The contribution of intimate partner violence to vertical HIV transmission: a modelling analysis of 46 African countries.

BACKGROUND: Addressing gender inequities could be key to the elimination of vertical transmission of HIV. Women experiencing intimate partner violence (IPV) might be at an increased risk of vertical transmission due to their vulnerability to HIV acquisition and barriers to access to and retention in care. Sub-Saharan Africa, where IPV burden is among the highest globally, accounts for most new paediatric HIV infections. We aimed to examine the proportion of excess vertical transmission attributable to IPV in this region. METHODS: In this modelling analysis, we created a probability tree model of vertical HIV transmission among women aged 15-49 years in 46 African countries. We estimated the proportion of vertical transmission attributable to past-year physical or sexual IPV, or both, as an age-standardised population attributable fraction (PAF) and as excess vertical transmission risk per 1000 births among women experiencing IPV. We incorporated perinatal and postnatal vertical transmission among women who acquired HIV before pregnancy, during pregnancy, and during breastfeeding. Fertility, HIV prevalence, HIV incidence, antiretroviral therapy (ART) uptake, and ART retention varied in the model by women's IPV experience. The model was parameterised using UNAIDS' 2023 Spectrum model data, WHO's Global Database on Violence Against Women, and the peer-reviewed literature. Uncertainty intervals (95% UI) were calculated through 1000 Monte Carlo simulations. FINDINGS: Across 46 countries 13% (95% UI 6-21) of paediatric HIV infections in 2022 were attributed to IPV, corresponding to over 22 000 paediatric infections. The PAF ranged from 4% (2-7) in Niger to 28% (13-43) in Uganda. The PAF was highest among girls aged 15-19 years (20%, 8-33) and lowest among women aged 45-49 years (6%, 3-9). In southern Africa, where women's HIV prevalence is highest (23%), IPV led to 11 (5-20) additional infections per 1000 births among women affected by IPV. INTERPRETATION: IPV might be responsible for one in eight paediatric HIV infections in sub-Saharan Africa. Ending IPV could accelerate vertical transmission elimination, especially among young women who bear the highest burden of violence. FUNDING: Canadian Institutes of Health Research, Canada Research Chair, and Fonds de recherche du Québec-Santé. TRANSLATIONS: For the French, Georgian and Spanish translations of the abstract see Supplementary Materials section.

Vaccine value profile for herpes simplex virus.

Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) are chronic, highly prevalent viral infections that cause significant morbidity around the world. HSV-2 is sexually transmitted and is the leading cause of genital ulcer disease (GUD). It also increases the risk of HIV acquisition, fueling the HIV epidemic. HSV-1 is typically acquired in childhood through nonsexual contact and contributes to oral and ocular disease, but it can also be sexually transmitted to cause GUD. Both HSV-1 and HSV-2 cause neonatal herpes and neurologic disease. Given the ubiquitous nature of HSV-1 and HSV-2 infections and the limited existing prevention and control measures, vaccination would be the most efficient strategy to reduce the global burden of morbidity related to HSV infection. Vaccine strategies include prophylactic vaccination, which would prevent infection among susceptible persons and would likely be given to adolescents, and therapeutic vaccinations, which would be given to people with symptomatic genital HSV-2 infection. This document discusses the vaccine value profile of both types of vaccines. This 'Vaccine Value Profile' (VVP) for HSV is intended to provide a high-level, holistic assessment of the information and data that are currently available to inform the potential public health, economic and societal value of pipeline vaccines and vaccine-like products. This VVP was developed by subject matter experts from academia, non-profit organizations, government agencies and multi-lateral organizations. All contributors have extensive expertise on various elements of the HSV VVP and collectively aimed to identify current research and knowledge gaps. The VVP was developed using only existing and publicly available information.

Potential population-level effects of HIV self-test distribution among key populations in Côte d'Ivoire, Mali, and Senegal: a mathematical modelling analysis.

BACKGROUND: During 2019-21, the AutoTest VIH, Libre d'accéder à la connaissance de son Statut (ATLAS) programme distributed around 380 000 HIV self-testing kits to key populations, including female sex workers, men who have sex with men, and their partners, in Côte d'Ivoire, Mali, and Senegal. We aimed to estimate the effects of the ATLAS programme and national scale-up of HIV self-test distribution on HIV diagnosis, HIV treatment coverage, HIV incidence, and HIV-related mortality. METHODS: We adapted a deterministic compartmental model of HIV transmission in Côte d'Ivoire, parameterised and fitted to country-specific demographic, behavioural, HIV epidemiological, and intervention data in Côte d'Ivoire, Mali, and Senegal separately during 1980-2020. We simulated dynamics of new HIV infections, HIV diagnoses, and HIV-related deaths within scenarios with and without HIV self-test distribution among key populations. Models were separately parameterised and fitted to country-specific sets of epidemiological and intervention outcomes (stratified by sex, risk, age group, and HIV status, if available) over time within a Bayesian framework. We estimated the effects on the absolute increase in the proportion of people with HIV diagnosed at the end of 2021 for the ATLAS-only scenario and at the end of 2028 and 2038 for the HIV self-testing scale-up scenario. We estimated cumulative numbers of additional HIV diagnoses and initiations of antiretroviral therapy and the proportion and absolute numbers of new HIV infections and HIV-related deaths averted during 2019-21 and 2019-28 for the ATLAS-only scenario and during 2019-28 and 2019-38 for the HIV self-testing scale-up scenario. FINDINGS: Our model estimated that ATLAS could have led to 700 (90% uncertainty interval [UI] 500-900) additional HIV diagnoses in Côte d'Ivoire, 500 (300-900) in Mali, and 300 (50-700) in Senegal during 2019-21, a 0·4 percentage point (90% UI 0·3-0·5) increase overall by the end of 2021. During 2019-28, ATLAS was estimated to avert 1900 (90% UI 1300-2700) new HIV infections and 600 (400-800) HIV-related deaths across the three countries, of which 38·6% (90% UI 31·8-48·3) of new infections and 70·1% (60·4-77·3) of HIV-related deaths would be among key populations. ATLAS would avert 1·5% (0·8-3·1) of all HIV-related deaths across the three countries during this period. Scaling up HIV self-testing would avert 16·2% (90% UI 10·0-23·1) of all new HIV infections during 2019-28 in Senegal, 5·3% (3·0-8·9) in Mali, and 1·6% (1·0-2·4) in Côte d'Ivoire. HIV self-testing scale-up among key populations was estimated to increase HIV diagnosis by the end of 2028 to 1·3 percentage points (90% UI 0·8-1·9) in Côte d'Ivoire, 10·6 percentage points (5·3-16·8) in Senegal, and 3·6 percentage points (2·0-6·4) in Mali. INTERPRETATION: Scaling up HIV self-test distribution among key populations in western Africa could attenuate disparities in access to HIV testing and reduce infections and deaths among key populations and their partners. FUNDING: Unitaid, Solthis, the UK Medical Research Council Centre for Global Infectious Disease Analysis, the EU European & Developing Countries Clinical Trials Partnership programme, and the Wellcome Trust.

Cost-effectiveness analysis of community-led HIV self-testing among key populations in Côte d'Ivoire, Mali, and Senegal.

INTRODUCTION: HIV self-testing (HIVST) is a promising strategy to improve diagnosis coverage among key populations (KP). The ATLAS (Auto Test VIH, Libre d'Accéder à la connaissance de son Statut) programme implemented HIVST in three West African countries, distributing over 380,000 kits up between 2019 and 2021, focussing on community-led distribution by KP to their peers and subsequent secondary distribution to their partners and clients. We aim to evaluate the cost-effectiveness of community-led HIVST in Côte d'Ivoire, Mali and Senegal. METHODS: An HIV transmission dynamics model was adapted and calibrated to country-specific epidemiological data and used to predict the impact of HIVST. We considered the distribution of HIVST among two KP-female sex workers (FSW), and men who have sex with men (MSM)-and their sexual partners and clients. We compared the cost-effectiveness of two scenarios against a counterfactual without HIVST over a 20-year horizon (2019-2039). The ATLAS-only scenario mimicked the 2-year implemented ATLAS programme, whereas the ATLAS-scale-up scenario achieved 95% coverage of HIVST distribution among FSW and MSM by 2025 onwards. The primary outcome is the number of disability-adjusted life-years (DALY) averted. Scenarios were compared using incremental cost-effectiveness ratios (ICERs). Costing was performed using a healthcare provider's perspective. Costs were discounted at 4%, converted to $USD 2022 and estimated using a cost-function to accommodate economies of scale. RESULTS: The ATLAS-only scenario was highly cost-effective over 20 years, even at low willingness-to-pay thresholds. The median ICERs were $126 ($88-$210) per DALY averted in Côte d'Ivoire, $92 ($88-$210) in Mali and 27$ ($88-$210) in Senegal. Scaling-up the ATLAS programme would also be cost-effective, and substantial epidemiological impacts would be achieved. The ICERs for the scale-up scenario were $199 ($122-$338) per DALY averted in Côte d'Ivoire, $224 ($118-$415) in Mali and $61 ($18-$128) in Senegal. CONCLUSIONS: Both the implemented and the potential scale-up of community-led HIVST programmes in West Africa, where KP are important to overall transmission dynamics, have the potential to be highly cost-effective, as compared to a scenario without HIVST. These findings support the scale-up of community-led HIVST to reach populations that otherwise may not access conventional testing services.

The impact of past HIV interventions and diagnosis gaps on new HIV acquisitions, transmissions, and HIV-related deaths in Côte d'Ivoire, Mali, and Senegal.

OBJECTIVES: To estimate the epidemiological impact of past HIV interventions and the magnitude and contribution of undiagnosed HIV among different risk groups on new HIV acquisitions in Côte d'Ivoire, Mali and Senegal. DESIGN: HIV transmission dynamic models among the overall population and key populations [female sex workers (FSW), their clients, and MSM]. METHODS: Models were independently parameterized and calibrated for each set of country-specific demographic, behavioural, and epidemiological data. We estimated the fraction of new HIV infections over 2012-2021 averted by condom use and antiretroviral therapy (ART) uptake among key population and nonkey population, the direct and indirect contribution of specific groups to new infections [transmission population-attributable fraction (tPAF)] over 2012-2021 due to prevention gaps, and the distribution of undiagnosed PWH by risk group in January 2022 and their tPAF over 2022-2031. RESULTS: Condom use and ART may have averted 81-88% of new HIV infections over 2012-2021 across countries, mostly because of condom use by key population. The tPAF of all key populations combined over 2012-2021 varied between 27% (Côte d'Ivoire) and 79% (Senegal). Male key population (clients of FSW and MSM) contributed most to new infections (>60% in Mali and Senegal) owing to their higher HIV prevalence and larger prevention gaps. In 2022, men represented 56% of all PWH with an undiagnosed infection in Côte d'Ivoire (male key population = 15%), 46% in Mali (male key population = 23%), and 69% in Senegal (male key population = 55%). If HIV testing and ART initiation rates remain at current levels, 20% of new HIV infections could be due to undiagnosed key population PWH in Côte d'Ivoire over 2022-2031, 53% in Mali, and 65% in Senegal. CONCLUSION: Substantial HIV diagnosis gaps remain in Western Africa, especially among male key population. Addressing these gaps is key to impacting the HIV epidemics in the region and achieving the goal of ending AIDS by 2030.

Guidance for triangulating data and estimates of HIV prevalence among pregnant women and coverage of PMTCT using the Spectrum AIDS Impact Module.

Background: Most countries use the Spectrum AIDS Impact Module (Spectrum-AIM), antenatal care routine HIV testing, and antiretroviral treatment data to estimate HIV prevalence among pregnant women. Non-representative programme data may lead to inaccurate estimates HIV prevalence and treatment coverage for pregnant women. Setting: 154 locations in 126 countries. Methods: Using 2023 UNAIDS HIV estimates, we calculated three ratios: (1) HIV prevalence among pregnant women to all women 15-49y (prevalence), (2) ART coverage before pregnancy to women 15-49y ART coverage (ART pre-pregnancy), and (3) ART coverage at delivery to women 15-49y ART coverage (PMTCT coverage). We developed an algorithm to identify and adjust inconsistent results within regional ranges in Spectrum-AIM, illustrated using Burkina Faso's estimates. Results: In 2022, the mean regional ratio of prevalence among pregnant women to all women ranged from 0.68 to 0.95. ART coverage pre-pregnancy ranged by region from 0.40 to 1.22 times ART coverage among all women. Mean regional PMTCT coverage ratios ranged from 0.85 to 1.51. The prevalence ratio in Burkina Faso was 1.59, above the typical range 0.62-1.04 in western and central Africa. Antenatal clinics reported more PMTCT recipients than estimated HIV-positive pregnant women from 2015 to 2019. We adjusted inputted PMTCT programme data to enable consistency of HIV prevalence among pregnant women from programmatic routine HIV testing at antenatal clinics with values typical for Western and central Africa. Conclusion: These ratios offer Spectrum-AIM users a tool to gauge the consistency of their HIV prevalence and treatment coverage estimates among pregnant women with other countries in the region.

Aetiology of vaginal discharge, urethral discharge, and genital ulcer in sub-Saharan Africa: A systematic review and meta-regression.

BACKGROUND: Syndromic management is widely used to treat symptomatic sexually transmitted infections in settings without aetiologic diagnostics. However, underlying aetiologies and consequent treatment suitability are uncertain without regular assessment. This systematic review estimated the distribution, trends, and determinants of aetiologies for vaginal discharge, urethral discharge, and genital ulcer in sub-Saharan Africa (SSA). METHODS AND FINDINGS: We searched Embase, MEDLINE, Global Health, Web of Science, and grey literature from inception until December 20, 2023, for observational studies reporting aetiologic diagnoses among symptomatic populations in SSA. We adjusted observations for diagnostic test performance, used generalised linear mixed-effects meta-regressions to generate estimates, and critically appraised studies using an adapted Joanna Briggs Institute checklist. Of 4,418 identified records, 206 reports were included from 190 studies in 32 countries conducted between 1969 and 2022. In 2015, estimated primary aetiologies for vaginal discharge were candidiasis (69.4% [95% confidence interval (CI): 44.3% to 86.6%], n = 50), bacterial vaginosis (50.0% [95% CI: 32.3% to 67.8%], n = 39), chlamydia (16.2% [95% CI: 8.6% to 28.5%], n = 50), and trichomoniasis (12.9% [95% CI: 7.7% to 20.7%], n = 80); for urethral discharge were gonorrhoea (77.1% [95% CI: 68.1% to 84.1%], n = 68) and chlamydia (21.9% [95% CI: 15.4% to 30.3%], n = 48); and for genital ulcer were herpes simplex virus type 2 (HSV-2) (48.3% [95% CI: 32.9% to 64.1%], n = 47) and syphilis (9.3% [95% CI: 6.4% to 13.4%], n = 117). Temporal variation was substantial, particularly for genital ulcer where HSV-2 replaced chancroid as the primary cause. Aetiologic distributions for each symptom were largely the same across regions and population strata, despite HIV status and age being significantly associated with several infection diagnoses. Limitations of the review include the absence of studies in 16 of 48 SSA countries, substantial heterogeneity in study observations, and impeded assessment of this variability due to incomplete or inconsistent reporting across studies. CONCLUSIONS: In our study, syndrome aetiologies in SSA aligned with World Health Organization guidelines without strong evidence of geographic or demographic variation, supporting broad guideline applicability. Temporal changes underscore the importance of regular aetiologic re-assessment for effective syndromic management. PROSPERO NUMBER: CRD42022348045.

The impact of policing and homelessness on violence experienced by women who sell sex in London: a modelling study.

Street-based sex workers experience considerable homelessness, drug use and police enforcement, making them vulnerable to violence from clients and other perpetrators. We used a deterministic compartmental model of street-based sex workers in London to estimate whether displacement by police and unstable housing/homelessness increases client violence. The model was parameterized and calibrated using data from a cohort study of sex workers, to the baseline percentage homeless (64%), experiencing recent client violence (72%), or recent displacement (78%), and the odds ratios of experiencing violence if homeless (1.97, 95% confidence interval 0.88-4.43) or displaced (4.79, 1.99-12.11), or of experiencing displacement if homeless (3.60, 1.59-8.17). Ending homelessness and police displacement reduces violence by 67% (95% credible interval 53-81%). The effects are non-linear; halving the rate of policing or becoming homeless reduces violence by 5.7% (3.5-10.3%) or 6.7% (3.7-10.2%), respectively. Modelled interventions have small impact with violence reducing by: 5.1% (2.1-11.4%) if the rate of becoming housed increases from 1.4 to 3.2 per person-year (Housing First initiative); 3.9% (2.4-6.9%) if the rate of policing reduces by 39% (level if recent increases had not occurred); and 10.2% (5.9-19.6%) in combination. Violence reduces by 26.5% (22.6-28.2%) if half of housed sex workers transition to indoor sex work. If homelessness decreased and policing increased as occurred during the COVID-19 pandemic in 2020, the impact on violence is negligible, decreasing by 0.7% (8.7% decrease-4.1% increase). Increasing housing and reducing policing among street-based sex workers could substantially reduce violence, but large changes are needed.

Burden and Trends of Symptomatic Sexually Transmitted Infections in Malawi From 2000 to 2021: Comparative Analysis of Survey and Case Report Data.

BACKGROUND: In settings without etiologic testing for sexually transmitted infections (STIs), programs rely on STI symptom data to inform priorities. To evaluate whether self-reported STI symptoms in household surveys consistently represent the STI burden, we compared symptomatic infection rates between survey self-reporting and health facility case reporting in Malawi. METHODS: We analyzed self-reported symptoms and treatment seeking in the past year among sexually active adults from 4 Malawi Demographic and Health Surveys between 2000 and 2015. Bayesian mixed-effects models were used to estimate temporal trends, spatial variation, and sociodemographic determinants. Survey reporting was compared with health facility syndromic diagnoses between 2014 and 2021. RESULTS: In surveys, 11.0% (95% confidence interval, 10.7%-11.4%) of adults reported STI or STI-related symptoms in the last year, of whom 54.2% (52.8%-55.7%) sought treatment. In facilities, the mean annual symptomatic case diagnosis rate was 3.3%. Survey-reported treatment in the last year was 3.8% (95% credible interval, 2.3%-6.1%) for genital ulcer, 3.8% (2.0%-6.7%) for vaginal discharge, and 2.6% (1.2%-4.7%) for urethral discharge. Mean annual diagnosis rates at facilities were 0.5% for genital ulcer, 2.2% for vaginal discharge, and 2.0% for urethral discharge. Both data sources indicated a higher burden of symptoms among women, individuals older than 25 years, and those in Southern Malawi. CONCLUSIONS: Survey and facility case reports indicated similar spatial and demographic patterns of STI symptom burden and care seeking, but implied large differences in the magnitude and relative burden of symptoms, particularly genital ulcer, which could affect program priorities. Targeted etiologic surveillance would improve interpretation of these data to enable more comprehensive STI surveillance.

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.

Population-level effectiveness of pre-exposure prophylaxis for HIV prevention among men who have sex with men in Montréal (Canada): a modelling study of surveillance and survey data.

INTRODUCTION: HIV pre-exposure prophylaxis (PrEP) has been recommended and partly subsidized in Québec, Canada, since 2013. We evaluated the population-level impact of PrEP on HIV transmission among men who have sex with men (MSM) in Montréal, Québec's largest city, over 2013-2021. METHODS: We used an agent-based mathematical model of sexual HIV transmission to estimate the fraction of HIV acquisitions averted by PrEP compared to a counterfactual scenario without PrEP. The model was calibrated to local MSM survey, surveillance, and cohort data and accounted for COVID-19 pandemic impacts on sexual activity, HIV prevention, and care. PrEP was modelled from 2013 onwards, assuming 86% individual-level effectiveness. The PrEP eligibility criteria were: any anal sex unprotected by condoms (past 6 months) and either multiple partnerships (past 6 months) or multiple uses of post-exposure prophylaxis (lifetime). To assess potential optimization strategies, we modelled hypothetical scenarios prioritizing PrEP to MSM with high sexual activity (≥11 anal sex partners annually) or aged ⩽45 years, increasing coverage to levels achieved in Vancouver, Canada (where PrEP is free-of-charge), and improving retention. RESULTS: Over 2013-2021, the estimated annual HIV incidence decreased from 0.4 (90% credible interval [CrI]: 0.3-0.6) to 0.2 (90% CrI: 0.1-0.2) per 100 person-years. PrEP coverage among HIV-negative MSM remained low until 2015 (<1%). Afterwards, coverage increased to a maximum of 10% of all HIV-negative MSM, or about 16% of the 62% PrEP-eligible HIV-negative MSM in 2020. Over 2015-2021, PrEP averted an estimated 20% (90% CrI: 11%-30%) of cumulative HIV acquisitions. The hypothetical scenarios modelled showed that, at the same coverage level, prioritizing PrEP to high sexual activity MSM could have averted 30% (90% CrI: 19%-42%) of HIV acquisitions from 2015-2021. Even larger impacts could have resulted from higher coverage. Under the provincial eligibility criteria, reaching 10% coverage among HIV-negative MSM in 2015 and 30% in 2019, like attained in Vancouver, could have averted up to 63% (90% CrI: 54%-70%) of HIV acquisitions from 2015 to 2021. CONCLUSIONS: PrEP reduced population-level HIV transmission among Montréal MSM. However, our study suggests missed prevention opportunities and adds support for public policies that reduce PrEP barriers, financial or otherwise, to MSM at risk of HIV acquisition.

Association of naturally acquired type-specific HPV antibodies and subsequent HPV re-detection: systematic review and meta-analysis.

BACKGROUND: Understanding the role of naturally acquired (i.e., infection-induced) human papillomavirus (HPV) antibodies against reinfection is important given the high incidence of this sexually transmitted infection. However, the protective effect of naturally acquired antibodies in terms of the level of protection, duration, and differential effect by sex remains incompletely understood. We conducted a systematic review and a meta-analysis to (1) strengthen the evidence on the association between HPV antibodies acquired through past infection and subsequent type-specific HPV detection, (2) investigate the potential influence of type-specific HPV antibody levels, and (3) assess differential effects by HIV status. METHODS: We searched Embase and Medline databases to identify studies which prospectively assessed the risk of type-specific HPV detection by baseline homologous HPV serostatus among unvaccinated individuals. Random-effect models were used to pool the measures of association of naturally acquired HPV antibodies against subsequent incident detection and persistent HPV positivity. Sources of heterogeneity for each type were assessed through subgroup analyses stratified by sex, anatomical site of infection, male sexual orientation, age group, and length of follow-up period. Evidence of a dose-response relationship of the association between levels of baseline HPV antibodies and type-specific HPV detection was assessed. Finally, we pooled estimates from publications reporting associations between HPV serostatus and type-specific HPV detection by baseline HIV status. RESULTS: We identified 26 publications (16 independent studies, with 62,363 participants) reporting associations between baseline HPV serostatus and incident HPV detection, mainly for HPV-16 and HPV-18, the most detected HPV type. We found evidence of protective effects of baseline HPV seropositivity and subsequent detection of HPV DNA (0.70, 95% CI 0.61-0.80, NE = 11) and persistent HPV positivity (0.65, 95% CI 0.42-1.01, NE = 5) mainly for HPV-16 among females, but not among males, nor for HPV-18. Estimates from 8 studies suggested a negative dose-response relationship between HPV antibody level and subsequent detection among females. Finally, we did not observe any differential effect by baseline HIV status due to the limited number of studies available. CONCLUSION: We did not find evidence that naturally acquired HPV antibodies protect against subsequent HPV positivity in males and provide only modest protection among females for HPV-16. One potential limitation to the interpretation of these findings is potential misclassification biases due to different causes.

Efficacy estimates of oral pre-exposure prophylaxis for HIV prevention in cisgender women with partial adherence.

Pre-exposure prophylaxis (PrEP) with tenofovir (TFV) disoproxil fumarate and emtricitabine administered orally daily is effective in preventing human immunodeficiency virus (HIV) acquisition in both men and women with sufficient adherence; however, the adherence-efficacy relationship in cisgender women has not been well established. We calculated the adherence-efficacy curve for cisgender women by using HIV incidence and plasma TFV concentration data from three trials (FEM-PrEP, VOICE and Partners PrEP). We imputed TFV diphosphate (TFV-DP) concentrations, a measure of long-term adherence, from TFV quantification by using data from the HIV Prevention Trials Network 082 study, which measured both TFV-DP and TFV concentrations. Two, four and seven pills per week reduced HIV incidence by 59.3% (95% credible interval (CrI) 29.9-95.8%), 83.8% (95% CI 51.7-99.8%) and 95.9% (95% CI 72.6-100%), respectively. Our adherence-efficacy curve can be validated and updated by HIV prevention studies that directly measure TFV-DP concentrations. The curve suggests that high adherence confers high protection in cisgender women. However, the lower efficacy with partial adherence highlights the need for new PrEP products and interventions to increase adherence.

Characteristics of male perpetrators of intimate partner violence and implications for women's HIV status: A pooled analysis of cohabiting couples from 27 countries in Africa (2000-2020).

Intimate partner violence (IPV) may increase women's HIV acquisition risk. Still, knowledge on pathways through which IPV exacerbates HIV burden is emerging. We examined the individual and partnership-level characteristics of male perpetrators of physical and/or sexual IPV and considered their implications for women's HIV status. We pooled individual-level data from nationally representative, cross-sectional surveys in 27 countries in Africa (2000-2020) with information on past-year physical and/or sexual IPV and HIV serology among cohabiting couples (≥15 years). Current partners of women experiencing past-year IPV were assumed to be IPV perpetrators. We used Poisson regression, based on Generalized Estimating Equations, to estimate prevalence ratios (PR) for male partner and partnership-level factors associated with perpetration of IPV, and men's HIV status. We used marginal standardization to estimate the adjusted risk differences (aRD) quantifying the incremental effect of IPV on women's risk of living with HIV, beyond the risk from their partners' HIV status. Models were adjusted for survey fixed effects and potential confounders. In the 48 surveys available from 27 countries (N = 111,659 couples), one-fifth of women reported that their partner had perpetrated IPV in the past year. Men who perpetrated IPV were more likely to be living with HIV (aPR = 1.09; 95%CI: 1.01-1.16). The aRD for living with HIV among women aged 15-24 whose partners were HIV seropositive and perpetrated past-year IPV was 30% (95%CI: 26%-35%), compared to women whose partners were HIV seronegative and did not perpetrate IPV. Compared to the same group, aRD among women whose partner was HIV seropositive without perpetrating IPV was 27% (95%CI: 23%-30%). Men who perpetrated IPV are more likely to be living with HIV. IPV is associated with a slight increase in young women's risk of living with HIV beyond the risk of having an HIV seropositive partner, which suggests the mutually reinforcing effects of HIV/IPV.

Potential population-level effectiveness of one-dose HPV vaccination in low-income and middle-income countries: a mathematical modelling analysis.

BACKGROUND: Given the accumulating evidence that one-dose vaccination could provide high and sustained protection against human papillomavirus (HPV) infection and related diseases, we examined the population-level effectiveness and efficiency of one-dose HPV vaccination of girls compared with two-dose vaccination, using mathematical modelling. METHODS: In this mathematical modelling study, we used HPV-ADVISE LMIC, an individual-based transmission-dynamic model independently calibrated to four epidemiologically diverse low-income and middle-income countries (LMICs; India, Nigeria, Uganda, and Viet Nam). We parameterised and calibrated the model using sexual behaviour and epidemiological data identified from international population-based datasets and the literature. All base-case vaccination scenarios start in 2023 with the nonavalent vaccine and assumed 80% vaccination coverage with one or two doses. We assumed that two doses of vaccine provide 100% efficacy against vaccine-type infections and a lifelong duration of protection. We examined a non-inferior vaccination scenario for one dose compared with two doses, pessimistic scenarios of lower one-dose vaccine efficacy (85%) or a shorter duration of protection (ie, 20 or 30 years), and the effectiveness of a mitigation scenario in which schedules would switch from one dose to two doses. We also did sensitivity analyses by varying vaccination coverage. We used three outcomes: the relative reduction in cervical cancer incidence, the number of cervical cancers averted, and the number of vaccine doses needed to prevent one cervical cancer. FINDINGS: Assuming non-inferior vaccine characteristics for one dose compared with two doses, the model projections show that two-dose or one-dose routine vaccination of girls aged 9 years (with a multi-age cohort vaccination of girls aged 10-14 years) would avert 12·0 million (80% UI 9·5-14·5) cervical cancers in India, 4·7 million (3·4-5·8) in Nigeria, 2·3 million (1·9-2·6) in Uganda, and 0·4 million (0·2-0·5) in Viet Nam over 100 years. Under pessimistic assumptions of lower one-dose efficacy (85%) or a shorter duration of protection (ie, 30 years), one-dose routine vaccination would avert 69% (61-80) to 94% (92-96) of the cervical cancers averted with two-dose routine vaccination. However, when assuming a duration of protection of 20 years, one-dose routine vaccination would avert substantially fewer cervical cancers (ie, 35% [26-44] to 69% [65-71] of the cervical cancers averted with two-dose routine vaccination). A switch from one-dose to two-dose routine vaccination of girls aged 9 years, with a one-dose catch-up of girls aged 10-14 years, 5 years after the start of the vaccination programme, could mitigate potential losses in cervical cancer prevention from a short one-dose duration of protection (averting 92% [83-98] to 99% [97-100]) of the cervical cancers averted with two-dose routine vaccination). One-dose routine vaccination would result in fewer doses needed to prevent one cervical cancer than two-dose routine vaccination, even if the duration of protection is as low as 20 years. Finally, for countries with two-dose routine vaccination, adding one-dose multi-age cohort vaccination in the first year would provide similar benefits as a two-dose multi-age cohort vaccination, and would be more efficient even under the pessimistic assumptions of lower one-dose vaccine efficacy or duration of protection. INTERPRETATION: One-dose routine vaccination could avert most of the cervical cancers averted with two-dose vaccination while being more efficient, provided the duration of one-dose protection is greater than 20-30 years (depending on the LMIC). The doses saved by introducing one-dose routine vaccination could offer the opportunity to vaccinate girls before they age out of the vaccination window of 9-14 years and, potentially, to vaccinate boys or older age groups. FUNDING: Fonds de recherche du Québec-Santé, Digital Research Alliance of Canada, Bill & Melinda Gates Foundation.

Can HIV self-testing reach first-time testers? A telephone survey among self-test end users in Côte d'Ivoire, Mali, and Senegal.

BACKGROUND: Coverage of HIV testing remains sub-optimal in West Africa. Between 2019 and 2022, the ATLAS program distributed ~400 000 oral HIV self-tests (HIVST) in Côte d'Ivoire, Mali, and Senegal, prioritising female sex workers (FSW) and men having sex with men (MSM), and relying on secondary redistribution of HIVST to partners, peers and clients to reach individuals not tested through conventional testing. This study assesses the proportion of first-time testers among HIVST users and the associated factors. METHODS: A phone-based survey was implemented among HIVST users recruited using dedicated leaflets inviting them to anonymously call a free phone number. We collected socio-demographics, sexual behaviours, HIV testing history, HIVST use, and satisfaction with HIVST. We reported the proportion of first-time testers and computed associated factors using logistic regression. RESULTS: Between March and June 2021, 2 615 participants were recruited for 50 940 distributed HIVST (participation rate: 5.1%). Among participants, 30% received their HIVST kit through secondary distribution (from a friend, sexual partner, family member, or colleague). The proportion who had never tested for HIV before HIVST (first-time testers) was 41%. The main factors associated with being a first-time tester were sex, age group, education level, condom use, and secondary distribution. A higher proportion was observed among those aged 24 years or less (55% vs 32% for 25-34, aOR: 0.37 [95%CI: 0.30-0.44], and 26% for 35 years or more, aOR: 0.28 [0.21-0.37]); those less educated (48% for none/primary education vs 45% for secondary education, aOR: 0.60 [0.47-0.77], and 29% for higher education, aOR: 0.33 [0.25-0.44]). A lower proportion was observed among women (37% vs 43%, aOR: 0.49 [0.40-0.60]); those reporting always using a condom over the last year (36% vs 51% for those reporting never using them, aOR: 2.02 [1.59-2.56]); and those who received their HISVST kit through primary distribution (39% vs 46% for secondary distribution, aOR: 1.32 [1.08-1.60]). CONCLUSION: ATLAS HIVST strategy, including secondary distribution, successfully reached a significant proportion of first-time testers. HIVST has the potential to reach underserved populations and contribute to the expansion of HIV testing services in West Africa.

Population-level impact of expanding PrEP coverage by offering long-acting injectable PrEP to MSM in three high-resource settings: a model comparison analysis.

INTRODUCTION: Long-acting injectable cabotegravir (CAB-LA) demonstrated superiority to daily tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for HIV pre-exposure prophylaxis (PrEP) in the HPTN 083/084 trials. We compared the potential impact of expanding PrEP coverage by offering CAB-LA to men who have sex with men (MSM) in Atlanta (US), Montreal (Canada) and the Netherlands, settings with different HIV epidemics. METHODS: Three risk-stratified HIV transmission models were independently parameterized and calibrated to local data. In Atlanta, Montreal and the Netherlands, the models, respectively, estimated mean TDF/FTC coverage starting at 29%, 7% and 4% in 2022, and projected HIV incidence per 100 person-years (PY), respectively, decreasing from 2.06 to 1.62, 0.08 to 0.03 and 0.07 to 0.001 by 2042. Expansion of PrEP coverage was simulated by recruiting new CAB-LA users and by switching different proportions of TDF/FTC users to CAB-LA. Population effectiveness and efficiency of PrEP expansions were evaluated over 20 years in comparison to baseline scenarios with TDF/FTC only. RESULTS: Increasing PrEP coverage by 11 percentage points (pp) from 29% to 40% by 2032 was expected to avert a median 36% of new HIV acquisitions in Atlanta. Substantially larger increases (by 33 or 26 pp) in PrEP coverage (to 40% or 30%) were needed to achieve comparable reductions in Montreal and the Netherlands, respectively. A median 17 additional PYs on PrEP were needed to prevent one acquisition in Atlanta with 40% PrEP coverage, compared to 1000+ in Montreal and 4000+ in the Netherlands. Reaching 50% PrEP coverage by 2032 by recruiting CAB-LA users among PrEP-eligible MSM could avert >45% of new HIV acquisitions in all settings. Achieving targeted coverage 5 years earlier increased the impact by 5-10 pp. In the Atlanta model, PrEP expansions achieving 40% and 50% coverage reduced differences in PrEP access between PrEP-indicated White and Black MSM from 23 to 9 pp and 4 pp, respectively. CONCLUSIONS: Achieving high PrEP coverage by offering CAB-LA can impact the HIV epidemic substantially if rolled out without delays. These PrEP expansions may be efficient in settings with high HIV incidence (like Atlanta) but not in settings with low HIV incidence (like Montreal and the Netherlands).

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.