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.

Drivers of sex differences in the South African adult tuberculosis incidence and mortality trends, 1990-2019.

Males have higher tuberculosis incidence and mortality rates than females. This study aimed to assess how sex differences in tuberculosis incidence and mortality could be explained by sex differences in HIV, antiretroviral treatment (ART) uptake, smoking, alcohol abuse, undernutrition, diabetes, social contact rates, health-seeking patterns, and treatment discontinuation. We developed an age-sex-stratified dynamic tuberculosis transmission model and calibrated it to South African data. We estimated male-to-female (M:F) tuberculosis incidence and mortality ratios, the effect of the abovementioned factors on the M:F ratios and PAFs for the tuberculosis risk factors. Over the period 1990-2019, the M:F ratios for tuberculosis incidence and mortality rates persisted above 1.0, and the figures reached 1.70 and 1.65, respectively, by the end of 2019. In 2019, HIV contributed greater increases in tuberculosis incidence among females than males (54.5% vs. 45.6%); however, females experienced more reductions due to ART than males (38.3% vs. 17.5%). PAFs for tuberculosis incidence due to alcohol abuse, smoking, and undernutrition, in men were 51.4%, 29.5%, and 16.1%, respectively, higher than females (30.1%, 15.4%, and 10.7%, respectively); the PAF due to diabetes was higher in females than males (22.9% vs. 17.5%). Lower health-seeking rates in males accounted for a 7% higher mortality rate in men. The higher burden of tuberculosis in men highlights the need to improve men's access to routine screening and ensure earlier diagnosis. Sustained efforts in providing ART remain critical in reducing HIV-associated tuberculosis. Additional interventions to reduce alcohol abuse and tobacco smoking are also needed.

The impact of HIV and tuberculosis interventions on South African adult tuberculosis trends, 1990-2019: a mathematical modeling analysis.

OBJECTIVES: To quantify the South African adult tuberculosis (TB) incidence and mortality attributable to HIV between 1990 and 2019 and to estimate the reduction in TB incidence due to directly observed therapy, antiretroviral therapy (ART), isoniazid preventive therapy, increased TB screening, and Xpert MTB/RIF. METHODS: We developed a dynamic TB transmission model for South Africa. A Bayesian approach was used to calibrate the model to South African-specific data sources. Counterfactual scenarios were simulated to estimate TB incidence and mortality attributable to HIV and the impact of interventions on TB incidence. RESULTS: Between 1990 and 2019, 8.8 million (95% confidence interval [CI] 8.3-9.3 million) individuals developed TB, and 2.1 million (95% CI 2.0-2.2 million) died from TB. A total of 55% and 69% of TB cases and mortality were due to HIV, respectively. Overall, TB screening and ART substantially reduced TB incidence by 28.2% (95% CI 26.4-29.8%) and 20.0% (95% CI 19.2-20.7%), respectively, in 2019; other interventions had minor impacts. CONCLUSION: HIV has dramatically increased TB incidence and mortality in South Africa. The provision of ART and intensification of TB screening explained most recent declines in TB incidence.

Challenges in estimating HIV prevalence trends and geographical variation in HIV prevalence using antenatal data: Insights from mathematical modelling.

BACKGROUND: HIV prevalence data among pregnant women have been critical to estimating HIV trends and geographical patterns of HIV in many African countries. Although antenatal HIV prevalence data are known to be biased representations of HIV prevalence in the general population, mathematical models have made various adjustments to control for known sources of bias, including the effect of HIV on fertility, the age profile of pregnant women and sexual experience. METHODS AND FINDINGS: We assessed whether assumptions about antenatal bias affect conclusions about trends and geographical variation in HIV prevalence, using simulated datasets generated by an agent-based model of HIV and fertility in South Africa. Results suggest that even when controlling for age and other previously-considered sources of bias, antenatal bias in South Africa has not been constant over time, and trends in bias differ substantially by age. Differences in the average duration of infection explain much of this variation. We propose an HIV duration-adjusted measure of antenatal bias that is more stable, which yields higher estimates of HIV incidence in recent years and at older ages. Simpler measures of antenatal bias, which are not age-adjusted, yield estimates of HIV prevalence and incidence that are too high in the early stages of the HIV epidemic, and that are less precise. Antenatal bias in South Africa is substantially greater in urban areas than in rural areas. CONCLUSIONS: Age-standardized approaches to defining antenatal bias are likely to improve precision in model-based estimates, and further recency adjustments increase estimates of HIV incidence in recent years and at older ages. Incompletely adjusting for changing antenatal bias may explain why previous model estimates overstated the early HIV burden in South Africa. New assays to estimate the fraction of HIV-positive pregnant women who are recently infected could play an important role in better estimating antenatal bias.

Tuberculosis, Human Immunodeficiency Virus, and the Association With Transient Hyperglycemia in Periurban South Africa.

BACKGROUND: Diabetes mellitus (DM) increases tuberculosis (TB) risk. We assessed the prevalence of hyperglycemia (DM and impaired glucose regulation [IGR]) in persons with TB and the association between hyperglycemia and TB at enrollment and 3 months after TB treatment in the context of human immunodeficiency virus (HIV) infection. METHODS: Adults presenting at a Cape Town TB clinic were enrolled. TB cases were defined by South African guidelines, while non-TB participants were those who presented with respiratory symptoms, negative TB tests, and resolution of symptoms 3 months later without TB treatment. HIV status was ascertained through medical records or HIV testing. All participants were screened for DM using glycated hemoglobin and fasting plasma glucose at TB treatment and after 3 months. The association between TB and DM was assessed. RESULTS: Overall DM prevalence was 11.9% (95% confidence interval [CI], 9.1%-15.4%) at enrollment and 9.3% (95% CI, 6.4%-13%) at follow-up; IGR prevalence was 46.9% (95% CI, 42.2%-51.8%) and 21.5% (95% CI, 16.9%-26.3%) at enrollment and follow-up. TB/DM association was significant at enrollment (odds ratio [OR], 2.41 [95% CI, 1.3-4.3]) and follow-up (OR, 3.3 [95% CI, 1.5-7.3]), whereas TB/IGR association was only positive at enrollment (OR, 2.3 [95% CI, 1.6-3.3]). The TB/DM association was significant at enrollment in both new and preexisting DM, but only persisted at follow-up in preexisting DM in patients with HIV-1 infection. CONCLUSIONS: Our study demonstrated high prevalence of transient hyperglycemia and a significant TB/DM and TB/IGR association at enrollment in newly diagnosed DM, but persistent hyperglycemia and TB/DM association in patients with HIV-1 infection and preexisting DM, despite TB therapy.

Trilateral overlap of tuberculosis, diabetes and HIV-1 in a high-burden African setting: implications for TB control.

The diabetes mellitus burden is growing in countries where tuberculosis (TB) and HIV-1 remain major challenges, threatening TB control efforts. This study determined the association between TB and diabetes/impaired glucose regulation in the context of HIV-1.A cross-sectional study was conducted at a TB clinic in Cape Town (South Africa). Participants were screened for diabetes and impaired glucose regulation using fasting plasma glucose, oral glucose tolerance test and glycated haemoglobin (HbA1c).414 TB and 438 non-TB participants were enrolled. In multivariable analysis, diabetes was associated with TB (OR 2.4, 95% CI 1.3-4.3; p=0.005), with 14% population-attributable risk fraction; however, this association varied by diagnostic test (driven by HbA1c). The association remained significant in HIV-1-infected individuals (OR 2.4, 95% CI 1.1-5.2; p=0.030). A high prevalence of impaired glucose regulation (65.2% among TB cases) and a significant association with TB (OR 2.3, 95% CI 1.6-3.3; p<0.001) was also found.Diabetes and impaired glucose regulation prevalence was high and associated with TB, particularly in HIV-1-infected individuals, highlighting the importance of diabetes screening. The variation in findings by diagnostic test highlights the need for better glycaemia markers to inform screening in the context of TB and HIV-1.