From conceptualising to modelling structural determinants and interventions in HIV transmission dynamics models: a scoping review and methodological framework for evidence-based analyses.

BACKGROUND: Including structural determinants (e.g. criminalisation, stigma, inequitable gender norms) in dynamic HIV transmission models is important to help quantify their population-level impacts and guide implementation of effective interventions that reduce the burden of HIV and inequalities thereof. However, evidence-based modelling of structural determinants is challenging partly due to a limited understanding of their causal pathways and few empirical estimates of their effects on HIV acquisition and transmission. METHODS: We conducted a scoping review of dynamic HIV transmission modelling studies that evaluated the impacts of structural determinants, published up to August 28, 2023, using Ovid Embase and Medline online databases. We appraised studies on how models represented exposure to structural determinants and causal pathways. Building on this, we developed a new methodological framework and recommendations to support the incorporation of structural determinants in transmission dynamics models and their analyses. We discuss the data and analyses that could strengthen the evidence used to inform these models. RESULTS: We identified 17 HIV modelling studies that represented structural determinants and/or interventions, including incarceration of people who inject drugs (number of studies [n] = 5), violence against women (n = 3), HIV stigma (n = 1), and housing instability (n = 1), among others (n = 7). Most studies (n = 10) modelled exposures dynamically. Almost half (8/17 studies) represented multiple exposure histories (e.g. current, recent, non-recent exposure). Structural determinants were often assumed to influence HIV indirectly by influencing mediators such as contact patterns, condom use, and antiretroviral therapy use. However, causal pathways' assumptions were sometimes simple, with few mediators explicitly represented in the model, and largely based on cross-sectional associations. Although most studies calibrated models using HIV epidemiological data, less than half (7/17) also fitted or cross-validated to data on the prevalence, frequency, or effects of exposure to structural determinants. CONCLUSIONS: Mathematical models can play a crucial role in elucidating the population-level impacts of structural determinants and interventions on HIV. We recommend the next generation of models reflect exposure to structural determinants dynamically and mechanistically, and reproduce the key causal pathways, based on longitudinal evidence of links between structural determinants, mediators, and HIV. This would improve the validity and usefulness of predictions of the impacts of structural determinants and interventions.

Population size, HIV prevalence, and antiretroviral therapy coverage among key populations in sub-Saharan Africa: collation and synthesis of survey data, 2010-23.

BACKGROUND: Key population HIV programmes in sub-Saharan Africa require epidemiological information to ensure equitable and universal access to effective services. We aimed to consolidate and harmonise survey data among female sex workers, men who have sex with men, people who inject drugs, and transgender people to estimate key population size, HIV prevalence, and antiretroviral therapy (ART) coverage for countries in mainland sub-Saharan Africa. METHODS: Key population size estimates, HIV prevalence, and ART coverage data from 39 sub-Saharan Africa countries between 2010 and 2023 were collated from existing databases and verified against source documents. We used Bayesian mixed-effects spatial regression to model urban key population size estimates as a proportion of the gender-matched, year-matched, and area-matched population aged 15-49 years. We modelled subnational key population HIV prevalence and ART coverage with age-matched, gender-matched, year-matched, and province-matched total population estimates as predictors. FINDINGS: We extracted 2065 key population size data points, 1183 HIV prevalence data points, and 259 ART coverage data points. Across national urban populations, a median of 1·65% (IQR 1·35-1·91) of adult cisgender women were female sex workers, 0·89% (0·77-0·95) were men who have sex with men, 0·32% (0·31-0·34) were men who injected drugs, and 0·10% (0·06-0·12) were women who were transgender. HIV prevalence among key populations was, on average, four to six times higher than matched total population prevalence, and ART coverage was correlated with, but lower than, the total population ART coverage with wide heterogeneity in relative ART coverage across studies. Across sub-Saharan Africa, key populations were estimated as comprising 1·2% (95% credible interval 0·9-1·6) of the total population aged 15-49 years but 6·1% (4·5-8·2) of people living with HIV. INTERPRETATION: Key populations in sub-Saharan Africa experience higher HIV prevalence and lower ART coverage, underscoring the need for focused prevention and treatment services. In 2024, limited data availability and heterogeneity constrain precise estimates for programming and monitoring trends. Strengthening key population surveys and routine data within national HIV strategic information systems would support more precise estimates. FUNDING: UNAIDS, Bill & Melinda Gates Foundation, and US National Institutes of Health.

Comparison of Empirically Derived and Model-Based Estimates of Key Population HIV Incidence and the Distribution of New Infections by Population Group in Sub-Saharan Africa.

BACKGROUND: The distribution of new HIV infections among key populations, including female sex workers (FSWs), gay men and other men who have sex with men (MSM), and people who inject drugs (PWID) are essential information to guide an HIV response, but data are limited in sub-Saharan Africa (SSA). We analyzed empirically derived and mathematical model-based estimates of HIV incidence among key populations and compared with the Joint United Nations Programme on HIV/AIDS (UNAIDS) estimates. METHODS: We estimated HIV incidence among FSW and MSM in SSA by combining meta-analyses of empirical key population HIV incidence relative to the total population incidence with key population size estimates (KPSE) and HIV prevalence. Dynamic HIV transmission model estimates of HIV incidence and percentage of new infections among key populations were extracted from 94 country applications of 9 mathematical models. We compared these with UNAIDS-reported distribution of new infections, implied key population HIV incidence and incidence-to-prevalence ratios. RESULTS: Across SSA, empirical FSW HIV incidence was 8.6-fold (95% confidence interval: 5.7 to 12.9) higher than total population female 15-39 year incidence, and MSM HIV incidence was 41.8-fold (95% confidence interval: 21.9 to 79.6) male 15-29 year incidence. Combined with KPSE, these implied 12% of new HIV infections in 2021 were among FSW and MSM (5% and 7% respectively). In sensitivity analysis varying KPSE proportions within 95% uncertainty range, the proportion of new infections among FSW and MSM was between 9% and 19%. Insufficient data were available to estimate PWID incidence rate ratios. Across 94 models, median proportion of new infections among FSW, MSM, and PWID was 6.4% (interquartile range 3.2%-11.7%), both much lower than the 25% reported by UNAIDS. CONCLUSION: Empirically derived and model-based estimates of HIV incidence confirm dramatically higher HIV risk among key populations in SSA. Estimated proportions of new infections among key populations in 2021 were sensitive to population size assumptions and were substantially lower than estimates reported by UNAIDS.

Measuring HIV Acquisitions Among Partners of Key Populations: Estimates From HIV Transmission Dynamic Models.

BACKGROUND: Key populations (KPs), including female sex workers (FSWs), gay men and other men who have sex with men (MSM), people who inject drugs (PWID), and transgender women (TGW) experience disproportionate risks of HIV acquisition. The UNAIDS Global AIDS 2022 Update reported that one-quarter of all new HIV infections occurred among their non-KP sexual partners. However, this fraction relied on heuristics regarding the ratio of new infections that KPs transmitted to their non-KP partners to the new infections acquired among KPs (herein referred to as "infection ratios"). We recalculated these ratios using dynamic transmission models. SETTING: One hundred seventy-eight settings (106 countries). METHODS: Infection ratios for FSW, MSM, PWID, TGW, and clients of FSW were estimated from 12 models for 2020. RESULTS: Median model estimates of infection ratios were 0.7 (interquartile range: 0.5-1.0; n = 172 estimates) and 1.2 (0.8-1.8; n = 127) for acquisitions from FSW clients and transmissions from FSW to all their non-KP partners, respectively, which were comparable with the previous UNAIDS assumptions (0.2-1.5 across regions). Model estimates for female partners of MSM were 0.5 (0.2-0.8; n = 20) and 0.3 (0.2-0.4; n = 10) for partners of PWID across settings in Eastern and Southern Africa, lower than the corresponding UNAIDS assumptions (0.9 and 0.8, respectively). The few available model estimates for TGW were higher [5.1 (1.2-7.0; n = 8)] than the UNAIDS assumptions (0.1-0.3). Model estimates for non-FSW partners of FSW clients in Western and Central Africa were high (1.7; 1.0-2.3; n = 29). CONCLUSIONS: Ratios of new infections among non-KP partners relative to KP were high, confirming the importance of better addressing prevention and treatment needs among KP as central to reducing overall HIV incidence.

Trends in HIV testing, the treatment cascade, and HIV incidence among men who have sex with men in Africa: a systematic review and meta-analysis.

BACKGROUND: Gay, bisexual, and other men who have sex with men (MSM) are disproportionately affected by HIV. In Africa, MSM face structural barriers to HIV prevention and treatment that increase their vulnerability to HIV acquisition and transmission, and undermine the HIV response. In this systematic review, we aimed to explore progress towards increases in HIV testing, improving engagement in the HIV treatment cascade, and HIV incidence reductions among MSM in Africa. METHODS: We searched Embase, MEDLINE, Global Health, Scopus, and Web of Science for cross-sectional and longitudinal studies reporting HIV testing, knowledge of status, care, antiretroviral therapy (ART) use, viral suppression, and HIV incidence among MSM in Africa published between Jan 1, 1980, and March 3, 2023. We pooled surveys using Bayesian generalised linear mixed-effects models, used meta-regression to assess time trends, and compared HIV incidence estimates among MSM with those of all men. FINDINGS: Of 9278 articles identified, we included 152 unique studies published in 2005-23. In 2020, we estimate that 73% (95% credible interval [CrI] 62-87) of MSM had ever tested for HIV. HIV testing in the past 12 months increased over time in central, western, eastern, and southern Africa (odds ratio per year [ORyear] 1·23, 95% CrI 1·01-1·51, n=46) and in 2020 an estimated 82% (70-91) had tested in the past 12 months, but only 51% (30-72) of MSM living with HIV knew their HIV status. Current ART use increased over time in central and western (ORyear 1·41, 1·08-1·93, n=9) and eastern and southern Africa (ORyear 1·37, 1·04-1·84, n=17). We estimated that, in 2020, 73% (47-88) of all MSM living with HIV in Africa were currently on ART. Nevertheless, we did not find strong evidence to suggest that viral suppression increased, with only 69% (38-89) of MSM living with HIV estimated to be virally suppressed in 2020. We found insufficient evidence of a decrease in HIV incidence over time (incidence ratio per year 0·96, 95% CrI 0·63-1·50, n=39), and HIV incidence remained high in 2020 (6·9 per 100 person-years, 95% CrI 3·1-27·6) and substantially higher (27-199 times higher) than among all men. INTERPRETATION: HIV incidence remains high, and might not be decreasing among MSM in Africa over time, despite some increases in HIV testing and ART use. Achieving the UNAIDS 95-95-95 targets for diagnosis, treatment, and viral suppression equitably for all requires renewed focus on this key population. Combination interventions for MSM are urgently required to reduce disparities in HIV incidence and tackle the social, structural, and behavioural factors that make MSM vulnerable to HIV acquisition. FUNDING: US National Institutes of Health, UK Medical Research Council, Canadian Institutes of Health Research, and Fonds de Recherche du Québec-Santé. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Population sizes, HIV prevalence, and HIV prevention among men who paid for sex in sub-Saharan Africa (2000-2020): A meta-analysis of 87 population-based surveys.

BACKGROUND: Key populations, including sex workers, are at high risk of HIV acquisition and transmission. Men who pay for sex can contribute to HIV transmission through sexual relationships with both sex workers and their other partners. To characterize the population of men who pay for sex in sub-Saharan Africa (SSA), we analyzed population size, HIV prevalence, and use of HIV prevention and treatment. METHODS AND FINDINGS: We performed random-effects meta-analyses of population-based surveys conducted in SSA from 2000 to 2020 with information on paid sex by men. We extracted population size, lifetime number of sexual partners, condom use, HIV prevalence, HIV testing, antiretroviral (ARV) use, and viral load suppression (VLS) among sexually active men. We pooled by regions and time periods, and assessed time trends using meta-regressions. We included 87 surveys, totaling over 368,000 male respondents (15-54 years old), from 35 countries representing 95% of men in SSA. Eight percent (95% CI 6%-10%; number of surveys [Ns] = 87) of sexually active men reported ever paying for sex. Condom use at last paid sex increased over time and was 68% (95% CI 64%-71%; Ns = 61) in surveys conducted from 2010 onwards. Men who paid for sex had higher HIV prevalence (prevalence ratio [PR] = 1.50; 95% CI 1.31-1.72; Ns = 52) and were more likely to have ever tested for HIV (PR = 1.14; 95% CI 1.06-1.24; Ns = 81) than men who had not paid for sex. Men living with HIV who paid for sex had similar levels of lifetime HIV testing (PR = 0.96; 95% CI 0.88-1.05; Ns = 18), ARV use (PR = 1.01; 95% CI 0.86-1.18; Ns = 8), and VLS (PR = 1.00; 95% CI 0.86-1.17; Ns = 9) as those living with HIV who did not pay for sex. Study limitations include a reliance on self-report of sensitive behaviors and the small number of surveys with information on ARV use and VLS. CONCLUSIONS: Paying for sex is prevalent, and men who ever paid for sex were 50% more likely to be living with HIV compared to other men in these 35 countries. Further prevention efforts are needed for this vulnerable population, including improved access to HIV testing and condom use initiatives. Men who pay for sex should be recognized as a priority population for HIV prevention.

What Is the Burden of Heterosexually Acquired HIV Due to HSV-2? Global and Regional Model-Based Estimates of the Proportion and Number of HIV Infections Attributable to HSV-2 Infection.

BACKGROUND: Biological and epidemiological evidence suggest that herpes simplex virus type 2 (HSV-2) elevates HIV acquisition and transmission risks. We improved previous estimates of the contribution of HSV-2 to HIV infections by using a dynamic transmission model. SETTING: World Health Organization regions. METHODS: We developed a mathematical model of HSV-2/HIV transmission among 15- to 49-year-old heterosexual, non-drug-injecting populations, calibrated using region-specific demographic and HSV-2/HIV epidemiological data. We derived global and regional estimates of the contribution of HSV-2 to HIV infection over 10 years [the transmission population-attributable fraction (tPAF)] under 3 additive scenarios, assuming: (1) HSV-2 increases only HIV acquisition risk (conservative); (2) HSV-2 also increases HIV transmission risk (liberal); and (3) HIV or antiretroviral therapy (ART) also modifies HSV-2 transmission risk, and HSV-2 decreases ART effect on HIV transmission risk (fully liberal). RESULTS: Under the conservative scenario, the predicted tPAF was 37.3% (95% uncertainty interval: 33.4%-43.2%), and an estimated 5.6 (4.5-7.0) million incident heterosexual HIV infections were due to HSV-2 globally over 2009-2018. The contribution of HSV-2 to HIV infections was largest for the African region [tPAF = 42.6% (38.0%-51.2%)] and lowest for the European region [tPAF = 11.2% (7.9%-13.8%)]. The tPAF was higher among female sex workers, their clients, and older populations, reflecting their higher HSV-2 prevalence. The tPAF was approximately 50% and 1.3- to 2.4-fold higher for the liberal or fully liberal scenario than the conservative scenario across regions. CONCLUSION: HSV-2 may have contributed to at least 37% of incident HIV infections in the past decade worldwide, and even more in Africa, and may continue to do so despite increased ART access unless future improved HSV-2 control measures, such as vaccines, become available.

Increases in HIV Incidence Following Receptive Anal Intercourse Among Women: A Systematic Review and Meta-analysis.

Receptive anal intercourse (RAI) carries a greater per-act risk of HIV acquisition than receptive vaginal intercourse (RVI) and may influence HIV epidemics driven by heterosexual sex. This systematic review explores the association between RAI and incident HIV among women, globally. We searched Embase and Medline through September 2018 for longitudinal studies reporting crude (cRR) or adjusted (aRR) relative risks of HIV acquisition by RAI practice among women. Of 27,563 articles identified, 17 eligible studies were included. We pooled independent study estimates using random-effects models. Women reporting RAI were more likely to acquire HIV than women not reporting RAI (pooled cRR = 1.56 95% CI 1.03-2.38, N = 18, I2 = 72%; pooled aRR = 2.23, 1.01-4.92, N = 5, I2 = 70%). In subgroup analyses the association was lower for women in Africa (pooled cRR = 1.16, N = 13, I2 = 21%) than outside Africa (pooled cRR = 4.10, N = 5, I2 = 79%) and for high-risk (pooled aRR = 1.69, N = 4, I2 = 63%) than general-risk women (pooled aRR = 8.50, N = 1). Interview method slightly influenced cRR estimates (p value = 0.04). In leave-one-out sensitivity analyses pooled estimates were generally robust to removing individual study estimates. Main limitations included poor exposure definition, incomplete adjustment for confounders, particularly condom use, and use of non-confidential interview methods. More and better data are needed to explain differences in risk by world region and risk population. Women require better counselling and greater choice in prevention modalities that are effective during RVI and RAI.

HIV testing and engagement with the HIV treatment cascade among men who have sex with men in Africa: a systematic review and meta-analysis.

BACKGROUND: HIV disproportionately affects gay, bisexual, and other men who have sex with men (MSM) in Africa, where many countries criminalise same-sex behaviour. We assessed changes in the engagement of African MSM with HIV testing and treatment cascade stages over time, and the effect of anti-LGBT legislation and stigma. METHODS: We systematically searched Embase, Global Health, MEDLINE, Scopus, and Web of Science for peer-reviewed cross-sectional or longitudinal studies recruiting at least ten MSM, published from Jan 1, 1980, to Oct 10, 2018. We extracted or derived estimates of HIV testing, engagement with the HIV treatment cascade, or both among African MSM from published reports. We derived pooled estimates using inverse-variance random-effects models. We used subgroup and meta-regression analysis to assess associations between testing and status awareness outcomes and study and participant characteristics, including the severity of country-level anti-LGBT legislation. FINDINGS: Our searches identified 75 independent eligible studies that provided estimates for 44 993 MSM across one or more of five testing and treatment cascade outcomes. HIV testing increased significantly over time overall, with pooled proportions of MSM ever tested for HIV of 67·3% (95% CI 62·1-72·3; 44 estimates) and tested in the past 12 months of 50·1% (42·4-57·8, 31 estimates) after 2011, which were 14·8 percentage points and 17·9 percentage points higher than before 2011, respectively. After 2011, ever testing was highest in southern Africa (80·0%), and lowest in northern Africa (34·4%), with the greatest increase in western Africa (from 42·4% to 70·9%). Levels of testing ever, in the past 12 months, and status awareness were statistically significantly lower in countries with the most severe anti-LGBT legislation compared with countries with the least severe legislation (57·4% vs 71·6%, p=0·0056; 35·5% vs 49·3%, p=0·010; 6·7% vs 22·0%, p=0·0050). Few estimates were available for later stages of the treatment cascade. Available data after 2011 suggest that the pooled proportion of MSM HIV-positive aware has remained low (18·5%, 12·5-25·3; 28 estimates), whereas proportions of current antiretroviral therapy (ART) use were 23·7% (15·5-33·0; 13 estimates) among all MSM living with HIV and 60·1% (48·6-71·1; five estimates) among MSM HIV-positive aware of their status. Pooled levels of viral suppression among MSM currently on ART were 75·6% (64·4-85·5; four estimates), but only 24·7% (18·8-31·2; four estimates) among all MSM living with HIV. INTERPRETATION: Despite improvements in HIV testing among MSM in Africa, HIV status awareness, ART coverage, and viral suppression remain much lower than required to achieve UNAIDS 90-90-90 targets. Further studies are urgently needed to provide more accurate estimates of levels of status awareness, engagement in care, ART coverage, and viral suppression among MSM to inform prevention efforts aimed at improving access to HIV services for MSM. Severe anti-LGBT legislation might be associated with lower HIV testing and status awareness; therefore, further research is needed to assess the effect of such legislation on HIV testing and engagement with the HIV treatment cascade among MSM. FUNDING: US National Institutes of Health, UK Medical Research Council.