Yann Ruffieux

Background: Recurrent self-harm is common and is associated with an increased risk of unnatural death including suicide and fatal accidents. We developed and validated prognostic models to stratify individuals by risk of unnatural death after healthcare presentation for non-fatal self-harm to support clinical decision-making and targeted prevention when capacity to deliver evidence-based intervention is limited. Methods: We used insurance claims and vital registration data from 6846 South African medical insurance beneficiaries aged ≥10 years who were discharged alive after healthcare presentation for self-harm during 2011–2021 to develop and validate models predicting unnatural death after non-fatal self-harm. We fitted competing-risk regression models to predict unnatural death within 1–3 years after presentation and discharge. Variable selection was guided by the least absolute shrinkage and selection operator. We used bootstrapping for internal validation and estimated optimism-corrected concordance indices (C-index), calibration intercepts and slopes, and for risk stratification the proportions of unnatural deaths captured across predicted-risk groups. Final models included age, sex, encounter characteristics, prior psychotropic medication use and selected prior mental disorder diagnoses. Results: The final models achieved optimism-corrected C-indices of 0.74 at presentation and 0.75–0.76 at discharge and identified 86–88% of observed unnatural deaths within 2 years among the 40% of individuals with the highest predicted risk. Models showed little evidence of systematic miscalibration (optimism-corrected calibration intercepts −0.02 to −0.01), but some overfitting (optimism-corrected calibration slopes 0.84–0.92). Using the model with the highest optimism-corrected C-index, the simplified discharge model, the observed 2-year risk of unnatural death was 0.15% (95% CI 0.06% to 0.32%) among the 60% of individuals with the lowest predicted risk, comparable to the risk among 1 249 760 individuals without a self-harm history (0.14%, (95% CI 0.14% to 0.15%)). Conclusions: The prediction models effectively rank individuals accessing private sector care in South Africa by their probability of unnatural death following healthcare presentation for non-fatal self-harm. Clinical implications: The models are intended to support clinical decision-making and guide the prioritisation of individuals with predicted high risk for targeted interventions, supporting more efficient allocation of mental health care capacity, which is often limited in low- and middle-income settings.

Background: Human immunodeficiency virus (HIV) increases the risk of developing cancer. We aimed to assign HIV status to cancers diagnosed in public laboratories recorded in the National Cancer Registry (NCR) in South Africa, guided by HIV counselling and testing guidelines. Methods: We used natural language processing to extract HIV‐related information from free‐text reports and probabilistic record linkage to match cancers diagnosed between 2004 and 2021 to HIV‐related tests from the National Health Laboratory Service Corporate Data Warehouse. We assigned HIV status based on the results of the HIV‐related tests and their timing relative to cancer diagnosis. We used descriptive statistics and logistic regression to examine HIV status documentation patterns and HIV prevalence in cancer patients. Results: Of the 496,517 cancers reported to the NCR, 41% ( n = 203,937) had a documented HIV status. Documentation increased from 29% in 2004–2009 to 52% in 2016–2021. The odds of having a documented HIV status were 20% higher in females than in males and 16%–28% lower in other population groups compared with Black Africans. Patients with infection‐related cancers had almost threefold higher odds of having a documented HIV status than patients with infection‐unrelated cancers. Among cancer patients with documented HIV status, HIV prevalence was 75% for infection‐related and 32% for infection‐unrelated cancers. Conclusion: HIV status documentation among people with cancer has improved over time, but it is still suboptimal. Clinicians and pathologists in HIV endemic areas need to improve HIV ascertainment at cancer diagnosis and reporting to cancer registries to inform patient care and guide cancer control efforts.

Background: Women with human immunodeficiency virus-1 (HIV) (WWH) have a higher cervical cancer risk than women without HIV. The timing and extent to which HIV viremia and immunodeficiency contribute to cervical carcinogenesis remain incompletely understood. Methods: We conducted a cohort study using medical claims data from a South African HIV program (2011–2022) and calculated incidence rates of cervical precancer and cancer. Cox proportional hazards models assessed associations with CD4 cell count and HIV ribonucleic acid (RNA). We tested summary and point-in-time CD4 and HIV RNA measures with 6–36 months lag periods. Models were adjusted for age, calendar year, and antiretroviral therapy (ART) initiation; fully adjusted models included both CD4 count and HIV RNA. Results: Over 66 000 WWH contributed more than 300 000 person-years; 1202 WWH developed moderate dysplasia (incidence rate: 394/100 000 person-years), 1237 severe dysplasia (405/100 000 person-years), 211 carcinoma in situ (66/100 000 person-years), and 257 cervical cancer (70/100 000 person-years). Lower CD4 counts were strongly associated with higher rates of cervical dysplasia, carcinoma in situ, and cancer, independent of HIV RNA. Lowest CD4 count over 30 months was the most informative measure for cervical dysplasia while CD4 count lagged by 24 months was most informative for cervical cancer. Higher HIV RNA was associated with increased risk of precancer and cancer in models unadjusted for CD4 count, with associations attenuated after adjustment. Conclusions: Maintaining high CD4 counts and achieving viral suppression through early ART initiation, along with using CD4 cell count for risk stratification in cervical screening, may help improve cervical cancer prevention among WWH in South Africa.

Objectives: To assess the association of HIV and overall survival among medically insured head and neck cancer (HNC) patients in South Africa and to examine factors associated with the type of treatment received. Methods: We used reimbursement claims data from a South African medical insurance scheme database from 1 January 2011 to 1 July 2020. We included individuals with at least two International Classification of Diseases (ICD‐10) codes for HNC and at least one cancer treatment code within 180 days of the HNC diagnosis. We used logistic regression to identify factors associated with receiving a specific type of cancer treatment and Cox proportional hazards models to examine factors associated with all‐cause mortality. Results: We included 566 HNC patients, 49 of whom lived with HIV and 383 were male. Patients with HIV were substantially younger at HNC diagnosis (median age: 52.5 years) than patients without HIV (median age: 61.6 years). We found no clear association between HIV status and the treatment type received. The median survival was 3.78 years (95% confidence interval [CI] 3.01–6.08) and the five‐year survival was 46.0% (95% CI 41.2%–51.5%). The risk of death was higher among patients with HIV than those without HIV (adjusted hazard ratio 1.68; 95% CI 1.00–2.81). Conclusion: Medically insured HNC patients in South Africa with HIV had higher mortality than those without HIV. This underscores the importance of tailored cancer care strategies for HNC patients with HIV.

Among 130 992 people with HIV (PWH) in South Africa, 60 anal cancers were diagnosed. Lower CD4 counts and, to a lesser extent, higher HIV RNA viral loads were associated with an increased anal cancer risk. Maintaining high CD4 counts may contribute to anal cancer prevention among PWH in South Africa.

Background: Self-harm is a major public health concern globally and in South Africa. Individuals with a history of self-harm are at increased risk of unnatural death, including suicide and fatal accidents. This study investigates the incidence and predictors of self-harm and its role as a predictor for subsequent unnatural death. Methods and findings: We conducted a cohort study using insurance claims and vital registration data from beneficiaries of South African medical insurance schemes (2011–2022), aged 10 years or older. We estimated the cause-specific cumulative incidences of healthcare encounters for intentional self-harm (International Classification of Diseases 10th Revision [ICD-10] codes X60-X84) and unnatural deaths (ICD-10 codes V01-Y98), using the Aalen–Johansen method. We assessed predictors of both outcomes using Cox regression. We followed 1,356,119 beneficiaries (median age 33 years, 52.2% female) for a median of 3 years, during which 7,510 (0.6%) had a healthcare encounter for self-harm. The 5-year cumulative incidence of self-harm ranged from 0.2% in males aged 10–14 to 2.1% in females aged 15–24. Sex, age, and mental disorders were strong predictors for self-harm, while HIV was a modest predictor. Among individuals who survived a self-harm event, the five-year cumulative incidence of subsequent unnatural death was 3.43% (95% CI [2.38, 4.76]) for males and 0.77% (95% CI [0.48, 1.19]) for females. Non-fatal self-harm was a strong predictor of subsequent unnatural death in both males (hazard ratio [HR] 7.03, 95% CI [5.27, 9.39]) and females (HR 4.63, 95% CI [3.00, 7.15]). The study’s main limitations include potential under-ascertainment of self-harm incidence due to reliance on routine data, and the unavailability of the exact cause of death, preventing analysis of suicide. Conclusion: Self-harm is common among beneficiaries of South African private medical insurance, with the highest risk in young females and individuals with mental disorders. These groups may benefit from targeted screening and early intervention. Non-fatal self-harm was a strong predictor of subsequent unnatural death, underscoring the need for suicide-specific brief interventions for individuals presenting with self-harm.

Background: More than 7.5 million people in South Africa have HIV, but little is known about the association of HIV and anal cancer incidence. We examined anal cancer incidence in a large South African cohort of insured men and women. Methods: We conducted a cohort study using reimbursement claims data from a South African medical insurance scheme (01/2011-07/2020) to assess anal cancer rates among people with and without HIV aged ≥18 years. We estimated adjusted hazard ratios (aHRs) for the association of HIV and incident anal cancer using flexible parametric survival models. Covariates included sex, age, calendar year, a history of genital warts and other sexually transmitted infections, and in women, cervical precancer. Results: We included 1 068 915 people of whom 69 985 (7%) were living with HIV. Over 3 933 145 person-years, 122 anal cancers were diagnosed (crude rate: 3.1/100 000 person-years; 95% confidence intervals [CI] 2.6–3.7). People with HIV had a 4-fold higher anal cancer risk than people without HIV (aHR 4.43; 95% CI 2.44–8.04). While anal cancer rates were similar among men and women, older age (≥65 vs 45–54 years; aHR 5.01; 95% CI: 2.94–8.53), a history of genital warts (aHR 7.56; 95% CI: 2.28–25.07), and among women, a prior cervical precancer diagnosis (aHR 5.70; 95% CI 1.75–18.58) were associated with a higher anal cancer risk. Conclusions: In South Africa, men and women with HIV, older individuals, people with a history of genital warts, and women with a prior cervical precancer diagnosis might benefit from prioritized access to anal cancer screening.

Introduction: People with HIV (PWH) have a high burden of mental health disorders, which contribute to increased mortality due to elevated rates of physical illness, suicide or fatal accidents. Additionally, mental health disorders can adversely affect antiretroviral therapy (ART) adherence, leading to increased HIV‐related mortality. This study aims to quantify the difference in mortality between PWH who have a mental health disorder and PWH without mental health disorders in South Africa (SA) and North America (NA). Methods: This cohort study includes PWH aged 18 years or older who initiated ART between 2000 and 2021 at a national private‐sector HIV programme in SA and 13 programmes in the United States and Canada. Mental health disorders were diagnosed according to ICD‐10 codes F10‐F99, which include psychotic disorders, bipolar disorders, depression, anxiety and substance use disorders. We estimated life‐years lost (LYL) associated with mental health disorders, quantifying the average difference in remaining life expectancy between individuals diagnosed with a mental health disorder and those without such diagnoses. Results: The study included 119,785 participants from SA (57.4% female, median age 39 years) and 142,044 from NA (85.0% male, median age 43 years). In SA, 57,999 (48.4%) were diagnosed with a mental health disorder, compared with 93,518 (65.8%) in NA. In SA, the LYL associated with any mental health disorder were 3.42 years (95% CI 2.42−4.28) in males and 2.95 years (0.67−5.95) in females. Corresponding figures for NA were 4.16 years (3.71−4.59) in males and 4.64 years (2.93−6.05) in females. In both regions, LYL were higher for psychotic and substance use disorders than for depression and anxiety. Losses were primarily due to natural deaths at CD4 counts ≥200 cells/µl, with considerable contributions at CD4 counts <200 cells/µl. Unnatural causes also contributed to the loss of life‐years in males from SA and males and females from NA. Conclusions: PWH affected by mental health disorders experience higher mortality, primarily from natural causes. LYL were associated with both immunosuppression and higher CD4 levels. Improved management of HIV and physical comorbidities among PWH affected by mental health disorders may enhance their prognosis.

Background: Most research on human immunodeficiency virus-1 (HIV-1) viremia and cancer risk is from high-income countries. We evaluated the association between HIV-1 viremia and the risk of various cancer types among people with HIV (PWH) in South Africa. Methods: We analyzed data from the South African HIV Cancer Match study, based on laboratory measurements from the National Health Laboratory Service and cancer records from the National Cancer Registry from 2004 to 2014. Using Cox proportional hazards models, we estimated hazard ratios (HR) for cancer incidence per unit increase in time-updated Log10 HIV-1 RNA viral load copies/mL. We created partially adjusted (sex, age, calendar year) and fully adjusted models (additionally including time-updated CD4 count). Results: We included 2 770 200 PWH with 10 175 incident cancers; most common were cervical cancer (N = 2481), Kaposi sarcoma (N = 1902), breast cancer (N = 1063), and non-Hodgkin lymphoma (N = 863). Hazard ratios for the association of HIV-1 viremia and cancer risk changed after partial and full adjustment and were generally attenuated for infection-related cancers but tended to increase for infection-unrelated cancers. In the fully adjusted model, HIV-1 viremia was associated with an increased risk of Kaposi sarcoma (HR per unit increase in Log10 HIV-1 RNA viral load: 1.38; 95% confidence interval [CI], 1.35–1.42), leukemia (HR: 1.28; 95% CI, 1.13–1.45), non-Hodgkin lymphoma (HR: 1.24; 95% CI, 1.19–1.29), conjunctival cancer (HR: 1.19; 95% CI, 1.11–1.25), and colorectal cancer (HR: 1.11; 95% CI, 1.02–1.21). Associations with other cancer types were weaker or absent. Conclusions: Our findings underline the importance of sustained viral suppression for cancer prevention among PWH in South Africa.