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.

Correcting mortality estimates among children and youth on antiretroviral therapy in southern Africa: A comparative analysis between a multi-country tracing study and linkage to a health information exchange.

OBJECTIVES: The objective of this study is to assess the outcomes of children, adolescents and young adults with HIV reported as lost to follow-up, correct mortality estimates for children, adolescents and young adults with HIV for unascertained outcomes in those loss to follow-up (LTFU) based on tracing and linkage data separately using data from the International epidemiology Databases to Evaluate AIDS in Southern Africa. METHODS: We included data from two different populations of children, adolescents and young adults with HIV; (1) clinical data from children, adolescents and young adults with HIV aged ≤24 years from Lesotho, Malawi, Mozambique, Zambia and Zimbabwe; (2) clinical data from children, adolescents and young adults with HIV aged ≤14 years from the Western Cape (WC) in South Africa. Outcomes of patients lost to follow-up were available from (1) a tracing study and (2) linkage to a health information exchange. For both populations, we compared six methods for correcting mortality estimates for all children, adolescents and young adults with HIV. RESULTS: We found substantial variations of mortality estimates among children, adolescents and young adults with HIV reported as lost to follow-up versus those retained in care. Ascertained mortality was higher among lost and traceable children, adolescents and young adults with HIV and lower among lost and linkable than those retained in care (mortality: 13.4% [traced] vs. 12.6% [retained-other Southern Africa countries]; 3.4% [linked] vs. 9.4% [retained-WC]). A high proportion of lost to follow-up children, adolescents and young adults with HIV had self-transferred (21.0% and 47.0%) in the traced and linked samples, respectively. The uncorrected method of non-informative censoring yielded the lowest mortality estimates among all methods for both tracing (6.0%) and linkage (4.0%) approaches at 2 years from ART start. Among corrected methods using ascertained data, multiple imputation, incorporating ascertained data (MI(asc.)) and inverse probability weighting with logistic weights were most robust for the tracing approach. In contrast, for the linkage approach, MI(asc.) was the most robust. CONCLUSIONS: Our findings emphasise that lost to follow-up is non-ignorable and both tracing and linkage improved outcome ascertainment: tracing identified substantial mortality in those reported as lost to follow-up, whereas linkage did not identify out-of-facility deaths, but showed that a large proportion of those reported as lost to follow-up were self-transfers.

Men's Satisfaction with General Health Services is Associated with Future Use of HIV Testing in Malawi: A Community-Representative Survey.

Across sub-Saharan Africa, men are less likely to know their HIV status than women, leading to later treatment initiation. Little is known about how experiences with general health services affect men's use of HIV testing. We used data from a 2019 community-representative survey of men in Malawi to understand frequency and cause of men's negative health service experiences (defined as men reporting they "would not recommend" a facility) and their association with future HIV testing. We conducted univariable and multivariable logistic regressions to determine which aspects of health facility visits were associated with would-not-recommend experiences and to determine if would-not-recommend experiences 12-24 months prior to the survey were associated with HIV testing in the 12 months prior to the survey. Among 1,098 men eligible for HIV testing in the 12 months prior to the survey, median age was 34 years; 9% of men reported at least one would-not-recommend experience, which did not differ by sociodemographics, gender norm beliefs, or HIV stigma beliefs. The factors most strongly associated with would-not-recommend experiences were cost (aOR 5.8, 95%CI 2.9-11.4), cleanliness (aOR 4.2, 95%CI 1.8-9.9), medicine availability (aOR 3.3, 95%CI 1.7-6.4), and wait times (aOR 2.7, 95%CI 1.5-5.0). Reporting a would-not-recommend experience 12-24 months ago was associated with a 59% decrease in likelihood of testing for HIV in the last 12 months (aOR 0.41; 95% CI:0.17-0.96). Dissatisfaction with general health services was strongly associated with reduced HIV testing. Coverage of high-priority screening services like HIV testing may benefit from improving overall health system quality.

Strategies to improve antiretroviral therapy (ART) initiation and early engagement among men in sub-Saharan Africa: A scoping review of interventions in the era of universal treatment.

OBJECTIVES: Men in sub-Saharan Africa (SSA) have lower rates of antiretroviral therapy (ART) initiation and higher rates of early default than women. Little is known about effective interventions to improve men's outcomes. We conducted a scoping review of interventions aimed to increase ART initiation and/or early retention among men in SSA since universal treatment policies were implemented. METHODS: Three databases, HIV conference databases and grey literature were searched for studies published between January 2016 to May 2021 that reported on initiation and/or early retention among men. Eligibility criteria included: participants in SSA, data collected after universal treatment policies were implemented (2016-2021), quantitative data on ART initiation and/or early retention for males, general male population (not exclusively focused on key populations), intervention study (report outcomes for at least one non-standard service delivery strategy), and written in English. RESULTS: Of the 4351 sources retrieved, 15 (reporting on 16 interventions) met inclusion criteria. Of the 16 interventions, only two (2/16, 13%) exclusively focused on men. Five (5/16, 31%) were randomised control trials (RCT), one (1/16, 6%) was a retrospective cohort study, and 10 (10/16, 63%) did not have comparison groups. Thirteen (13/16, 81%) interventions measured ART initiation and six (6/16, 37%) measured early retention. Outcome definitions and time frames varied greatly, with seven (7/16, 44%) not specifying time frames at all. Five types of interventions were represented: optimising ART services at health facilities, community-based ART services, outreach support (such as reminders and facility escort), counselling and/or peer support, and conditional incentives. Across all intervention types, ART initiation rates ranged from 27% to 97% and early retention from 47% to 95%. CONCLUSIONS: Despite years of data of men's suboptimal ART outcomes, there is little high-quality evidence on interventions to increase men's ART initiation or early retention in SSA. Additional randomised or quasi-experimental studies are urgently needed.

Attrition from Care Among Men Initiating ART in Male-Only Clinics Compared with Men in General Primary Healthcare Clinics in Khayelitsha, South Africa: A Matched Propensity Score Analysis.

Men have higher rates of attrition from antiretroviral therapy (ART) programs than women. In Khayelitsha, a high HIV prevalence area in South Africa, two public sector primary healthcare clinics offer services, including HIV testing and treatment, exclusively to men. We compared attrition from ART care among men initiating ART at these clinics with male attrition in six general primary healthcare clinics in Khayelitsha. We described baseline characteristics of patients initiating ART at the male and general clinics from 1 January 2014 to 31 March 2018. We used exposure propensity scores (generated based on baseline health and age) to match male clinic patients 1:1 to males at other clinics. The association between attrition (death or loss to follow-up, defined as no visits for nine months) and clinic type was estimated using Cox proportional hazards regression. Follow-up time began at ART initiation and ended at attrition, clinic transfer, or dataset closure. Before matching, patients from male clinics (n = 784) were younger than males from general clinics (n = 2726), median age: 31.2 vs 35.5 years. Those initiating at male clinics had higher median CD4 counts at ART initiation [Male Clinic 1: 329 (IQR 210-431), Male Clinic 2: 364 (IQR 260-536), general clinics 258 (IQR 145-398), cells/mm3]. In the matched analysis (1451 person-years, 1568 patients) patients initiating ART at male clinics had lower attrition (HR 0.71; 95% CI 0.60-0.85). In separate analyses for each of the two male clinics, only the more established male clinic showed a protective effect. Male-only clinics reached younger, healthier men, and had lower ART attrition than general services. These findings support clinic-specific adaptations to create more male-friendly environments.

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.

Catastrophic costs among tuberculosis-affected households in Zimbabwe: A national health facility-based survey.

OBJECTIVES: To determine the incidence and major drivers of catastrophic costs among TB-affected households in Zimbabwe. METHODS: We conducted a nationally representative health facility-based survey with random cluster sampling among consecutively enrolled drug-susceptible (DS-TB) and drug-resistant TB (DR-TB) patients. Costs incurred and income lost due to TB illness were captured using an interviewer-administered standardised questionnaire. We used multivariable logistic regression to determine the risk factors for experiencing catastrophic costs. RESULTS: A total of 841 patients were enrolled and were weighted to 900 during data analysis. There were 500 (56%) males and 46 (6%) DR-TB patients. Thirty-five (72%) DR-TB patients were HIV co-infected. Overall, 80% (95% CI: 77-82) of TB patients and their households experienced catastrophic costs. The major cost driver pre-TB diagnosis was direct medical costs. Nutritional supplements were the major cost driver post-TB diagnosis, with a median cost of US$360 (IQR: 240-600). Post-TB median diagnosis costs were three times higher among DR-TB (US$1,659 [653-2,787]) than drug DS-TB-affected households (US$537 [204-1,134]). Income loss was five times higher among DR-TB than DS-TB patients. In multivariable analysis, household wealth was the only covariate that remained significantly associated with catastrophic costs: The poorest households had 16 times the odds of incurring catastrophic costs versus the wealthiest households (adjusted odds ratio [aOR: 15.7 95% CI: 7.5-33.1]). CONCLUSION: The majority of TB-affected households, especially those affected by DR-TB, experienced catastrophic costs. Since the major cost drivers fall outside the healthcare system, multi-sectoral approaches to TB control and linking TB patients to social protection may reduce catastrophic costs.

Patient Transfers and Their Impact on Gaps in Clinical Care: Differences by Gender in a Large Cohort of Adults Living with HIV on Antiretroviral Therapy in South Africa.

For people living with HIV (PLWH), patient transfers may affect engagement in care. We followed a cohort of PLWH in Cape Town, South Africa who tested positive for HIV in 2012-2013 from ART initiation in 2012-2016 through December 2016. Patient transfers were defined as moving from one healthcare facility to another on a different day, considering all healthcare visits and recorded HIV-visits only. We estimated incidence rates (IR) for transfers by time since ART initiation, overall and by gender, and associations between transfers and gaps of > 180 days in clinical care. Overall, 4,176 PLWH were followed for a median of 32 months, and 8% (HIV visits)-17% (all healthcare visits) of visits were patient transfers. Including all healthcare visits, transfers were highest through 3 months on ART (IR 20.2 transfers per 100 visits, 95% CI 19.2-21.2), but increased through 36 months on ART when only HIV visits were included (IR 9.7, 95% CI 8.8-10.8). Overall, women were more likely to transfer than men, and transfers were associated with gaps in care (IR ratio [IRR] 3.06 95% CI 2.83-3.32; HIV visits only). In this cohort, patient transfers were frequent, more common among women, and associated with gaps in care.

Estimating retention in HIV care accounting for clinic transfers using electronic medical records: evidence from a large antiretroviral treatment programme in the Western Cape, South Africa.

BACKGROUND: Estimates of retention in antiretroviral treatment (ART) programmes may be biased if patients who transfer to healthcare clinics are misclassified as lost to follow-up (LTFU) at their original clinic. In a large cohort, we estimated retention in care accounting for patient transfers using medical records. METHODS: Using linked electronic medical records, we followed adults living with HIV (PLWH) in Cape Town, South Africa from ART initiation (2012-2016) through database closure at 36 months or 30 June 2016, whichever came first. Retention was defined as alive and with a healthcare visit in the 180 days between database closure and administrative censoring on 31 December 2016. Participants who died or did not have a healthcare visit in > 180 days were censored at their last healthcare visit. We estimated the cumulative incidence of retention using Kaplan-Meier methods considering (i) only records from a participant's ART initiation clinic (not accounting for transfers) and (ii) all records (accounting for transfers), over time and by gender. We estimated risk differences and bootstrapped 95% confidence intervals to quantify misclassification in retention estimates due to patient transfers. RESULTS: We included 3406 PLWH initiating ART. Retention through 36 months on ART rose from 45.4% (95% CI 43.6%, 47.2%) to 54.3% (95% CI 52.4%, 56.1%) after accounting for patient transfers. Overall, 8.9% (95% CI 8.1%, 9.7%) of participants were misclassified as LTFU due to patient transfers. CONCLUSIONS: Patient transfers can appreciably bias estimates of retention in HIV care. Electronic medical records can help quantify patient transfers and improve retention estimates.

CONTEXTE: Les estimations de la rétention dans les programmes de traitement antirétroviral (ART) peuvent être biaisées si les patients qui sont transférés dans des cliniques de soins de santé sont classés à tort comme perdus au suivi (PS) dans leur clinique d'origine. Dans une large cohorte, nous avons estimé la rétention dans les soins en tenant compte des transferts de patients à l'aide des dossiers médicaux. MÉTHODES: A l'aide de dossiers médicaux électroniques reliés entre eux, nous avons suivi des adultes vivant avec le VIH (PVVIH) à Cape Town, en Afrique du Sud, depuis le début de l'ART (2012-2016) jusqu'à la clotûre de la base de données à 36 mois ou au 30 juin 2016, selon la première éventualité. La rétention a été définie comme étant en vie et avec une visite médicale dans les 180 jours entre la clôture de la base de données et recensement administrative le 31 décembre 2016. Les participants qui sont décédés ou qui n'ont pas eu de visite médicale dans un délai de plus de 180 jours ont été recensés lors de leur dernière visite médicale. Nous avons estimé l'incidence cumulative de la rétention en utilisant les méthodes de Kaplan-Meier en considérant: (i) uniquement les dossiers de la clinique d'initiation de l'ART d'un participant (sans tenir compte des transferts) et (ii) tous les dossiers (en tenant compte des transferts), au cours du temps et par sexe. Nous avons estimé les différences de risque et avons considéré des intervalles de confiance à 95% pour quantifier les erreurs de classification dans les estimations de rétention dues aux transferts de patients. RÉSULTAT: Nous avons inclus 3.406 PVVIH qui ont commencé un ART. La rétention sous ART est passée de 45,4% (IC 95%: 43,6-47,2) à 54,3% (IC 95%: 52,4-56,1) après avoir tenu compte des transferts de patients. Dans l'ensemble, 8,9% (IC 95%: 8,1-9,7) des participants ont été classés à tort dans la catégorie PS en raison des transferts de patients. CONCLUSIONS: Les transferts de patients peuvent biaiser sensiblement les estimations de la rétention dans les soins liés au VIH. Les dossiers médicaux électroniques peuvent aider à quantifier les transferts de patients et à améliorer les estimations de rétention.

Quantifying the HIV treatment cascade in a South African health sub-district by gender: retrospective cohort study.

OBJECTIVES: To quantify the HIV care cascade in a Cape Town sub-district to understand rates of linkage to and engagement in HIV care. METHODS: We used routinely collected data to reconstruct the treatment cascade for 8382 infected individuals who tested HIV + in 2012/2013. We obtained data on patient gender, year of initial HIV-positive test, age at testing and initial CD4 cell count and defined five stages of the HIV care cascade. We quantified attrition across cascade stages. RESULTS: Two-thirds of the sample (5646) were women. Men were older at time of first testing (36.5 vs. 31.3 years) and had more advanced HIV disease at diagnosis (298 vs. 404 CD4 cells/µL for women). The median duration of follow-up was 818 days. Among women, 90.5% attended an initial HIV care visit, 54.6% became eligible for antiretroviral therapy under local guidelines during follow-up, 49.3% initiated ART and 45.6% achieved a therapeutic response. Among men, 88.0% attended an initial HIV care visit, 67.4% became ART eligible during follow-up, 48.0% initiated ART and 42.4% achieved a therapeutic response. Approximately 3% of women and 5% of men died during follow-up. CONCLUSIONS: We were able to reconstruct the HIV treatment cascade using routinely collected data. In this setting, rates of engagement in care differ by gender in key stages of the cascade, with men faring worse than women at each cascade point. This highlights the need for interventions aimed at encouraging earlier testing, linkage, ART initiation and retention among men.

OBJECTIFS: Quantifier la cascade des soins du VIH dans un sous-district de Cape Town pour comprendre les taux de liaisons et d'engagement avec les soins du VIH. MÉTHODES: Nous avons utilisé des données collectées en routine pour reconstruire la cascade de traitement pour 8.382 personnes infectées, testées positives pour le VIH en 2012/13. Nous avons obtenu des données sur le sexe du patient, l'année du premier test positif pour le VIH, l'âge au moment de ce test et le nombre initial de cellules CD4, et avons défini cinq étapes de la cascade des soins du VIH. Nous avons quantifié l'attrition au long des étapes de la cascade. RÉSULTATS: Deux tiers de l'échantillon (5.646) étaient des femmes. Les hommes étaient plus âgés au moment du premier test (36,5 contre 31,3 ans) et avaient la maladie du VIH plus avancée au moment du diagnostic (298 contre 404 cellules CD4/µL pour les femmes). La durée médiane de suivi était de 818 jours. Parmi les femmes, 90,5% ont pris part à une première visite pour des soins du VIH, 54,6% sont devenues éligibles au traitement antirétroviral selon les directives locales au cours du suivi, 49,3% ont commencé une ART et 45,6% ont atteint une réponse thérapeutique. Chez les hommes, 88,0% ont pris part à une première visite pour les soins du VIH; 67,4% sont devenus éligibles à l'ART au cours du suivi, 48,0% ont commencé l'ART et 42,4% ont atteint une réponse thérapeutique. Environ 3% des femmes et 5% des hommes sont décédés au cours du suivi. CONCLUSIONS: Nous avons pu reconstruire la cascade de traitement du VIH en utilisant des données collectées en routine. Dans ce contexte, les taux d'engagement dans les soins diffèrent selon le sexe dans les étapes clés de la cascade, les hommes s'en tirant moins bien que les femmes à chaque point de la cascade. Cela met en évidence la nécessité d'interventions visant à encourager le dépistage précoce, la liaison, l'initiation de l'ART et la rétention chez les hommes.

The differential impact of HIV and antiretroviral therapy on gender-specific tuberculosis rates.

OBJECTIVE: To assess the impact of the HIV epidemic and the rollout of antiretroviral therapy (ART) from 2004 on the gender-specific TB burden in Cape Town, we investigated temporal changes in TB notification rates, the HIV-associated relative risk of TB and the population attributable risk fraction (PAF) of HIV by gender. METHODS: Annual TB notifications, mid-year population and HIV prevalence estimates were used to calculate rates per 100 000 population stratified by gender and HIV. Annual rate ratios (RR) of TB associated with HIV and PAF were calculated by gender. RESULTS: Pre-HIV TB notification rates were lower among women than men (146/100 000 vs. 247/100 000). With the onset of the HIV, epidemic rates increased 5.3-fold in women (to 778/100 000) and 3.7-fold in men (to 917/100 000) to a peak in 2008, after which they declined by 25% in women (to 634/100 000) and 18% in men (to 755/100 000) by 2014. The HIV-associated RR of TB was 25% higher in women than in men in 2006 (25 vs. 20), but decreased to the same level in 2014. HIV PAF declined between 2008 and 2014 from 56% to 50% and from 40% to 38% in women and men, respectively. CONCLUSIONS: The HIV epidemic led to greater relative increases in TB rates among women than men. The increased HIV-associated TB risk in women could be compatible with removal of the biological protection of female gender by HIV infection. The decline in RR and PAF in HIV-positive women could be explained by increasing ART usage reversing female gender-related susceptibility.

OBJECTIF: Afin d'évaluer l'impact de l'épidémie du VIH et le déploiement du traitement antirétroviral (ART depuis 2004) sur la charge de la tuberculose (TB) spécifique au sexe, à Cape Town, nous avons examiné les changements temporels dans les taux de notification de la TB, le risque relatif de TB associé au VIH et la fraction de risque attribuable à la population (FAP) du VIH par sexe. MÉTHODES: Les notifications annuelles de la TB, les estimations de la population en milieu d'année et de la prévalence du VIH ont été utilisées pour calculer les taux par 100.000 habitants stratifiés par sexe et VIH. Les rapports de risque (RR) annuels de TB associé au VIH et la FAP ont été calculés par sexe. RÉSULTATS: Les taux de notification de la TB avant le VIH étaient plus faibles chez les femmes que chez les hommes (146 sur 100.000 contre 247 sur 100.000). Avec le début de l'épidémie de VIH, les taux ont augmenté de 5,3 fois chez les femmes (à 778/100.000) et de 3,7 fois chez les hommes (à 917/100.000) pour atteindre un pic en 2008. Puis, ils ont diminué de 25% chez les femmes (à 634/100.000) et de 18% chez les hommes (à 755/100.000) en 2014. Les RR de TB associés au VIH étaient 25% plus élevés chez les femmes que chez les hommes en 2006 (25 contre 20), mais ont diminué au même niveau en 2014. La FAP du VIH a diminué entre 2008 et 2014, passant de 56% à 50% et de 40% à 38% chez les femmes et les hommes, respectivement. CONCLUSIONS: L'épidémie du VIH a entraîné une augmentation relative du taux de TB chez les femmes supérieure à celle des hommes. L'augmentation du risque de TB associé au VIH chez les femmes pourrait être compatible avec la suppression de la protection biologique du sexe féminin par l'infection au VIH. La baisse des RR et de la FAP chez les femmes VIH positives pourrait être expliquée par une augmentation de l'utilisation de l'ART inversant la sensibilité liée au sexe féminin.

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

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

Estimating the impact of antiretroviral treatment on adult mortality trends in South Africa: A mathematical modelling study.

BACKGROUND: Substantial reductions in adult mortality have been observed in South Africa since the mid-2000s, but there has been no formal evaluation of how much of this decline is attributable to the scale-up of antiretroviral treatment (ART), as previous models have not been calibrated to vital registration data. We developed a deterministic mathematical model to simulate the mortality trends that would have been expected in the absence of ART, and with earlier introduction of ART. METHODS AND FINDINGS: Model estimates of mortality rates in ART patients were obtained from the International Epidemiology Databases to Evaluate AIDS-Southern Africa (IeDEA-SA) collaboration. The model was calibrated to HIV prevalence data (1997-2013) and mortality data from the South African vital registration system (1997-2014), using a Bayesian approach. In the 1985-2014 period, 2.70 million adult HIV-related deaths occurred in South Africa. Adult HIV deaths peaked at 231,000 per annum in 2006 and declined to 95,000 in 2014, a reduction of 74.7% (95% CI: 73.3%-76.1%) compared to the scenario without ART. However, HIV mortality in 2014 was estimated to be 69% (95% CI: 46%-97%) higher in 2014 (161,000) if the model was calibrated only to HIV prevalence data. In the 2000-2014 period, the South African ART programme is estimated to have reduced the cumulative number of HIV deaths in adults by 1.72 million (95% CI: 1.58 million-1.84 million) and to have saved 6.15 million life years in adults (95% CI: 5.52 million-6.69 million). This compares with a potential saving of 8.80 million (95% CI: 7.90 million-9.59 million) life years that might have been achieved if South Africa had moved swiftly to implement WHO guidelines (2004-2013) and had achieved high levels of ART uptake in HIV-diagnosed individuals from 2004 onwards. The model is limited by its reliance on all-cause mortality data, given the lack of reliable cause-of-death reporting, and also does not allow for changes over time in tuberculosis control programmes and ART effectiveness. CONCLUSIONS: ART has had a dramatic impact on adult mortality in South Africa, but delays in the rollout of ART, especially in the early stages of the ART programme, have contributed to substantial loss of life. This is the first study to our knowledge to calibrate a model of ART impact to population-level recorded death data in Africa; models that are not calibrated to population-level death data may overestimate HIV-related mortality.

Do increasing rates of loss to follow-up in antiretroviral treatment programs imply deteriorating patient retention?

In several studies of antiretroviral treatment (ART) programs for persons with human immunodeficiency virus infection, investigators have reported that there has been a higher rate of loss to follow-up (LTFU) among patients initiating ART in recent years than among patients who initiated ART during earlier time periods. This finding is frequently interpreted as reflecting deterioration of patient retention in the face of increasing patient loads. However, in this paper we demonstrate by simulation that transient gaps in follow-up could lead to bias when standard survival analysis techniques are applied. We created a simulated cohort of patients with different dates of ART initiation. Rates of ART interruption, ART resumption, and mortality were assumed to remain constant over time, but when we applied a standard definition of LTFU, the simulated probability of being classified LTFU at a particular ART duration was substantially higher in recently enrolled cohorts. This suggests that much of the apparent trend towards increased LTFU may be attributed to bias caused by transient interruptions in care. Alternative statistical techniques need to be used when analyzing predictors of LTFU--for example, using "prospective" definitions of LTFU in place of "retrospective" definitions. Similar considerations may apply when analyzing predictors of LTFU from treatment programs for other chronic diseases.

Self-transfers, Hospital Admissions and Mortality Among Children and Adolescents Lost to Follow-up From Antiretroviral Therapy Programs in the Western Cape, South Africa Between 2004 and 2019: Linkage to Provincial Records.

BACKGROUND: Pediatric programs face a high rate of loss to follow-up (LTFU) among children and adolescents living with HIV (CAHIV). We assessed true outcomes and predictors of these among CAHIV who were LTFU using linkage to the Western Cape Provincial Health Data Centre at Western Cape sites of the International epidemiology Databases to Evaluate AIDS-Southern Africa collaboration. METHODS: We examined factors associated with self-transfer, hospital admission and mortality using competing risks regression in a retrospective cohort of CAHIV initiating antiretroviral therapy <15 years old between 2004 and 2019 and deemed LTFU (no recorded visit at the original facility for ≥180 days from the last visit date before database closure and not known to have officially transferred out or deceased). RESULTS: Of the 1720 CAHIV deemed LTFU, 802 (46.6%) had self-transferred and were receiving care elsewhere within the Western Cape, 463 (26.9%) had been hospitalized and 45 (2.6%) CAHIV had died. The overall rates of self-transfer, hospitalization, mortality and LTFU were 9.4 [95% confidence interval (CI): 8.8-10.1], 5.4 (95% CI: 5.0-6.0), 0.5 (95% CI: 0.4-0.7) and 4.8 (95% CI: 4.4-5.3) per 100 person-years respectively. Increasing duration on antiretroviral therapy before LTFU was associated with self-transfers while male sex, older age at last visit (≥10 years vs. younger) were associated with hospital admission and immune suppression at last visit was associated with 5 times higher mortality. CONCLUSIONS: Nearly half of CAHIV classified as LTFU had self-transferred to another health facility, a quarter had been hospitalized and a small proportion had died.

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.

ART history prior to conception: trends and association with postpartum disengagement from HIV care in Khayelitsha, South Africa (2013-2019): a retrospective cohort study.

INTRODUCTION: In recent years, the expansion of HIV treatment eligibility has resulted in an increase in people with antiretroviral therapy (ART) experience prior to pregnancy but little is known about postpartum engagement in care in this population. We examined differences in disengagement from HIV care after delivery by maternal ART history before conception. METHODS: We analysed data from people living with HIV (aged 15-49) in Khayelitsha, South Africa, with ≥1 live birth between April 2013 and March 2019. We described trends over time in ART history prior to estimated conception, classifying ART history groups as: (A) on ART with no disengagement (>270 days with no evidence of HIV care); (B) returned before pregnancy following disengagement; (C) restarted ART in pregnancy after disengagement; and (D) ART new start in pregnancy. We used Kaplan-Meier curves and proportional-hazards models (adjusted for maternal age, number of pregnancy records and year of delivery) to examine the time to disengagement from delivery to 2 years postpartum. RESULTS: Among 7309 pregnancies (in 6680 individuals), the proportion on ART (A) increased from 19% in 2013 to 41% in 2019. The proportions of those who returned (B) and restarted (C) increased from 2% to 13% and from 2% to 10%, respectively. There was a corresponding decline in the proportion of new starts (D) from 77% in 2013 to 36% in 2019. In the first recorded pregnancy per person in the study period, 26% (95% CI 25-27%) had disengaged from care by 1 year and 34% (95% CI 33-36%) by 2 years postpartum. Individuals who returned (B: aHR 2.10, 95% CI 1.70-2.60), restarted (C: aHR 3.32, 95% CI 2.70-4.09) and newly started ART (D: aHR 2.41, 95% CI 2.12-2.74) had increased hazards of postpartum disengagement compared to those on ART (A). CONCLUSIONS: There is a growing population of people with ART experience prior to conception and postpartum disengagement varies substantially by ART history. Antenatal care presents an important opportunity to understand prior ART experiences and an entry into interventions for strengthened engagement in HIV care.

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.