurred later, to transfer, death, or Dec 31, 2017. Patients were considered as having a history of mental illness if they had ever received psychiatric medication or been hospitalised for a mental disorder. We calculated adjusted hazard ratios (aHRs) with 95% CIs for associations between history of mental illness, mortality, and HIV treatment outcomes (retention in care with viral load suppression [VLS; viral load <1000 copies per mL], retention in care with non-suppressed viral load [NVL; viral load ≥1000 copies per mL], and loss to follow-up [LTFU; >180 days late for a clinic visit at closure of the database]) using Cox proportional hazard regression and multistate models. RESULTS: 58 664 patients were followed up for a median of 4·3 years (IQR 2·1-6·4), 2927 (5·0%) of whom had a history of mental illness. After adjustment for age, sex, treatment programme, and year of ART initiation, history of mental illness was associated with increased risk of mortality from all causes (aHR 2·98 [95% CI 2·69-3·30]), natural causes (3·00 [2·69-3·36]), and unnatural causes (2·10 [1·27-3·49]), compared with no history of mental illness. Risk of all-cause mortality in people with a history of mental illness remained increased in multivariable analysis adjusted for age, sex, treatment programme, year of ART initiation, CD4 count and WHO clinical stage at ART initiation, retention in HIV care with or without VLS, and LTFU (2·73 [2·46-3·02]). In our multistate model, adjusted for age, sex, year of ART initiation, cumulative time with NVL, and WHO clinical stage and CD4 cell count at ART initiation, rates of excess all-cause mortality in people with history of mental illness were greatest in patients retained in care with VLS (aHR 3·43 [95% CI 2·83-4·15]), followed by patients retained in care with NVL (2·74 [2·32-3·24]), and smallest in those LTFU (2·12 [1·78-2·53]). History of mental illness was also associated with increased risk of HIV viral rebound (transitioning from VLS to NVL; 1·50 [1·32-1·69]) and LTFU in people with VLS (1·19 [1·06-1·34]). INTERPRETATION: Mental illness was associated with substantial excess mortality in HIV-positive adults in Cape Town. Excess mortality among people with a history of mental illness occurred independently of HIV treatment success. Interventions to reduce excess mortality should address the complex physical and mental health-care needs of people living with HIV and mental illness. FUNDING: National Institutes of Health, Swiss National Science Foundation, South African Medical Research Council.

Substance use service availability in HIV treatment programs: Data from the global IeDEA consortium, 2014-2015 and 2017.

BACKGROUND: Substance use is common among people living with HIV and has been associated with suboptimal HIV treatment outcomes. Integrating substance use services into HIV care is a promising strategy to improve patient outcomes. METHODS: We report on substance use education, screening, and referral practices from two surveys of HIV care and treatment sites participating in the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. HIV care and treatment sites participating in IeDEA are primarily public-sector health facilities and include both academic and community-based hospitals and health facilities. A total of 286 sites in 45 countries participated in the 2014-2015 survey and 237 sites in 44 countries participated in the 2017 survey. We compared changes over time for 147 sites that participated in both surveys. RESULTS: In 2014-2015, most sites (75%) reported providing substance use-related education on-site (i.e., at the HIV clinic or the same health facility). Approximately half reported on-site screening for substance use (52%) or referrals for substance use treatment (51%). In 2017, the proportion of sites providing on-site substance use-related education, screening, or referrals increased by 9%, 16%, and 8%, respectively. In 2017, on-site substance use screening and referral were most commonly reported at sites serving only adults (compared to only children/adolescents or adults and children/adolescents; screening: 86%, 37%, and 59%, respectively; referral: 76%, 47%, and 46%, respectively) and at sites in high-income countries (compared to upper middle income, lower middle income or low-income countries; screening: 89%, 76%, 68%, and 45%, respectively; referral: 82%, 71%, 57%, and 34%, respectively). CONCLUSION: Although there have been increases in the proportion of sites reporting substance use education, screening, and referral services across IeDEA sites, gaps persist in the integration of substance use services into HIV care, particularly in relation to screening and referral practices, with reduced availability for children/adolescents and those receiving care within resource-constrained settings.

Universal test-and-treat in Zambian and South African correctional facilities: a multisite prospective cohort study.

BACKGROUND: Despite the global scale-up of antiretroviral therapy (ART), incarcerated people have not benefited equally from test-and-treat recommendations for HIV. To improve access to ART for incarcerated people with HIV, we introduced a universal test-and-treat (UTT) intervention in correctional facilities in South Africa and Zambia, and aimed to assess UTT feasibility and clinical outcomes. METHODS: Treatment as Prevention (TasP) was a multisite, mixed methods, implementation research study done at three correctional complexes in South Africa (Johnannesburg and Breede River) and Zambia (Lusaka). Here, we report the clinical outcomes for a prospective cohort of incarcerated individuals who were offered the TasP UTT intervention. Incarcerated individuals were eligible for inclusion if they were aged 18 years or older, with new or previously diagnosed HIV, not yet on ART, and were expected to remain incarcerated for 30 days or longer. To enable the implementation of UTT at the included correctional facilities, we first strengthened on-site HIV service delivery. All participants were offered same-day ART initiation, and had two study-specific follow-up visits scheduled to coincide with routine clinic visits at 6 and 12 months. The main outcomes were ART uptake, time from cohort enrolment to ART initiation, and retention in care and viral suppression at 6 and 12 months. We estimated the association between baseline demographic characteristics and time to ART initiation using Cox proportional hazard models, and, in a post-hoc analysis, we used logistic regression models to assess the association between demographic and clinical variables, including time to ART initiation, and the proportion of participants with a composite poor outcome (defined as viral load >50 copies per mL, or for participants with a missing viral load, lack of retention in care in the on-site ART programme) at 6 months. This study is registered at ClinicalTrials.gov, NCT02946762. FINDINGS: Between June 23, 2016, and Dec 31, 2017, we identified 1562 incarcerated people with HIV, of whom 1389 (89%) were screened, 1021 (74%) met eligibility criteria, and 975 (95%) were enrolled and followed up to March 31, 2018. At the end of follow-up, 835 (86%) of 975 participants had started ART. Median time from enrolment to ART initiation was 0 days (IQR 0-8). Of 346 participants who remained incarcerated at 6 months, 327 (95%) were retained in care and 269 (78%) had a documented viral load, of whom 262 (97%) achieved viral suppression (<1000 copies per mL). The mortality rate among the 835 participants who had initiated ART was 1·9 per 100 person-years (95% CI 0·9-3·9). No statistically significant associations were identified between any baseline characteristics and time to ART initiation or composite poor outcome. INTERPRETATION: UTT implementation is feasible in correctional settings, and can achieve levels of same-day ART uptake, retention in care, and viral suppression among incarcerated people with HIV that are comparable to those observed in community settings. FUNDING: UK Department for International Development, Swedish International Development Cooperation Agency, Norwegian Agency for Development Cooperation.

Sensitivity of the lateral flow urine lipoarabinomannan assay in ambulant adults with advanced HIV disease: data from the TB Fast Track study.

BACKGROUND: WHO guidelines recommend the lateral flow urine lipoarabinomannan assay (LF-LAM) for TB diagnosis in hospitalised HIV-positive individuals. The role of LF-LAM among ambulant patients remains less well defined. We investigated the sensitivity of LF-LAM among ambulant HIV-positive adults in primary health clinics in South Africa. METHODS: We enrolled adults (aged ≥18 y) with CD4 counts of ≤150 cells/mm3 who had not received TB treatment or antiretroviral therapy in the preceding 3 or 6 mo, respectively. Research nurses performed the LF-LAM test on freshly voided urine. Results were compared with a reference standard of positive mycobacterial culture (sputum or urine). RESULTS: Of 1505 (54.5% female; median age 37 y; median CD4 count 73 cells/mm3) participants, 973 (64.7%) had a mycobacterial culture result; 105/973 (10.8%) were positive for Mycobacterium tuberculosis. LF-LAM sensitivity was 41.9% (95% CI 32.3 to 51.9%) and 19.0% (95% CI 12.0 to 27.9%) using grade 1+ and grade 2+ cut-off points, respectively. Sensitivity increased with severe immunosuppression and in the presence of poor prognostic indicators (low haemoglobin, body mass index). CONCLUSIONS: When used as the only TB diagnostic test, LF-LAM sensitivity is suboptimal, particularly using the grade 2+ cut-off. More sensitive tests for TB are needed that can be used in primary care settings.

Algorithm-guided empirical tuberculosis treatment for people with advanced HIV (TB Fast Track): an open-label, cluster-randomised trial.

BACKGROUND: Tuberculosis, which is often undiagnosed, is the major cause of death among HIV-positive people. We aimed to test whether the use of a clinical algorithm enabling the initiation of empirical tuberculosis treatment by nurses in primary health-care clinics would reduce mortality compared with standard of care for adults with advanced HIV disease. METHODS: In this open-label cluster-randomised controlled trial, we recruited individuals from 24 primary health-care clinics in South Africa. The clinics were randomly assigned (1:1) to either deliver an intervention or routine care (control) using computer-generated random numbers. Eligible participants were HIV-positive adults (aged ≥18 years) with CD4 counts of 150 cells per µL or less, who had not had antiretroviral therapy (ART) in the past 6 months or tuberculosis treatment in the past 3 months, and did not require urgent hospital referral. In intervention clinics, study nurses assessed participants on the basis of tuberculosis symptoms, body-mass index, point-of-care haemoglobin concentrations, and urine lipoarabinomannan assay results. Participants classified by a study algorithm as having high probability of tuberculosis (positive urine lipoarabinomannan assay, body-mass index <18·5 kg/m2, or haemoglobin concentration <100 g/L) were recommended to start tuberculosis treatment immediately followed by ART 2 weeks later; participants classified as medium probability (tuberculosis symptoms, no high probability criteria) were recommended to have symptom-guided investigation; and participants classified as low probability (no tuberculosis symptoms or high probability criteria) were recommended to start ART immediately. In standard-of-care clinics, participants received treatment in accordance with South African guidelines. Investigators and participants were aware of treatment allocation. The primary outcome was all-cause mortality at 6 months, assessed in the intention-to-treat population. Safety was also analysed in the intention-to treat population. This trial is registered with the ISRCTN registry, ISRCTN35344604, and the South African National Clinical Trials Register, DOH-27-0812-3902. FINDINGS: Between Dec 19, 2012, and Dec 18, 2014, 3091 individuals were screened for eligibility, of whom 3053 were recruited, and 3022 (1507 participants in the intervention group and 1515 participants in the control group) were analysed for the primary outcome. 930 (61·7%) of 1507 participants in the intervention group versus 172 (11·4%) of 1515 participants in the control group had started tuberculosis treatment by 2 months. At 6 months, the mortality rate was 19·0 deaths per 100 person-years for the intervention group versus 21·6 deaths per 100 person-years in the control group (unadjusted hazard ratio [HR] 0·92, 95% CI 0·67-1·26, p=0·58; adjusted HR 0·87, 0·61-1·24, p=0·41). 28 (1·9%) of 1507 participants in the intervention group and ten (0·7%) of 1515 participants in the control group reported serious or severe adverse events. Grade 3 or 4 nausea and vomiting was the most common adverse event (ten participants in the intervention group and four participants in the control group). Among participants with adverse events, eight participants (six participants in the intervention group and two participants in the control group) died; none of the six deaths in the intervention group were attributed to the study intervention. INTERPRETATION: Our intervention substantially increased coverage of tuberculosis treatment in this high-risk population, but did not reduce mortality. FUNDING: Joint Global Health Trials (Medical Research Council, Department for International Development, Wellcome Trust).

Performance of verbal autopsy methods in estimating HIV-associated mortality among adults in South Africa.

INTRODUCTION: Verbal autopsy (VA) can be integrated into civil registration and vital statistics systems, but its accuracy in determining HIV-associated causes of death (CoD) is uncertain. We assessed the sensitivity and specificity of VA questions in determining HIV status and antiretroviral therapy (ART) initiation and compared HIV-associated mortality fractions assigned by different VA interpretation methods. METHODS: Using the WHO 2012 instrument with added ART questions, VA was conducted for deaths among adults with known HIV status (356 HIV positive and 103 HIV negative) in South Africa. CoD were assigned using physician-certified VA (PCVA) and computer-coded VA (CCVA) methods and compared with documented HIV status. RESULTS: The sensitivity of VA questions in detecting HIV status and ART initiation was 84.3% (95% CI 80 to 88) and 91.0% (95% CI 86 to 95); 283/356 (79.5%) HIV-positive individuals were assigned HIV-associated CoD by PCVA, 166 (46.6%) by InterVA-4.03, 201 (56.5%) by InterVA-5, and 80 (22.5%) and 289 (81.2%) by SmartVA-Analyze V.1.1.1 and V.1.2.1. Agreement between PCVA and older CCVA methods was poor (chance-corrected concordance [CCC] <0; cause-specific mortality fraction [CSMF] accuracy ≤56%) but better between PCVA and updated methods (CCC 0.21-0.75; CSMF accuracy 65%-98%). All methods were specific (specificity 87% to 96%) in assigning HIV-associated CoD. CONCLUSION: All CCVA interpretation methods underestimated the HIV-associated mortality fraction compared with PCVA; InterVA-5 and SmartVA-Analyze V.1.2.1 performed better than earlier versions. Changes to VA methods and classification systems are needed to track progress towards targets for reducing HIV-associated mortality.

Measuring mortality due to HIV-associated tuberculosis among adults in South Africa: Comparing verbal autopsy, minimally-invasive autopsy, and research data.

BACKGROUND: The World Health Organization (WHO) aims to reduce tuberculosis (TB) deaths by 95% by 2035; tracking progress requires accurate measurement of TB mortality. International Classification of Diseases (ICD) codes do not differentiate between HIV-associated TB and HIV more generally. Verbal autopsy (VA) is used to estimate cause of death (CoD) patterns but has mostly been validated against a suboptimal gold standard for HIV and TB. This study, conducted among HIV-positive adults, aimed to estimate the accuracy of VA in ascertaining TB and HIV CoD when compared to a reference standard derived from a variety of clinical sources including, in some, minimally-invasive autopsy (MIA). METHODS AND FINDINGS: Decedents were enrolled into a trial of empirical TB treatment or a cohort exploring diagnostic algorithms for TB in South Africa. The WHO 2012 instrument was used; VA CoD were assigned using physician-certified VA (PCVA), InterVA-4, and SmartVA-Analyze. Reference CoD were assigned using MIA, research, and health facility data, as available. 259 VAs were completed: 147 (57%) decedents were female; median age was 39 (interquartile range [IQR] 33-47) years and CD4 count 51 (IQR 22-102) cells/µL. Compared to reference CoD that included MIA (n = 34), VA underestimated mortality due to HIV/AIDS (94% reference, 74% PCVA, 47% InterVA-4, and 41% SmartVA-Analyze; chance-corrected concordance [CCC] 0.71, 0.42, and 0.31, respectively) and HIV-associated TB (41% reference, 32% PCVA; CCC 0.23). For individual decedents, all VA methods agreed poorly with reference CoD that did not include MIA (n = 259; overall CCC 0.14, 0.06, and 0.15 for PCVA, InterVA-4, and SmartVA-Analyze); agreement was better at population level (cause-specific mortality fraction accuracy 0.78, 0.61, and 0.57, for the three methods, respectively). CONCLUSIONS: Current VA methods underestimate mortality due to HIV-associated TB. ICD and VA methods need modifications that allow for more specific evaluation of HIV-related deaths and direct estimation of mortality due to HIV-associated TB.