Search

There is interest in expanding ART to prevent HIV transmission, but in the group with the highest levels of ART use, men who have sex with men (MSM), numbers of new infections have not decreased as coverage has increased for reasons which remain unclear. We analysed data on the HIV epidemic in MSM in the UK from a range of surveillance sources using a individual-based simulation model, allowing us to reconstruct the epidemic's main features. Model runs using parameter sets found to result in good model fit were used to infer changes in HIV-incidence and risk behaviour. Our results indicate that HIV incidence has increased (estimated mean incidence 0.30/100 person-years 1990-1997, 0.45/100 py 1998-2010), associated with a modest (26%) rise in condomless sex. Our model allows us to explore counter-factual scenarios: had ART not been introduced, but the rise in condomless sex had still occurred, then incidence 2006-2010 would have been 68% higher (95% CI 62% to 74%); a policy of ART initiation in all diagnosed with HIV from 2001 would have resulted in 32% lower incidence (95% CI 27% to 37%); had levels of HIV testing been higher (68% tested/year instead of 25%) incidence would have been an estimated 25% lower; a combination of higher testing and ART at diagnosis would have resulted in 62% lower incidence; cessation of all condom use in 2000 was predicted to result in a 424% increase in incidence. We conclude that a rise in HIV-incidence has occurred in MSM in the UK despite an only modest increase in levels of condomless sex in the era of ART. ART has almost certainly exerted a limiting effect on incidence. Much higher rates of HIV testing combined with initiation of ART at diagnosis would be likely to lead to substantial reductions in HIV. However, before advocating such a policy for all MSM we await data from well-powered randomized trials of the individual health risk of ART initiation at CD4>350 cells/mm3, and from studies of the effect of ART on infectivity through anal sex. Increased condom use should be promoted to avoid the erosion of the benefits of ART and to prevent other serious sexually transmitted infections. [ABSTRACT FROM AUTHOR]

Background: In all health-care systems, decisions need to be made regarding allocation of available resources. Evidence is needed for these decisions, especially in low-income countries. We aimed to estimate how health-care resources provided by the public sector were used in Malawi during 2015-19 and to estimate the effects of strengthening health-care services., Methods: For this modelling study, we used the Thanzi La Onse model, an individual-based simulation model. The scope of the model was health care provided by the public sector in Malawi during 2015-19. Health-care services were delivered during health-care system interaction (HSI) events, which we characterised as occurring at a particular facility level and requiring a particular number of appointments. We developed mechanistic models for the causes of death and disability that were estimated to account for approximately 81% of deaths and approximately 72% of disability-adjusted life-years (DALYs) in Malawi during 2015-19, according to the Global Burden of Disease (GBD) estimates; we computed DALYs incurred in the population as the sum of years of life lost and years lived with disability. The disease models could interact with one another and with the underlying properties of each person. Each person in the Thanzi La Onse model had specific properties (eg, sex, district of residence, wealth percentile, smoking status, and BMI, among others), for which we measured distribution and evolution over time using demographic and health survey data. We also estimated the effect of different types of health-care system improvement., Findings: We estimated that the public-sector health-care system in Malawi averted 41·2 million DALYs (95% UI 38·6-43·8) during 2015-19, approximately half of the 84·3 million DALYs (81·5-86·9) that the population would otherwise have incurred. DALYs averted were heavily skewed to children aged 0-4 years due to services averting DALYs that would be caused by acute lower respiratory tract infection, HIV or AIDS, malaria, or neonatal disorders. DALYs averted among adults were mostly attributed to HIV or AIDS and tuberculosis. Under a scenario whereby each appointment took the time expected and health-care workers did not work for longer than contracted, the health-care system in Malawi during 2015-19 would have averted only 19·1 million DALYs (95% UI 17·1-22·4), suggesting that approximately 21·3 million DALYS (20·0-23·6) of total effect were derived through overwork of health-care workers. If people becoming ill immediately accessed care, all referrals were successfully completed, diagnostic accuracy of health-care workers was as good as possible, and consumables (ie, medicines) were always available, 28·2% (95% UI 25·7-30·9) more DALYS (ie, 12·2 million DALYs [95% UI 10·9-13·8]) could be averted., Interpretation: The health-care system in Malawi provides substantial health gains with scarce resources. Strengthening interventions could potentially increase these gains, so should be a priority for investigation and investment. An individual-based simulation model of health-care service delivery is valuable for health-care system planning and strengthening., Funding: The Wellcome Trust, UK Research and Innovation, the UK Medical Research Council, and Community Jameel., Competing Interests: Declaration of interests TBH receives research funding from the UK Medical Research Council, UK Research and Innovation, and The Wellcome Trust, paid to their institution. NA receives research funding from the UK Medical Research Council and the Bill & Melinda Gates Foundation, paid to their institution. VC receives research funding from the UK Medical Research Council and UK Research and Innovation, paid to their institution, and consulting fees from Source Market Access. MC receives research funding from The Wellcome Trust, paid to their institution. JHC receives research funding from UK Research and Innovation and The Wellcome Trust, paid to their institution. JC receives research funding from UK Research and Innovation and The Wellcome Trust, paid to their institution. EJ receives research funding from UK Research and Innovation and The Wellcome Trust, paid to their institution. BLJ receives research funding from the UK Medical Research Council and the UK Department for International Development, paid to their institution. SM receives research funding from UK Research and Innovation and The Wellcome Trust, paid to their institution, and consulting fees from The Global Fund to Fight AIDS, Tuberculosis and Malaria. MM receives research funding from UK Research and Innovation and The Wellcome Trust, paid to their institution. TC receives research funding from UK Research and Innovation and The Wellcome Trust, paid to their institution; receives consulting fees from the UN Economic Commission for Africa; and is on a data safety monitoring board for a trial of adolescent mental health in Nepal. ANP receives research funding from The Wellcome Trust, paid to their institution; receives research funding from the Bill & Melinda Gates Foundation, The Wellcome Trust, the US National Institutes of Health, the UK National Institute for Health and Care Research, and the EU, paid to their institution; and receives consulting fees from WHO. All other authors declare no competing interests., (Copyright © 2025 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Mathematical modelling is a commonly utilised tool to predict the impact of policy on health outcomes globally. Given the persistently high levels of maternal and perinatal morbidity and mortality in sub-Saharan Africa, mathematical modelling is a potentially valuable tool to guide strategic planning for health and improve outcomes., Methods: The aim of this scoping review was to explore the characteristics of mathematical models and modelling studies evaluating the impact of maternal and/or perinatal healthcare interventions or services on health-related outcomes in the region. A search across three databases was conducted on 2nd November 2023 which returned 8660 potentially relevant studies, from which 60 were included in the final review. Characteristics of these studies, the interventions which were evaluated, the models utilised, and the analyses conducted were extracted and summarised., Results: Findings suggest that the popularity of modelling within this field is increasing over time with most studies published after 2015 and that population-based, deterministic, linear models were most frequently utilised, with the Lives Saved Tool being applied in over half of the reviewed studies (n = 34, 57%). Much less frequently (n = 6) models utilising system-thinking approaches, such as individual-based modelling or systems dynamics modelling, were developed and applied. Models were most applied to estimate the impact of interventions or services on maternal mortality (n = 34, 57%) or neonatal mortality outcomes (n = 39, 65%) with maternal morbidity (n = 4, 7%) and neonatal morbidity (n = 6, 10%) outcomes and stillbirth reported on much less often (n = 14, 23%)., Discussion: Going forward, given that healthcare delivery systems have long been identified as complex adaptive systems, modellers may consider the advantages of applying systems-thinking approaches to evaluate the impact of maternal and perinatal health policy. Such approaches allow for a more realistic and explicit representation of the systems- and individual- level factors which impact the effectiveness of interventions delivered within health systems., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Collins et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: To review HIV testing services (HTS) costs in sub-Saharan Africa., Design: A systematic literature review of studies published from January 2006 to October 2020., Methods: We searched ten electronic databases for studies that reported estimates for cost per person tested ($pptested) and cost per HIV-positive person identified ($ppositive) in sub-Saharan Africa. We explored variations in incremental cost estimates by testing modality (health facility-based, home-based, mobile-service, self-testing, campaign-style, and stand-alone), by primary or secondary/index HTS, and by population (general population, people living with HIV, antenatal care male partner, antenatal care/postnatal women and key populations). All costs are presented in 2019US$., Results: Sixty-five studies reported 167 cost estimates. Most reported only $pptested (90%), while (10%) reported the $ppositive. Costs were highly skewed. The lowest mean $pptested was self-testing at $12.75 (median = $11.50); primary testing at $16.63 (median = $10.68); in the general population, $14.06 (median = $10.13). The highest costs were in campaign-style at $27.64 (median = $26.70), secondary/index testing at $27.52 (median = $15.85), and antenatal male partner at $47.94 (median = $55.19). Incremental $ppositive was lowest for home-based at $297.09 (median = $246.75); primary testing $352.31 (median = $157.03); in the general population, $262.89 (median: $140.13)., Conclusion: While many studies reported the incremental costs of different HIV testing modalities, few presented full costs. Although the $pptested estimates varied widely, the costs for stand-alone, health facility, home-based, and mobile services were comparable, while substantially higher for campaign-style HTS and the lowest for HIV self-testing. Our review informs policymakers of the affordability of various HTS to ensure universal access to HIV testing., (© 2024. The Author(s).)

We described the longitudinal changes in sexual behaviour and associated factors among newly diagnosed with HIV men who have sex with men participating in a prospective observational study from a London HIV clinic (2015-2018). Participants self-completed questionnaires at baseline, months 3 and 12. Information collected included socio-demographic, sexual behaviour, health, lifestyle and social support. Trends in sexual behaviours over one year following diagnosis and associated factors were assessed using generalized estimating equations with logit link. Condomless sex (CLS) dropped from 62.2% at baseline to 47.6% at month-three but increased again to 61.8% at month-12 ( p -trend = 0.790). Serodiscordant-CLS increased between month-three and month-12 (from 13.1% to 35.6%, p -trend < 0.001). The prevalence of serodiscordant-CLS with high risk of transmitting to their partners at month-three was 10.7%. CLS was higher among men who reported recreational drug use (adjusted Odds Ratio (aOR) 3.03, 95%CI 1.47-6.24, p  = 0.003), those with undetectable viral load (aOR 2.17, 95%CI 1.22-3.84, p  = 0.008) and those who agreed with a statement "condoms are not necessary when HIV viral load is undetectable" (aOR 3.41, 95%CI 1.58-7.38, p  = 0.002). MSM continued to engage in CLS after HIV diagnosis, which coincided with U = U publications and increased throughout the study.

Objectives: In 2015 and 2016, WHO issued guidelines on HIV testing services (HTS) highlighting recommendations for a strategic mix of differentiated HTS approaches. The policy review examines the uptake of differentiated HTS approaches recommendations in national policies., Methods: Data were extracted from national policies published between January 2015 and June 2019. The WHO-recommended HTS approaches included facility-based testing, community-based testing, HIV self-testing and provider-assisted referral (or assisted partner notification). Other supportive recommendations include pre-test information, post-test counselling, lay provider testing and rapid testing. Descriptive analyses were conducted to examine inclusion of recommendations in national policies., Results: Of 194 countries worldwide, 65 published policies were identified; 24 WHO Africa region (AFR) countries (51%, 24/47), 21 WHO European region (EUR) (40%, 21/53), 6 WHO Eastern Mediterranean region (EMR) (29%, 6/21), 5 Pan-American region (AMR) (14%, 5/35), 5 Western Pacific Region (WPR) (19%, 5/27) and 4 WHO South East Asia Region (SEAR) (36%, 4/11). Only five countries included all recommendations. 63 included a minimum of one. 85% (n=55) included facility-based testing for pregnant women, 75% (n=49) facility-based testing for key populations, 74% (n=48) community-based testing for key populations, 69% (n=45) rapid testing, 57% (n=37) post-test counselling, 45% (n=29) lay provider testing, 38% (n=25) HIV self-testing, 29% (n=19) pre-test information and 25% (n=16) provider-assisted referral. The proportion in each region that included at least one recommendation were: 100% AFR (24/47), 100% EMR (6/6), 100% AMR (5/5), 100% WPR (5/5), 100% SEAR (4/4) and 95% EUR (20/21). AFR followed by EMR included the highest number of reccomendations., Conclusion: There was substantial variability in the uptake of the WHO-differentiated HTS recommendations. Those in EMR included the most WHO-differentiated HTS recommendation followed by AFR. Countries within AMR included the least number of recommendations. Ongoing advocacy and efforts are needed to support the uptake of the WHO-differentiated HTS recommendations in country policies as well as their implementation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: In the UK, the number of new HIV diagnoses among gay and bisexual men who have sex with men (GBMSM) has decreased substantially. We aimed to understand the contribution of different interventions in reducing HIV incidence so far; to estimate future HIV incidence with continuation of current policies and with further scaling up of current interventions; and to estimate the maximum additional annual cost that should be spent towards these interventions for them to offer value for money., Methods: We calibrated a dynamic, individual-based, stochastic simulation model, the HIV Synthesis Model, to multiple sources of data on HIV among GBMSM aged 15 years or older in the UK. Primarily these were routine HIV surveillance data collected by the UK Health Security Agency. We compared HIV incidence in 2022 with the counterfactual incidence: if HIV testing rates stopped increasing in 2012 and the policy of antiretroviral therapy (ART) at diagnosis was not introduced in mid-2015; if pre-exposure prophylaxis (PrEP) was not introduced; if condom use was low from 2012 in all GBMSM, at levels similar to those observed in 1980; and in the first and second scenario combined. We also projected future outcomes under the assumption of continuation of current policies and considering increases in PrEP and HIV testing uptake and a decrease in condomless sex., Findings: Our model estimated a 77% (90% uncertainty interval [UI] 61-88) decline in HIV incidence since around 2014, with an estimated 597 infections ([90% UI 312-956]; 1·1 per 1000 person-years [90% UI 0·6-1·8]) in men aged 15-64 years in 2022. Both PrEP introduction and increased HIV testing with ART initiation at diagnosis each had a substantial effect on HIV incidence. Without PrEP introduction, we estimate there would have been 2·16 times the number of infections that actually occurred (90% UI 1·06-3·75) between 2012 and 2022; without increased HIV testing and ART initiation at diagnosis there would have been 2·18 times the number of infections that actually occurred (1·18-3·60), and if condomless sex was at the levels before the HIV epidemic, there would have been 2·27 times the number of infections that actually occurred (0·9-5·4). If rates of testing, ART use, and PrEP use remain as they are currently, there is a predicted decline in incidence to 388 HIV infections in 2025 (90% UI 226-650) and to 263 (137-433) in 2030. Increases in HIV testing and PrEP use were predicted to accelerate the decline in HIV incidence. Given the quality-adjusted life-year (QALY) benefit and a cost-effectiveness threshold of £30 000 per QALY gained, in order to be cost-effective an additional £1·62 million could be spent per year to increase testing levels by 34% (90% UI 25-46) and PrEP use by 55% (10-107). To achieve that, a 16% reduction in the cost of delivery of testing and PrEP would be required., Interpretation: Combination prevention, including a PrEP strategy, played a major role in the reduction in HIV incidence observed so far in the UK among GBMSM. Continuation of current activities should lead to a continued decline; however, it is unlikely to lead to reaching the target of fewer than 50 HIV infections per year among GBMSM by 2030. It will be important to reduce costs for testing and PrEP for their continued expansion to be cost-effective., Funding: National Institute for Health Research under its Programme Grants for Applied Research Programme and Medical Research Council-UK Research and Innovation., Competing Interests: Declaration of interests GC received payment for community advisory board from Gilead Sciences. SM received grants from EDCTP, Imperial College, NIHR, and Magee Women's Research Institute and Foundation (MATRIX). AM is employed by Source HE—a consultancy that provided advice to pharmaceutical companies. VC received funding from Source HE. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Chemsex (the use of psychoactive drugs in sexual contexts) has been associated with HIV acquisition and other STIs, so there is benefit in identifying those most likely to start chemsex to offer risk reduction interventions such as pre-exposure prophylaxis (PrEP). To date, there have been no data from a longitudinal study analysing factors most associated with starting and stopping chemsex., Methods: The prospective cohort study, Attitudes to and Understanding Risk of Acquisition of HIV over Time (AURAH2), collected 4 monthly and annual online questionnaire data from men who have sex with men (MSM) from 2015 to 2018. We investigate the association of sociodemographic factors, sexual behaviours and drug use with starting and stopping chemsex among 622 men who completed at least one follow-up questionnaire. Poisson models with generalised estimating equations were used to produce risk ratios (RRs) accounting for multiple starting or stopping episodes from the same individual. Multivariable analysis was adjusted for age group, ethnicity, sexual identity and university education., Findings: In the multivariable analysis, the under 40 age group was significantly more likely to start chemsex by the next assessment (RR 1.79, 95% CI 1.12 to 2.86). Other factors which showed significant association with starting chemsex were unemployment (RR 2.10, 95% CI 1.02 to 4.35), smoking (RR 2.49, 95% CI 1.63 to 3.79), recent condomless sex (CLS), recent STI and postexposure prophylaxis (PEP) use in the past year (RR 2.10, 95% CI 1.33 to 3.30). Age over 40 (RR 0.71, 95% CI 0.51 to 0.99), CLS, and use of PEP (RR 0.64, 95% CI 0.47 to 0.86) and PrEP (RR 0.47, 95% CI 0.29 to 0.78) were associated with lower likelihood of stopping chemsex by the next assessment., Interpretation: Knowledge of these results allows us to identify men most likely to start chemsex, thus providing an opportunity for sexual health services to intervene with a package of risk mitigation measures, especially PrEP use., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Understanding the health care activity and associated hospital costs of caring for people living with HIV is an important component of assessing the cost effectiveness of new technologies and for budget planning., Methods: Data collected between 2010 and 2017 from an English HIV treatment centre were combined with national reference costs to estimate the rate of hospital attendances and costs per quarter year, according to demographic and clinical factors. The final dataset included records for 1763 people living with HIV, which was analysed using negative binomial regression models and general estimating equations., Results: People living with HIV experienced an unadjusted average of 0.028 (standard deviation [SD] 0.20) inpatient episodes per quarter, equivalent to one every 9 years, and 1.85 (SD 2.30) outpatient visits per quarter. The unadjusted mean quarterly cost per person with HIV (excluding antiretroviral drug costs) was £439 (SD 604). Outpatient appointments and inpatient episodes accounted for 88% and 6% of total costs, respectively. In adjusted models, low CD4 count was the strongest predictor of inpatient stays and outpatient visits. Low CD4 count and new patient status (having a first visit at the Trust in the last 6 months) were the factors that most increased estimated costs. Associations were weaker or less consistent for demographic factors (age, sex/sexual orientation/ethnicity). Sensitivity analyses suggest that the findings were generally robust to alternative parameter and modelling assumptions., Conclusion: A number of factors predicted hospital activity and costs, but CD4 cell count and new patient status were the strongest. The study results can be incorporated into future economic evaluations and budget impact assessments of HIV-related technologies., (© 2023 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Background: Mathematical models are increasingly used to inform HIV policy and planning. Comparing estimates obtained using different mathematical models can test the robustness of estimates and highlight research gaps. As part of a larger project aiming to determine the optimal allocation of funding for HIV services, in this study we compare projections from five mathematical models of the HIV epidemic in South Africa: EMOD-HIV, Goals, HIV-Synthesis, Optima, and Thembisa., Methods: The five modelling groups produced estimates of the total population, HIV incidence, HIV prevalence, proportion of people living with HIV who are diagnosed, ART coverage, proportion of those on ART who are virally suppressed, AIDS-related deaths, total deaths, and the proportion of adult males who are circumcised. Estimates were made under a "status quo" scenario for the period 1990 to 2040. For each output variable we assessed the consistency of model estimates by calculating the coefficient of variation and examining the trend over time., Results: For most outputs there was significant inter-model variability between 1990 and 2005, when limited data was available for calibration, good consistency from 2005 to 2025, and increasing variability towards the end of the projection period. Estimates of HIV incidence, deaths in people living with HIV, and total deaths displayed the largest long-term variability, with standard deviations between 35 and 65% of the cross-model means. Despite this variability, all models predicted a gradual decline in HIV incidence in the long-term. Projections related to the UNAIDS 95-95-95 targets were more consistent, with the coefficients of variation below 0.1 for all groups except children., Conclusions: While models produced consistent estimates for several outputs, there are areas of variability that should be investigated. This is important if projections are to be used in subsequent cost-effectiveness studies., (© 2023. The Author(s).)

Background: Post-exposure prophylaxis (PEP) offers protection from HIV after condomless sex, but is not widely available in a timely manner in east, central, southern, and west Africa. To inform the potential pilot implementation of such an approach, we modelled the effect and cost-effectiveness of making PEP consisting of tenofovir, lamivudine, and dolutegravir (TLD) freely and locally available in communities without prescription, with the aim of enabling PEP use within 24 h of condomless sex. Free community availability of TLD (referred to as community TLD) might also result in some use of TLD as pre-exposure prophylaxis (PrEP) and as antiretroviral therapy for people living with HIV., Methods: Using an existing individual-based model (HIV Synthesis), we explicitly modelled the potential positive and negative effects of community TLD. Through the sampling of parameter values we created 1000 setting-scenarios, reflecting the uncertainty in assumptions and a range of settings similar to those seen in east, central, southern, and west Africa (with a median HIV prevalence of 14·8% in women and 8·1% in men). For each setting scenario, we considered the effects of community TLD. TLD PEP was assumed to have at least 90% efficacy in preventing HIV infection after condomless sex with a person living with HIV., Findings: The modelled effects of community TLD availability based on an assumed high uptake of TLD resulted in a mean reduction in incidence of 31% (90% range over setting scenarios, 6% increase to 57% decrease) over 20 years, with an HIV incidence reduction over 50 years in 91% of the 1000 setting scenarios, deaths averted in 55% of scenarios, reduction in costs in 92% of scenarios, and disability-adjusted life-years averted in 64% of scenarios with community TLD. Community TLD was cost-effective in 90% of setting scenarios and cost-saving (with disability-adjusted life-years averted) in 58% of scenarios. When only examining setting scenarios in which there was lower uptake of community TLD, community TLD is cost-effective in 92% of setting scenarios., Interpretation: The introduction of community TLD, enabling greater PEP access, is a promising approach to consider further in pilot implementation projects., Funding: Bill & Melinda Gates Foundation to the HIV Modelling Consortium., Competing Interests: Declaration of interests ANP reports a research grant from the Bill & Melinda Gates Foundation for the current work; and grants from Wellcome, the National Institutes for Health, and European Commission outside this work. FC reports grants from the Wellcome Trust, the Bill & Melinda Gates Foundation, the Medical Research Council, the National Institute for Mental Health, UNICEF, and UNAIDS to support travel for expert panel meetings; being a board member for UK Research and Innovation Global Health Research Board and African Research Leaders Fellowship Schemes; and being a member on a WHO Expert Panel. LB-M reports a research grant from Bill & Melinda Gates Foundation for the current work. VC reports grants from UK Research Institute, the National Institute for Mental Health, United States Agency for International Development, Medical Research Council, and the Bill & Melinda Gates Foundation. JRH reports grants from the Bill & Melinda Gates Foundation and Wellcome and consulting fees from Gavi. This Article was written by CG in her capacity as a US Government employee, but the views expressed in this paper do not represent those of the Department of State or the Centers for Disease Control and Prevention. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Long-acting injectable cabotegravir pre-exposure prophylaxis (PrEP) is recommended by WHO as an additional option for HIV prevention in sub-Saharan Africa, but there is concern that its introduction could lead to an increase in integrase-inhibitor resistance undermining treatment programmes that rely on dolutegravir. We aimed to project the health benefits and risks of cabotegravir-PrEP introduction in settings in sub-Saharan Africa., Methods: With HIV Synthesis, an individual-based HIV model, we simulated 1000 setting-scenarios reflecting both variability and uncertainty about HIV epidemics in sub-Saharan Africa and compared outcomes for each with and without cabotegravir-PrEP introduction. PrEP use is assumed to be risk-informed and to be used only in 3-month periods (the time step for the model) when having condomless sex. We consider three groups at risk of integrase-inhibitor resistance emergence: people who start cabotegravir-PrEP after (unknowingly) being infected with HIV, those who seroconvert while on PrEP, and those with HIV who have residual cabotegravir drugs concentrations during the early tail period after recently stopping PrEP. We projected the outcomes of policies of cabotegravir-PrEP introduction and of no introduction in 2022 across 50 years. In 50% of setting-scenarios we considered that more sensitive nucleic-acid-based HIV diagnostic testing (NAT), rather than regular antibody-based HIV rapid testing, might be used to reduce resistance risk. For cost-effectiveness analysis we assumed in our base case a cost of cabotegravir-PrEP drug to be similar to oral PrEP, resulting in a total annual cost of USD$144 per year ($114 per year and $264 per year considered in sensitivity analyses), a cost-effectiveness threshold of $500 per disability-adjusted life years averted, and a discount rate of 3% per year., Findings: Reflecting our assumptions on the appeal of cabotegravir-PrEP, its introduction is predicted to lead to a substantial increase in PrEP use with approximately 2·6% of the adult population (and 46% of those with a current indication for PrEP) receiving PrEP compared with 1·5% (28%) without cabotegravir-PrEP introduction across 20 years. As a result, HIV incidence is expected to be lower by 29% (90% range across setting-scenarios 6-52%) across the same period compared with no introduction of cabotegravir-PrEP. In people initiating antiretroviral therapy, the proportion with integrase-inhibitor resistance after 20 years is projected to be 1·7% (0-6·4%) without cabotegravir-PrEP introduction but 13·1% (4·1-30·9%) with. Cabotegravir-PrEP introduction is predicted to lower the proportion of all people on antiretroviral therapy with viral loads less than 1000 copies per mL by 0·9% (-2·5% to 0·3%) at 20 years. For an adult population of 10 million an overall decrease in number of AIDS deaths of about 4540 per year (-13 000 to -300) across 50 years is predicted, with little discernible benefit with NAT when compared with standard antibody-based rapid testing. AIDS deaths are predicted to be averted with cabotegravir-PrEP introduction in 99% of setting-scenarios. Across the 50-year time horizon, overall HIV programme costs are predicted to be similar regardless of whether cabotegravir-PrEP is introduced (total mean discounted annual HIV programme costs per year across 50 years is $151·3 million vs $150·7 million), assuming the use of standard antibody testing. With antibody-based rapid HIV testing, the introduction of cabotegravir-PrEP is predicted to be cost-effective under an assumed threshold of $500 per disability-adjusted life year averted in 82% of setting-scenarios at the cost of $144 per year, in 52% at $264, and in 87% at $114., Interpretation: Despite leading to increases in integrase-inhibitor drug resistance, cabotegravir-PrEP introduction is likely to reduce AIDS deaths in addition to HIV incidence. Long-acting cabotegravir-PrEP is predicted to be cost-effective if delivered at similar cost to oral PrEP with antibody-based rapid HIV testing., Funding: Bill & Melinda Gates Foundation, National Institute of Allergy and Infectious Diseases of the National Institutes of Health., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Voluntary medical male circumcision (VMMC) has been a recommended HIV prevention strategy in sub-Saharan Africa since 2007, particularly in countries with high HIV prevalence. However, given the scale-up of antiretroviral therapy programmes, it is not clear whether VMMC still represents a cost-effective use of scarce HIV programme resources., Methods: Using five existing well described HIV mathematical models, we compared continuation of VMMC for 5 years in men aged 15 years and older to no further VMMC in South Africa, Malawi, and Zimbabwe and across a range of setting scenarios in sub-Saharan Africa. Outputs were based on a 50-year time horizon, VMMC cost was assumed to be US$90, and a cost-effectiveness threshold of US$500 was used., Findings: In South Africa and Malawi, the continuation of VMMC for 5 years resulted in cost savings and health benefits (infections and disability-adjusted life-years averted) according to all models. Of the two models modelling Zimbabwe, the continuation of VMMC for 5 years resulted in cost savings and health benefits by one model but was not as cost-effective according to the other model. Continuation of VMMC was cost-effective in 68% of setting scenarios across sub-Saharan Africa. VMMC was more likely to be cost-effective in modelled settings with higher HIV incidence; VMMC was cost-effective in 62% of settings with HIV incidence of less than 0·1 per 100 person-years in men aged 15-49 years, increasing to 95% with HIV incidence greater than 1·0 per 100 person-years., Interpretation: VMMC remains a cost-effective, often cost-saving, prevention intervention in sub-Saharan Africa for at least the next 5 years., Funding: Bill & Melinda Gates Foundation for the HIV Modelling Consortium., Competing Interests: Declaration of interests LB-M has received support for the present manuscript paid to his institution from the Bill & Melinda Gates Foundation (BMGF). AB has received grants or contracts from the US National Institutes of Health and Foundation for Innovative New Diagnostics (FIND), and consulting fees from Gates Ventures. FMC has received grants or contracts paid to her institution from Wellcome Trust, BMGF, Medical Research Council (MRC), UNICEF, and UNITAID. GM-R has received support for the present manuscript paid to her institution from BMGF, and grants or contracts paid to her institution from National Institutes of Health, FIND, BMGF, and United States Agency for International Development (USAID). MH has received support for the present manuscript paid to his institution from BMGF. KK has received support for the present manuscript paid to her institution from BMGF and a grant from UNAIDS to support modelling activities not directly related to this manuscript. VC has received support for the present manuscript paid to her institution from BMGF and grants paid to her institution from the UK Research and Innovation, UNITAID, National Institute for Health Research, USAID, MRC, and BMGF. VC has received consulting fees from WHO. AP has received support for the present manuscript paid to his institution from BMGF. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: HIV transmission continues among gay and bisexual men who have sex with men (GBMSM), with those who are younger, or recent migrants, or of minority ethnicity or who are gender diverse remaining at increased risk. We aimed to identify and describe recent studies evaluating the effectiveness of HIV prevention interventions for GBMSM in high income countries., Methods: We searched ten electronic databases for randomized controlled trials (RCTs), conducted in high income settings, and published since 2013 to update a previous systematic review (Stromdahl et al, 2015). We predefined four outcome measures of interest: 1) HIV incidence 2) STI incidence 3) condomless anal intercourse (CLAI) (or measure of CLAI) and 4) number of sexual partners. We used the National Institute for Health and Care Excellence (UK) Quality Appraisal of Intervention Studies tool to assess the quality of papers included in the review. As the trials contained a range of effect measures (e.g. odds ratio, risk difference) comparing the arms in the RCTs, we converted them into standardized effect sizes (SES) with 95% confidence intervals (CI)., Results: We identified 39 original papers reporting 37 studies. Five intervention types were identified: one-to-one counselling (15 papers), group interventions (7 papers), online interventions (9 papers), Contingency Management for substance use (2 papers) and Pre-exposure Prophylaxis (PrEP) (6 papers). The quality of the studies was mixed with over a third of studies rated as high quality and 11% rated as poor quality. There was some evidence that one-to-one counselling, group interventions (4-10 participants per group) and online (individual) interventions could be effective for reducing HIV transmission risk behaviours such as condomless anal intercourse. PrEP was the only intervention that was consistently effective at reducing HIV incidence., Conclusions: Our systematic review of the recent evidence that we were able to analyse indicates that PrEP is the most effective intervention for reducing HIV acquisition among GBMSM. Targeted and culturally tailored behavioural interventions for sub-populations of GBMSM vulnerable to HIV infection and other STIs should also be considered, particularly for GBMSM who cannot access or decline to use PrEP., Competing Interests: The authors have declared that no competing interests exist.

Background: In this so-called treat-all era, antiretroviral therapy (ART) interruptions contribute to an increasing proportion of HIV infections and deaths. Many strategies to improve retention on ART cost more than standard of care. In this study, we aimed to estimate the upper-bound costs at which such interventions should be adopted., Methods: In this combined analysis, we compared the infections averted, disability-adjusted life-years (DALYs) averted, and upper-bound costs of interventions that improve ART retention in three HIV models with diverse structures, assumptions, and baseline settings: EMOD in South Africa, Optima in Malawi, and Synthesis in sub-Saharan African low-income and middle-income countries (LMICs). We modelled estimates over a 40-year time horizon, from a baseline of Jan 1, 2022, when interventions would be implemented, to Jan 1, 2062. We varied increment of ART retention (25%, 50%, 75%, and 100% retention), the extent to which interventions could be targeted towards individuals at risk of interrupting ART, and cost-effectiveness thresholds in each setting., Findings: Despite simulating different settings and epidemic trends, all three models produced consistent estimates of health benefit (ie, DALYs averted) and transmission reduction per increment in retention. The range of estimates was 1·35-3·55 DALYs and 0·12-0·20 infections averted over the 40-year time horizon per additional person-year retained on ART. Upper-bound costs varied by setting and intervention effectiveness. Improving retention by 25% among all people receiving ART, regardless of risk of ART interruption, gave an upper-bound cost per person-year of US$2-6 in Optima (Malawi), $43-68 in Synthesis (LMICs in sub-Saharan Africa), and $28-180 in EMOD (South Africa). A maximally targeted and effective retention intervention had an upper-bound cost per person-year of US$93-223 in Optima (Malawi), $871-1389 in Synthesis (LMICs in sub-Saharan Africa), and $1013-6518 in EMOD (South Africa)., Interpretation: Upper-bound costs that could improve ART retention vary across sub-Saharan African settings and are likely to be similar to or higher than was estimated before the start of the treat-all era. Upper-bound costs could be increased by targeting interventions to those most at risk of interrupting ART., Funding: Bill & Melinda Gates Foundation., Competing Interests: Declaration of interests Unless otherwise stated, all authors are salaried employees of the institutions to which they are affiliated in the header. AB declares grants from the Bill & Melinda Gates Foundation (BMGF) and the US National Institutes of Health (NIH). LJ declares grants from the United States Agency for International Development (USAID) and BMGF. ANP declares grants from NIH, UK Research and Innovation (UKRI), Wellcome Trust, and BMGF and payment for serving on the HIV Glasgow Congress steering committee. VC declares grants from UKRI, Unitaid, National Institute for Health Research, USAID, UK Research and Innovation Medical Research Council, and BMGF and consulting fees from WHO. GM-R declares grants from BMGF, USAID South Africa, USAID, and Foundation for Innovative New Diagnostics and serving in leadership or fiduciary roles at the WHO, South African Department of Health, and South African National AIDS Council. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Road traffic injuries are a significant cause of death and disability globally. However, in some countries the exact health burden caused by road traffic injuries is unknown. In Malawi, there is no central reporting mechanism for road traffic injuries and so the exact extent of the health burden caused by road traffic injuries is hard to determine. A limited number of models predict the incidence of mortality due to road traffic injury in Malawi. These estimates vary greatly, owing to differences in assumptions, and so the health burden caused on the population by road traffic injuries remains unclear., Methods: We use an individual-based model and combine an epidemiological model of road traffic injuries with a health seeking behaviour and health system model. We provide a detailed representation of road traffic injuries in Malawi, from the onset of the injury through to the final health outcome. We also investigate the effects of an assumption made by other models that multiple injuries do not contribute to health burden caused by road accidents., Results: Our model estimates an overall average incidence of mortality between 23.5 and 29.8 per 100,000 person years due to road traffic injuries and an average of 180,000 to 225,000 disability-adjusted life years (DALYs) per year between 2010 and 2020 in an estimated average population size of 1,364,000 over the 10-year period. Our estimated incidence of mortality falls within the range of other estimates currently available for Malawi, whereas our estimated number of DALYs is greater than the only other estimate available for Malawi, the GBD estimate predicting and average of 126,200 DALYs per year over the same time period. Our estimates, which account for multiple injuries, predict a 22-58% increase in overall health burden compared to the model ran as a single injury model., Conclusions: Road traffic injuries are difficult to model with conventional modelling methods, owing to the numerous types of injuries that occur. Using an individual-based model framework, we can provide a detailed representation of road traffic injuries. Our results indicate a higher health burden caused by road traffic injuries than previously estimated., (© 2022. The Author(s).)

Introduction: Young female sex workers (FSW) are disproportionately vulnerable to HIV. Zimbabwe data show higher HIV incidence and lower engagement in services compared to older FSW. Utilizing data from a combination HIV prevention and treatment intervention, we describe engagement in the HIV services over time among FSW 18-24 years, compared to those ≥25 years of age., Materials and Methods: Data were collected via respondent-driven sampling (RDS) surveys in 14 communities in 2013 and 2016, with >2500 FSW per survey. They included blood samples for HIV and viral load testing. As the intervention had no significant impact on HIV care cascade outcomes, data were aggregated across study arms. Analyses used RDS-II estimation., Results: Mean age in 2013 and 2016 was 31 and 33 years, with 27% and 17% aged 18-24 years. Overall HIV prevalence was 59% at each timepoint, and 35% and 36% among younger FSW. From 2013 to 2016 there was an increase in young HIV-positive FSW knowing their status (38% vs 60%, OR = 2.51, p<0.01). Outcomes for all FSW improved significantly over time at all steps of the cascade, and the relative change over time was similar among older versus younger FSW for most cascade variables., Discussion: Young FSW had improvements in care cascade outcomes, and proportionate improvements similar to older FSW, yet they remain less engaged in services overall. This implies that the dedicated FSW services in Zimbabwe are having a comparably positive impact across age groups, however more is likely required to address young FSW's unique vulnerabilities and needs., Competing Interests: The authors have declared that no competing interests exist.

Background: Approaches that allow easy access to pre-exposure prophylaxis (PrEP), such as over-the-counter provision at pharmacies, could facilitate risk-informed PrEP use and lead to lower HIV incidence, but their cost-effectiveness is unknown. We aimed to evaluate conditions under which risk-informed PrEP use is cost-effective., Methods: We applied a mathematical model of HIV transmission to simulate 3000 setting-scenarios reflecting a range of epidemiological characteristics of communities in sub-Saharan Africa. The prevalence of HIV viral load greater than 1000 copies per mL among all adults (HIV positive and negative) varied from 1·1% to 7·4% (90% range). We hypothesised that if PrEP was made easily available without restriction and with education regarding its use, women and men would use PrEP, with sufficient daily adherence, during so-called seasons of risk (ie, periods in which individuals are at risk of acquiring infection). We refer to this as risk-informed PrEP. For each setting-scenario, we considered the situation in mid-2021 and performed a pairwise comparison of the outcomes of two policies: immediate PrEP scale-up and then continuation for 50 years, and no PrEP. We estimated the relationship between epidemic and programme characteristics and cost-effectiveness of PrEP availability to all during seasons of risk. For our base-case analysis, we assumed a 3-monthly PrEP cost of US$29 (drug $11, HIV test $4, and $14 for additional costs necessary to facilitate education and access), a cost-effectiveness threshold of $500 per disability-adjusted life-year (DALY) averted, an annual discount rate of 3%, and a time horizon of 50 years. In sensitivity analyses, we considered a cost-effectiveness threshold of $100 per DALY averted, a discount rate of 7% per annum, the use of PrEP outside of seasons of risk, and reduced uptake of risk-informed PrEP., Findings: In the context of PrEP scale-up such that 66% (90% range across setting-scenarios 46-81) of HIV-negative people with at least one non-primary condomless sex partner take PrEP in any given period, resulting in 2·6% (0·9-6·0) of all HIV negative adults taking PrEP at any given time, risk-informed PrEP was predicted to reduce HIV incidence by 49% (23-78) over 50 years compared with no PrEP. PrEP was cost-effective in 71% of all setting-scenarios, and cost-effective in 76% of setting-scenarios with prevalence of HIV viral load greater than 1000 copies per mL among all adults higher than 2%. In sensitivity analyses with a $100 per DALY averted cost-effectiveness threshold, a 7% per year discount rate, or with PrEP use that was less well risk-informed than in our base case, PrEP was less likely to be cost-effective, but generally remained cost-effective if the prevalence of HIV viral load greater than 1000 copies per mL among all adults was higher than 3%. In sensitivity analyses based on additional setting-scenarios in which risk-informed PrEP was less extensively used, the HIV incidence reduction was smaller, but the cost-effectiveness of risk-informed PrEP was undiminished., Interpretation: Under the assumption that making PrEP easily accessible for all adults in sub-Saharan Africa in the context of community education leads to risk-informed use, PrEP is likely to be cost-effective in settings with prevalence of HIV viral load greater than 1000 copies per mL among all adults higher than 2%, suggesting the need for implementation of such approaches, with ongoing evaluation., Funding: US Agency for International Development, US President's Emergency Plan for AIDS Relief, and Bill & Melinda Gates Foundation., Competing Interests: Declaration of interests Unless otherwise stated, all authors are salaried employees of the institutions to which they are affiliated in the header. JWM declares grants from the National Institutes of Health (NIH), US Agency for International Development (USAID), Gilead Sciences, and Janssen Pharmaceuticals Research to the University of Pittsburgh; consulting fees from Gilead Sciences; shares with Abound Bio; and share options with Infectious Diseases Connect. VC reports research grants from UK Research and Innovation (UKRI), Unitaid, National Institute for Health Research, USAID, Medical Research Council (MRC), and Bill & Melinda Gates Foundation; and consulting fees from WHO. TBH declares research grants to their institution from Bill & Melinda Gates Foundation, WHO, UNAIDS, NIH, MRC, and Department for International Development/Foreign, Commonwealth and Development Office; and consulting fees from WHO, Global Fund to Fight AIDS, Tuberculosis and Malaria, and Gilead. ANP declares research grants from UKRI, Wellcome Trust, USAID, NIH, and Bill & Melinda Gates Foundation; and consulting fees from Bill & Melinda Gates Foundation. All other authors declare no competing interests., (Copyright © 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Prospective cohort studies of incident HIV and associated factors among gay, bisexual, and other men who have sex with men (GBMSM) in the United Kingdom are lacking. We report time trends in and factors associated with HIV incidence between 2013 and 2019 among a cohort of GBMSM: the AURAH2 prospective study., Methods and Findings: Participants were recruited through 1 of 3 sexual health clinics in London and Brighton (July 2013 to April 2016) and self-completed a baseline paper questionnaire and subsequent 4-monthly and annual online questionnaires (March 2015 to March 2018), including information on sociodemographics, lifestyle, health and well-being, HIV status, sexual/HIV-related behaviours, and preexposure prophylaxis and postexposure prophylaxis (PrEP/PEP). Incident HIV was ascertained by linkage with national HIV surveillance data from Public Health England (PHE). We investigated the associations of HIV incidence with (1) baseline factors using mixed-effects Weibull proportional hazard models, unadjusted and adjusted for age, country of birth and ethnicity, sexuality, and education level; and (2) time-updated factors, using mixed-effects Poisson regression models. In total, 1,162 men (mean age 34 years, 82% white, 94% gay, 74% university-educated) were enrolled in the study. Thirty-three HIV seroconversions occurred over 4,618.9 person-years (PY) of follow-up: an overall HIV incidence rate (IR) of 0.71 (95% confidence interval (CI) 0.51 to 1.00) per 100 PY. Incidence declined from 1.47 (95% CI 0.48 to 4.57) per 100 PY in 2013/2014 to 0.25 (95% CI 0.08 to 0.78) per 100 PY in 2018/2019; average annual decline was 0.85-fold (p < 0.001). Baseline factors associated with HIV acquisition included the following: injection drug use (6/38 men who reported injection drug-acquired HIV; unadjusted conditional hazard ratio (HR) 27.96, 95% CI 6.99 to 111.85, p < 0.001), noninjection chemsex-related drug use (13/321; HR 6.45, 95% CI 1.84 to 22.64, p < 0.001), condomless anal sex (CLS) (26/741; HR 3.75, 95% CI 1.31 to 10·74, p = 0.014); higher number of CLS partners (HRs >10 partners [7/57]; 5 to 10 partners [5/60]; and 2 to 4 partners [11/293]: 14.04, 95% CI 4.11 to 47.98; 9.60, 95% CI 2.58 to 35.76; and 4.05, 95% CI 1.29 to 12.72, respectively, p < 0.001); CLS with HIV-positive partners (14/147; HR 6.45, 95% CI 3.15 to 13.22, p < 0.001), versatile CLS role (21/362; HR 6.35, 95% CI 2.18 to 18.51, p < 0.001), group sex (64/500; HR 8.81, 95% CI 3.07 to 25.24, p < 0.001), sex for drugs/money (4/55, HR 3.27, 95% CI 1.14 to 9.38, p = 0.027) (all in previous 3 months); previous 12-month report of a bacterial sexually transmitted infection (STI) diagnoses (21/440; HR 3.95, 95% CI 1.81 to 8.63, p < 0.001), and more than 10 new sexual partners (21/471, HRs 11 to 49, 50 to 99, and >100 new partners: 3.17, 95% CI 1.39 to 7.26; 4.40, 95% CI 1.35 to 14.29; and 4.84, 95% CI 1.05 to 22.4, respectively, p < 0.001). Results were broadly consistent for time-updated analysis (n = 622 men). The study's main limitation is that men may not be representative of the broader GBMSM population in England., Conclusions: We observed a substantial decline in HIV incidence from 2013 to 2019 among GBMSM attending sexual health clinics. Injection drug use, chemsex use, and measures of high-risk sexual behaviour were strongly associated with incident HIV. Progress towards zero new infections could be achieved if combination HIV prevention including Test and Treat strategies and routine commissioning of a PrEP programme continues across the UK and reaches all at-risk populations., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: AC reports personal fees from Gilead Sciences for advisory board attendance & conference sponsorship, personal fees from ViiV for advisory board attendance, outside the submitted work. FCL reports grants from National Institute for Health Research (NIHR) during the conduct of the study. NN has been a full-time employee of ViiV Healthcare since March 2019 and reports personal fees, and support for conference attendance from ViiV Healthcare, and Gilead Sciences outside the submitted work. All other authors have declared that no competing interests exist.

Introduction: Oral preexposure prophylaxis (PrEP) in the form of tenofovir-disoproxil-fumarate/emtricitabine is being implemented in selected sites in South Africa. Addressing outstanding questions on PrEP cost-effectiveness can inform further implementation., Methods: We calibrated an individual-based model to KwaZulu-Natal to predict the impact and cost-effectiveness of PrEP, with use concentrated in periods of condomless sex, accounting for effects on drug resistance. We consider (1) PrEP availability for adolescent girls and young women aged 15-24 years and female sex workers, and (2) availability for everyone aged 15-64 years. Our primary analysis represents a level of PrEP use hypothesized to be attainable by future PrEP programs., Results: In the context of PrEP use in adults aged 15-64 years, there was a predicted 33% reduction in incidence and 36% reduction in women aged 15-24 years. PrEP was cost-effective, including in a range of sensitivity analyses, although with substantially reduced (cost) effectiveness under a policy of ART initiation with efavirenz- rather than dolutegravir-based regimens due to PrEP undermining ART effectiveness by increasing HIV drug resistance., Conclusions: PrEP use concentrated during time periods of condomless sex has the potential to substantively impact HIV incidence and be cost-effective., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Since October, 2017 (and until October, 2020), pre-exposure prophylaxis (PrEP) has only been available in England, UK, through the PrEP Impact Trial, by purchasing it from some genitourinary medicine clinics, or via online sources. Here we report changes from 2013 to 2018 in PrEP and postexposure prophylaxis (PEP) awareness and use among HIV-negative gay, bisexual, and other men who have sex with men (MSM) and assess predictors of PrEP initiation., Methods: In the prospective cohort study Attitudes to, and Understanding of Risk of Acquisition of HIV 2 (AURAH2), MSM were recruited from three sexual health clinics in England: two in London and one in Brighton, UK. Men were eligible if they were aged 18 years or older and HIV-negative or of unknown HIV status. Participants self-completed a baseline paper questionnaire at one of the three clinics between July 30, 2013, and April 30, 2016, and were subsequently able to complete 4-monthly and annual online questionnaires, which were available between March 1, 2015, and March 31, 2018, and collected information on sociodemographics, health and wellbeing, HIV status, and sexual behaviours. PrEP and PEP use in the previous 12 months was obtained at baseline and in annual questionnaires. We assessed trends over calendar time in 3-month periods from first enrolment to the end of the study period (July-December, 2013, was counted as one period) in use of PrEP and PEP using generalised estimating equation logistic models. We used age-adjusted Poisson models to assess factors associated with PrEP initiation among participants who reported never having used PrEP at baseline., Findings: 1162 men completed a baseline questionnaire, among whom the mean age was 34 years (SD 10·4), and of those with available data, 942 (82%) of 1150 were white, 1076 (94%) of 1150 were gay, and 857 (74%) of 1159 were university educated. 622 (54%) of 1162 men completed at least one follow-up online questionnaire, of whom 483 (78%) completed at least one annual questionnaire. Overall, PrEP use in the past year increased from 0% (none of 28 respondents) in July to December, 2013, to 43% (23 of 53) in January to March, 2018. The corresponding increase in PrEP use among men who reported condomless sex with two or more partners was from 0% (none of 13 respondents) to 78% (21 of 27). PEP use peaked in April to June, 2016, at 28% (41 of 147 respondents), but decreased thereafter to 8% (four of 53) in January to March, 2018. Among 460 men who had never used PrEP at baseline, predictors of initiating PrEP included age 40-44 years (incidence rate ratio [IRR] 4·25, 95% CI 1·14-15·79) and 45 years and older (3·59, 1·08-11·97) versus younger than 25 years; and after adjustment for age, recent HIV test (5·17, 1·89-14·08), condomless sex (5·01, 2·16-11·63), condomless sex with two or more partners (5·43, 2·99-9·86), group sex (1·69, 1·01-2·84), and non-injection chemsex-related drugs use (2·86, 1·67-4·91) in the past 3 months, PEP use (4·69, 2·83-7·79) in the past 12 months, and calendar year (Jan 1, 2017, to March 31, 2018 vs July 30, 2013, to Dec 31, 2015: 21·19, 9·48-47·35). Non-employment (0·35, 0·14-0·91) and unstable or no housing (vs homeowner 0·13, 0·02-0·95) were associated with reduced rates of PrEP initiation after adjustment for age. About half of PrEP was obtained via the internet, even after the PrEP Impact trial had started (11 [48%] of 23 respondents in January to March, 2018)., Interpretation: PrEP awareness and use increased substantially from 2013 to 2018 among a cohort of MSM in England. Improving access to PrEP by routine commissioning by National Health Service England could increase PrEP use among all eligible MSM, but should include public health strategies to target socioeconomic and demographic disparities in knowledge and use of PrEP., Funding: National Institute for Health Research., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: The integrase inhibitor dolutegravir is being considered in several countries in sub-Saharan Africa instead of efavirenz for people initiating antiretroviral therapy (ART) because of superior tolerability and a lower risk of resistance emergence. WHO requested updated modelling results for its 2019 Antiretroviral Guidelines update, which was restricted to the choice of dolutegravir or efavirenz in new ART initiators. In response to this request, we modelled the risks and benefits of alternative policies for initial first-line ART regimens., Methods: We updated an existing individual-based model of HIV transmission and progression in adults to consider information on the risk of neural tube defects in women taking dolutegravir at time of conception, as well as the effects of dolutegravir on weight gain. The model accounted for drug resistance in determining viral suppression, with consequences for clinical outcomes and mother-to-child transmission. We sampled distributions of parameters to create various epidemic setting scenarios, which reflected the diversity of epidemic and programmatic situations in sub-Saharan Africa. For each setting scenario, we considered the situation in 2018 and compared ART initiation policies of an efavirenz-based regimen in women intending pregnancy, and a dolutegravir-based regimen in others, and a dolutegravir-based regimen, including in women intending pregnancy. We considered predicted outcomes over a 20-year period from 2019 to 2039, used a 3% discount rate, and a cost-effectiveness threshold of US$500 per disability-adjusted life-year (DALY) averted., Findings: Considering updated information on risks and benefits, a policy of ART initiation with a dolutegravir-based regimen rather than an efavirenz-based regimen, including in women intending pregnancy, is predicted to bring population health benefits (10 990 DALYs averted per year) and to be cost-saving (by $2·9 million per year), leading to a reduction in the overall population burden of disease of 16 735 net DALYs per year for a country with an adult population size of 10 million. The policy involving ART initiation with a dolutegravir-based regimen in women intending pregnancy was cost-effective in 87% of our setting scenarios and this finding was robust in various sensitivity analyses, including around the potential negative effects of weight gain., Interpretation: In the context of a range of modelled setting scenarios in sub-Saharan Africa, we found that a policy of ART initiation with a dolutegravir-based regimen, including in women intending pregnancy, was predicted to bring population health benefits and be cost-effective, supporting WHO's strong recommendation for dolutegravir as a preferred drug for ART initiators., Funding: Bill & Melinda Gates Foundation., (Copyright © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Many individuals failing first-line antiretroviral therapy (ART) in sub-Saharan Africa never initiate second-line ART or do so after significant delay. For people on ART with a viral load more than 1000 copies/ml, the WHO recommends a second viral load measurement 3 months after the first viral load and enhanced adherence support. Switch to a second-line regimen is contingent upon a persistently elevated viral load more than 1000 copies/ml. Delayed second-line switch places patients at increased risk for opportunistic infections and mortality., Methods: To assess the potential benefits of a simplified second-line ART switch strategy, we use an individual-based model of HIV transmission, progression and the effect of ART which incorporates consideration of adherence and drug resistance, to compare predicted outcomes of two policies, defining first-line regimen failure for patients on efavirenz-based ART as either two consecutive viral load values more than 1000 copies/ml, with the second after an enhanced adherence intervention (implemented as per current WHO guidelines) or a single viral load value more than 1000 copies/ml. We simulated a range of setting-scenarios reflecting the breadth of the sub-Saharan African HIV epidemic, taking into account potential delays in defining failure and switch to second-line ART., Findings: The use of a single viral load more than 1000 copies/ml to define ART failure would lead to a higher proportion of persons with nonnucleoside reverse-transcriptase inhibitor resistance switched to second-line ART [65 vs. 48%; difference 17% (90% range 14-20%)], resulting in a median 18% reduction in the rate of AIDS-related death over setting scenarios (90% range 6-30%; from a median of 3.1 to 2.5 per 100 person-years) over 3 years. The simplified strategy also is predicted to reduce the rate of AIDS conditions by a median of 31% (90% range 8-49%) among people on first-line ART with a viral load more than 1000 copies/ml in the past 6 months. For a country of 10 million adults (and a median of 880 000 people with HIV), we estimate that this approach would lead to a median of 1322 (90% range 67-3513) AIDS deaths averted per year over 3 years. For South Africa this would represent around 10 215 deaths averted annually., Interpretation: As a step towards reducing unnecessary mortality associated with delayed second-line ART switch, defining failure of first-line efavirenz-based regimens as a single viral load more than 1000 copies/ml should be considered.

Introduction: UNAIDS' goal of ending AIDS by 2030 is unreachable without better targeting of testing, prevention and care. Female sex workers (FSW) in Zimbabwe are at high risk of HIV acquisition and transmission. Here, we report on collated programme and research data from Zimbabwe's national sex work programme. We also assess the potential for wider population impact of FSW programmes by modelling the impact on HIV incidence of eliminating transmission through FSW (i.e. calculate the population attributable fraction of incidence attributable to sex work)., Methods: Descriptive analyses of individual-level programme data collected from FSW between 2009 and June 2018 are triangulated with data collected through 37 respondent driven sampling surveys from 19 sites in Zimbabwe 2011 to 2017. We describe programme coverage, uptake, retention and patterns of sex work behaviour and gaps in service provision. An individual-level stochastic simulation model is used to reconstruct the epidemic and then the incidence compared with the counter-factual trend in incidence from 2010 had transmission through sex work been eliminated from that date., Results: Sisters has reached >67,000 FSW since 2009, increasing attendance as number of sites, programme staff and peer educators were increased. Over 57% of all FSW estimated to be working in Zimbabwe in 2017 (n = 40,000) attended the programme at least once. The proportion of young FSW reached has increased with introduction of the "Young Sisters programme." There are no clear differences in pattern of sex work across settings. Almost all women report condom use with clients at last sex (95%); however, consistent condom use with clients in the last month varies from 52% to 95% by site. Knowledge of HIV-positive status has increased from 48 to 78% between 2011 and 2016, as has prevalence of ART use among diagnosed women (29 to 67%). Although subject to uncertainty, modelling suggests that 70% (90% range: 32%, 93%) of all new infections in Zimbabwe from 2010 are directly or indirectly attributable to transmission via sex work., Conclusions: It is feasible to increase coverage and impact of sex work programming through community-led scale-up of evidence-based interventions. Eliminating transmission through commercial sex would likely have a substantial impact on new infections occurring more widely across Zimbabwe., (© 2019 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Introduction: As prevalence of undiagnosed HIV declines, it is unclear whether testing programmes will be cost-effective. To guide their HIV testing programmes, countries require appropriate metrics that can be measured. The cost-per-diagnosis is potentially a useful metric., Methods: We simulated a series of setting-scenarios for adult HIV epidemics and ART programmes typical of settings in southern Africa using an individual-based model and projected forward from 2018 under two policies: (i) a minimum package of "core" testing (i.e. testing in pregnant women, for diagnosis of symptoms, in sex workers, and in men coming forward for circumcision) is conducted, and (ii) core-testing as above plus additional testing beyond this ("additional-testing"), for which we specify different rates of testing and various degrees to which those with HIV are more likely to test than those without HIV. We also considered a plausible range of unit test costs. The aim was to assess the relationship between cost-per-diagnosis and the incremental cost-effectiveness ratio (ICER) of the additional-testing policy. The discount rate used in the base case was 3% per annum (costs in 2018 U.S. dollars)., Results: There was a strong graded relationship between the cost-per-diagnosis and the ICER. Overall, the ICER was below $500 per-DALY-averted (the cost-effectiveness threshold used in primary analysis) so long as the cost-per-diagnosis was below $315. This threshold cost-per-diagnosis was similar according to epidemic and programmatic features including the prevalence of undiagnosed HIV, the HIV incidence and a measure of HIV programme quality (the proportion of HIV diagnosed people having a viral load <1000 copies/mL). However, restricting to women, additional-testing did not appear cost-effective even at a cost-per-diagnosis of below $50, while restricting to men additional-testing was cost-effective up to a cost-per-diagnosis of $585. The threshold cost per diagnosis for testing in men to be cost-effective fell to $256 when the cost-effectiveness threshold was $300 instead of $500, and to $81 when considering a discount rate of 10% per annum., Conclusions: For testing programmes in low-income settings in southern African there is an extremely strong relationship between the cost-per-diagnosis and the cost-per-DALY averted, indicating that the cost-per-diagnosis can be used to monitor the cost-effectiveness of testing programmes., (© 2019 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Background: The level of evidence for HIV transmission risk through condomless sex in serodifferent gay couples with the HIV-positive partner taking virally suppressive antiretroviral therapy (ART) is limited compared with the evidence available for transmission risk in heterosexual couples. The aim of the second phase of the PARTNER study (PARTNER2) was to provide precise estimates of transmission risk in gay serodifferent partnerships., Methods: The PARTNER study was a prospective observational study done at 75 sites in 14 European countries. The first phase of the study (PARTNER1; Sept 15, 2010, to May 31, 2014) recruited and followed up both heterosexual and gay serodifferent couples (HIV-positive partner taking suppressive ART) who reported condomless sex, whereas the PARTNER2 extension (to April 30, 2018) recruited and followed up gay couples only. At study visits, data collection included sexual behaviour questionnaires, HIV testing (HIV-negative partner), and HIV-1 viral load testing (HIV-positive partner). If a seroconversion occurred in the HIV-negative partner, anonymised phylogenetic analysis was done to compare HIV-1 pol and env sequences in both partners to identify linked transmissions. Couple-years of follow-up were eligible for inclusion if condomless sex was reported, use of pre-exposure prophylaxis or post-exposure prophylaxis was not reported by the HIV-negative partner, and the HIV-positive partner was virally suppressed (plasma HIV-1 RNA <200 copies per mL) at the most recent visit (within the past year). Incidence rate of HIV transmission was calculated as the number of phylogenetically linked HIV infections that occurred during eligible couple-years of follow-up divided by eligible couple-years of follow-up. Two-sided 95% CIs for the incidence rate of transmission were calculated using exact Poisson methods., Findings: Between Sept 15, 2010, and July 31, 2017, 972 gay couples were enrolled, of which 782 provided 1593 eligible couple-years of follow-up with a median follow-up of 2·0 years (IQR 1·1-3·5). At baseline, median age for HIV-positive partners was 40 years (IQR 33-46) and couples reported condomless sex for a median of 1·0 years (IQR 0·4-2·9). During eligible couple-years of follow-up, couples reported condomless anal sex a total of 76 088 times. 288 (37%) of 777 HIV-negative men reported condomless sex with other partners. 15 new HIV infections occurred during eligible couple-years of follow-up, but none were phylogenetically linked within-couple transmissions, resulting in an HIV transmission rate of zero (upper 95% CI 0·23 per 100 couple-years of follow-up)., Interpretation: Our results provide a similar level of evidence on viral suppression and HIV transmission risk for gay men to that previously generated for heterosexual couples and suggest that the risk of HIV transmission in gay couples through condomless sex when HIV viral load is suppressed is effectively zero. Our findings support the message of the U=U (undetectable equals untransmittable) campaign, and the benefits of early testing and treatment for HIV., Funding: National Institute for Health Research., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Recent evidence has suggested that chemsex (the use of mephedrone, crystal methamphetamine and γ -hydroxybutyrate/ γ -butryolactone (GHB/GBL) to enable, enhance and prolong sexual interactions) has increased among men having sex with men (MSM) attending sexual health clinics in large UK cities. To date there has been no data from the UK or Europe that describes changes in chemsex over time within a cohort of MSM., Methods: The prospective cohort study, Attitudes to and Understanding Risk of Acquisition of HIV over Time (AURAH2), collected online questionnaire data from HIV negative or undiagnosed MSM (at enrolment) from 2015 to 2018, recruited from sexual health clinics. We aim to investigate changes in chemsex, three individual drugs associated with chemsex, frequency of chemsex sessions and measures of sexual behaviour, among the cohort of MSM over the study's 3 year follow-up period., Results: In total 622 MSM completed at least one online questionnaire for the AURAH2 study, of which 400 (64.3%) were still engaged with the study within the last six months of follow-up. Prevalence of chemsex significantly declined during the follow-up from 31.8% (198/622) at the first online questionnaire, to 11.1% (8/72; p < 0.001) at the 9th. This decline was reflected in the proportion of MSM reporting use of two of the three individual chemsex drugs: mephedrone use had significantly declined from 25.2% at the first online questionnaire to 9.7% (p < 0.001) at the 9th, GHB/GBL use had also declined from 19.9% to 8.3% (p = 0.001). While crystal methamphetamine use declined, but not significantly (11.1%-6.9% [p = 0.289]). Most measures of sexual behaviour (any anal sex, group sex, recent HIV test and bacterial STI) also tended to decline over the follow-up period, with the exception of CLAI with more than one and more than two partners., Conclusions: Chemsex and use of two individual chemsex drugs (mephedrone and GHB/GBL) significantly declined over time among individuals in the study, alongside most measures of sexual behaviour with the exception of those related to CLAI. Focusing health promotion and HIV prevention, such as awareness of post-exposure prophylaxis (PEP) and access to pre-exposure prophylaxis (PrEP), on MSM that report chemsex, and in particular problematic chemsex, would be highly beneficial, potentially only necessary for a relatively short period of time for individuals, and could have long term benefits for HIV and STI prevention., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: "HIV prevention cascades" have been proposed to support programs by identifying gaps in demand for, access to, and capability to adhere to HIV prevention tools, but there are few empirical examples to guide development. We apply a prevention cascade framework to examine prevention coverage and factors associated with condoms and/or PrEP adherence among female sex workers., Setting: Seven sites across Zimbabwe., Methods: Seven respondent-driven sampling surveys from the intervention sites of a pragmatic cluster-randomized trial in Zimbabwe in 2016 were analyzed, and 611/1439 women testing HIV-negative included. We operationalized key components of an HIV prevention cascade including demand, supply, and capability to adhere to 2 tools for HIV prevention: condoms and pre-exposure prophylaxis (PrEP). We used adjusted logistic regression to identify determinants of adherence to condoms and PrEP in turn, examining the effect of adherence to one tool on adherence to the other., Results: There were 343/611, 54.7%, women reporting adherence to condoms and/or PrEP, leaving almost half uncovered. Although women were aware that condoms prevented HIV and reported good access to them, only 45·5% reported full adherence to condom use. For PrEP, a new technology, there were gaps along all 3 domains of demand, supply, and adherence. Alcohol use decreased adherence to PrEP and condoms. Younger and newer entrants to sex work were less likely to take PrEP every day., Conclusions: HIV prevention programming among female sex workers in Zimbabwe could consider increasing awareness of PrEP alongside supply, alcohol use interventions, and approaches to engaging younger women.

Background: In the UK, approximately 4,200 men who have sex with men (MSM) are living with HIV but remain undiagnosed. Maximising the number of high-risk people testing for HIV is key to ensuring prompt treatment and preventing onward infection. This study assessed how different HIV test characteristics affect the choice of testing option, including remote testing (HIV self-testing or HIV self-sampling), in the UK, a country with universal access to healthcare., Methods and Findings: Between 3 April and 11 May 2017, a cross-sectional online-questionnaire-based discrete choice experiment (DCE) was conducted in which respondents who expressed an interest in online material used by MSM were asked to imagine that they were at risk of HIV infection and to choose between different hypothetical HIV testing options, including the option not to test. A variety of different testing options with different defining characteristics were described so that the independent preference for each characteristic could be valued. The characteristics included where each test is taken, the sampling method, how the test is obtained, whether infections other than HIV are tested for, test accuracy, the cost of the test, the infection window period, and how long it takes to receive the test result. Participants were recruited and completed the instrument online, in order to include those not currently engaged with healthcare services. The main analysis was conducted using a latent class model (LCM), with results displayed as odds ratios (ORs) and probabilities. The ORs indicate the strength of preference for one characteristic relative to another (base) characteristic. In total, 620 respondents answered the DCE questions. Most respondents reported that they were white (93%) and were either gay or bisexual (99%). The LCM showed that there were 2 classes within the respondent sample that appeared to have different preferences for the testing options. The first group, which was likely to contain 86% of respondents, had a strong preference for face-to-face tests by healthcare professionals (HCPs) compared to remote testing (OR 6.4; 95% CI 5.6, 7.4) and viewed not testing as less preferable than remote testing (OR 0.10; 95% CI 0.09, 0.11). In the second group, which was likely to include 14% of participants, not testing was viewed as less desirable than remote testing (OR 0.56; 95% CI 0.53, 0.59) as were tests by HCPs compared to remote testing (OR 0.23; 95% CI 0.15, 0.36). In both classes, free remote tests instead of each test costing £30 was the test characteristic with the largest impact on the choice of testing option. Participants in the second group were more likely to have never previously tested and to be non-white than participants in the first group. The main study limitations were that the sample was recruited solely via social media, the study advert was viewed only by people expressing an interest in online material used by MSM, and the choices in the experiment were hypothetical rather than observed in the real world., Conclusions: Our results suggest that preferences in the context we examined are broadly dichotomous. One group, containing the majority of MSM, appears comfortable testing for HIV but prefers face-to-face testing by HCPs rather than remote testing. The other group is much smaller, but contains MSM who are more likely to be at high infection risk. For these people, the availability of remote testing has the potential to significantly increase net testing rates, particularly if provided for free., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Strategies employing a single rapid diagnostic test (RDT) such as HIV self-testing (HIVST) or "test for triage" (T4T) are proposed to increase HIV testing programme impact. Current guidelines recommend serial testing with two or three RDTs for HIV diagnosis, followed by retesting with the same algorithm to verify HIV-positive status before anti-retroviral therapy (ART) initiation. We investigated whether clients presenting to HIV testing services (HTS) following a single reactive RDT must undergo the diagnostic algorithm twice to diagnose and verify HIV-positive status, or whether a diagnosis with the setting-specific algorithm is adequate for ART initiation., Methods: We calculated (1) expected number of false-positive (FP) misclassifications per 10,000 HIV negative persons tested, (2) positive predictive value (PPV) of the overall HIV testing strategy compared to the WHO recommended PPV ≥99%, and (3) expected cost per FP misclassified person identified by additional verification testing in a typical low-/middle-income setting, compared to the expected lifetime ART cost of $3000. Scenarios considered were as follows: 10% prevalence using two serial RDTs for diagnosis, 1% prevalence using three serial RDTs, and calibration using programmatic data from Malawi in 2017 where the proportion of people testing HIV positive in facilities was 4%., Results: In the 10% HIV prevalence setting with a triage test, the expected number of FP misclassifications was 0.86 per 10,000 tested without verification testing and the PPV was 99.9%. In the 1% prevalence setting, expected FP misclassifications were 0.19 with 99.8% PPV, and in the Malawi 2017 calibrated setting the expected misclassifications were 0.08 with 99.98% PPV. The cost per FP identified by verification testing was $5879, $3770, and $24,259 respectively. Results were sensitive to assumptions about accuracy of self-reported reactive results and whether reactive triage test results influenced biased interpretation of subsequent RDT results by the HTS provider., Conclusions: Diagnosis with the full algorithm following presentation with a reactive triage test is expected to achieve PPV above the 99% threshold. Continuing verification testing prior to ART initiation remains recommended, but HIV testing strategies involving HIVST and T4T may provide opportunities to maintain quality while increasing efficiency as part of broader restructuring of HIV testing service delivery., (© 2019 World Health Organization; licensed by IAS.)

Introduction: The prevalence of undiagnosed HIV is declining in Africa, and various HIV testing approaches are finding lower positivity rates. In this context, the epidemiological impact and cost-effectiveness of community-based HIV self-testing (CB-HIVST) is unclear. We aimed to assess this in different sub-populations and across scenarios characterized by different adult HIV prevalence and antiretroviral treatment programmes in sub-Saharan Africa., Methods: The synthesis model was used to address this aim. Three sub-populations were considered for CB-HIVST: (i) women having transactional sex (WTS); (ii) young people (15 to 24 years); and (iii) adult men (25 to 49 years). We assumed uptake of CB-HIVST similar to that reported in epidemiological studies (base case), or assumed people use CB-HIVST only if exposed to risk (condomless sex) since last HIV test. We also considered a five-year time-limited CB-HIVST programme. Cost-effectiveness was defined by an incremental cost-effectiveness ratio (ICER; cost-per-disability-adjusted life-year (DALY) averted) below US$500 over a time horizon of 50 years. The efficiency of targeted CB-HIVST was evaluated using the number of additional tests per infection or death averted., Results: In the base case, targeting adult men with CB-HIVST offered the greatest impact, averting 1500 HIV infections and 520 deaths per year in the context of a simulated country with nine million adults, and impact could be enhanced by linkage to voluntary medical male circumcision (VMMC). However, the approach was only cost-effective if the programme was limited to five years or the undiagnosed prevalence was above 3%. CB-HIVST to WTS was the most cost-effective. The main drivers of cost-effectiveness were the cost of CB-HIVST and the prevalence of undiagnosed HIV. All other CB-HIVST scenarios had an ICER above US$500 per DALY averted., Conclusions: CB-HIVST showed an important epidemiological impact. To maximize population health within a fixed budget, CB-HIVST needs to be targeted on the basis of the prevalence of undiagnosed HIV, sub-population and the overall costs of delivering this testing modality. Linkage to VMMC enhances its cost-effectiveness., (© 2019 World Health Organization; licensed by IAS.)

Background: The integrase inhibitor dolutegravir could have a major role in future antiretroviral therapy (ART) regimens in sub-Saharan Africa because of its high potency and barrier to resistance, good tolerability, and low cost, but there is uncertainty over appropriate policies for use relating to the potential for drug resistance spread and a possible increased risk of neural tube defects in infants if used in women at the time of conception. We used an existing individual-based model of HIV transmission, progression, and the effect of ART with the aim of informing policy makers on approaches to the use of dolutegravir that are likely to lead to the highest population health gains., Methods: We used an existing individual-based model of HIV transmission and progression in adults, which takes into account the effects of drug resistance and differential drug potency in determining viral suppression and clinical outcomes to compare predicted outcomes of alternative ART regimen policies. We calculated disability adjusted life-years (DALYs) for each policy, assuming that a woman having a child with a neural tube defect incurs an extra DALY per year for the remainder of the time horizon and accounting for mother-to-child transmission. We used a 20 year time horizon, a 3% discount rate, and a cost-effectiveness threshold of US$500 per DALY averted., Findings: The greatest number of DALYs is predicted to be averted with use of a policy in which tenofovir, lamivudine, and dolutegravir is used in all people on ART, including switching to tenofovir, lamivudine, and dolutegravir in those currently on ART, regardless of current viral load suppression and intention to have (more) children. This result was consistent in several sensitivity analyses. We predict that this policy would be cost-saving., Interpretation: Using a standard DALY framework to compare health outcomes from a public health perspective, the benefits of transition to tenofovir, lamivudine, and dolutegravir for all substantially outweighed the risks., Funding: Bill & Melinda Gates Foundation., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objectives: The objective of this study was to compare the prevalence of polydrug use, use of drugs associated with chemsex, specific drug use, and HIV-related behaviours, between two time periods, using two groups of HIV-negative men who have sex with men (MSM) attending the same sexual health clinics in London and Brighton, in two consecutive periods of time from 2013 to 2016., Methods: Data from MSM in the cross-sectional Attitudes to and Understanding Risk of Acquisition of HIV (AURAH) study (June 2013 to September 2014) were compared with baseline data from different MSM in the prospective cohort study Attitudes to and Understanding Risk of Acquisition of HIV over Time (AURAH2) (November 2014 to April 2016). Prevalence of polydrug use, drug use associated with chemsex and specific drug use, and 10 measures of HIV-related behaviours including condomless sex, post-exposure prophylaxis (PEP) use, pre-exposure prophylaxis (PrEP) use, and HIV testing, were compared. Prevalence ratios (PRs) for the association of the study (time period) with drug use and HIV-related behaviour measures were estimated using modified Poisson regression analysis, unadjusted and adjusted for sociodemographic factors., Results: In total, 991 MSM were included from AURAH and 1031 MSM from AURAH2. After adjustment for sociodemographic factors, use of drugs associated with chemsex had increased (adjusted PR (aPR) 1.30, 95% CI 1.11 to 1.53) and there were prominent increases in specific drug use; in particular, mephedrone (aPR 1.32, 95% CI 1.10 to 1.57), γ-hydroxybutyric/γ-butryolactone (aPR 1.47, 95% CI 1.15 to 1.87) and methamphetamine (aPR 1.42, 95% CI 1.01 to 2.01). Use of ketamine had decreased (aPR 0.54, 95% CI 0.38 to 0.78). Certain measures of HIV-related behaviours had also increased, most notably PEP use (aPR 1.50, 95% CI 1.21 to 1.88) and number of self-reported bacterial STI diagnoses (aPR 1.24, 95% CI 1.08 to 1.43)., Conclusions: There have been significant increases in drug use associated with chemsex and some measures of HIV-related behaviours among HIV-negative MSM in the last few years. Changing patterns of drug use and associated behaviours should be monitored to enable sexual health services to plan for the increasingly complex needs of some clients., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Introduction: The 90-90-90 targets set by the United Nations aspire to 73% of people living with HIV (PLHIV) being virally suppressed by 2020. Using the HIV Synthesis Model, we aim to mimic the epidemic in Zimbabwe and make projections to assess whether Zimbabwe is on track to meet the 90-90-90 targets and assess whether recently proposed UNAIDS HIV transition metrics are likely to be met., Methods: We used an approximate Bayesian computation approach to identify model parameter values which result in model outputs consistent with observed data, evaluated using a calibration score. These parameter values were then used to make projections to 2020 to compare with the 90-90-90 targets and other key indicators. We also calculated HIV transition metrics proposed by UNAIDS (percentage reduction in new HIV infections and AIDS-related mortality from 2010 to 2020, absolute rate of new infections and AIDS-related mortality, incidence-mortality ratio and incidence-prevalence ratios)., Results: After calibration, there was general agreement between modelled and observed data. The median predicted outcomes in 2020 were: proportion of PLHIV (aged 15 to 65) diagnosed 0.91 (90% uncertainty range 0.87, 0.94) (0.84 men, 0.95 women); of those diagnosed, proportion on treatment 0.92 (0.90, 0.93); of those receiving treatment, proportion with viral suppression 0.86 (0.81, 0.91). This results in 72% of PLHIV having viral suppression in 2020. We estimated a percentage reduction of 36.5% (13.7% increase to 67.4% reduction) in new infections from 2010 to 2020, and of 30.4% (9.7% increase to 56.6% reduction) in AIDS-related mortality (UNAIDS target 75%). The modelled absolute rates of HIV incidence and AIDS-related mortality in 2020 were 5.48 (2.26, 9.24) and 1.93 (1.31, 2.71) per 1000 person-years respectively. The modelled incidence-mortality ratio and incidence-prevalence ratios in 2020 were 1.05 (0.46, 1.66) and 0.009 (0.004, 0.013) respectively., Conclusions: Our model was able to produce outputs that are simultaneously consistent with an array of observed data and predicted that while the 90-90-90 targets are within reach in Zimbabwe, increased efforts are required in diagnosing men in particular. Calculation of the HIV transition metrics suggest increased efforts are needed to bring the HIV epidemic under control., (© 2018 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Background: Strengthening engagement of female sex workers with health services is needed to eliminate HIV. We assessed the efficacy of a targeted combination intervention for female sex workers in Zimbabwe., Methods: We did a cluster-randomised trial from 2014 to 2016. Clusters were areas surrounding female sex worker clinics and were enrolled in matched pairs. Sites were randomly assigned (1:1) to receive usual care (free sexual-health services supported by peer educators, including HIV testing on demand, referral for antiretroviral therapy [ART], and health education) or an intervention that supported additional regular HIV testing, on-site initiation of ART, pre-exposure prophylaxis, adherence, and intensified community mobilisation. The primary outcome was the proportion of all female sex workers with HIV viral load 1000 copies per mL or greater, assessed through respondent-driven sampling surveys. We used an adapted cluster-summary approach to estimate risk differences. This trial is registered with Pan African Clinical Trials Registry, number PACTR201312000722390., Results: We randomly assigned 14 clusters to usual care or the intervention (seven in each group). 3612 female sex workers attended clinics in the usual-care clusters and 4619 in the intervention clusters during the study. Half as many were tested (1151 vs 2606) and diagnosed as being HIV positive (546 vs 1052) in the usual-care clusters. The proportion of all female sex workers with viral loads of 1000 copies per mL or greater fell in both study groups (from 421 [30%] of 1363 to 279 [19%] of 1443 in the usual-care group and from 399 [30%] of 1303 to 240 [16%] of 1439 in the intervention group), but with a risk difference at the end of the assessment period of only -2·8% (95% CI -8·1 to 2·5, p=0·23). Among HIV-positive women, the proportions with viral loads less than 1000 copies per mL were 590 (68%) of 869 in the usual-care group and 588 (72%) of 828 in the intervention group at the end of the assessment period, adjusted risk difference of 5·3% (95% CI -4·0 to 14·6, p=0·20). There were no adverse events., Interpretation: Our intervention of a dedicated programme for female sex workers led to high levels of HIV diagnosis and treatment. Further research is needed to optimise programme content and intensity for the broader population., Funding: UN Population Fund (through Zimbabwe's Integrated Support Fund funded by UK Department for International Development, Irish Aid, and Swedish International Development Cooperation Agency)., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: There is concern over increasing prevalence of non-nucleoside reverse-transcriptase inhibitor (NNRTI) resistance in people initiating antiretroviral therapy (ART) in low-income and middle-income countries. We assessed the effectiveness and cost-effectiveness of alternative public health responses in countries in sub-Saharan Africa where the prevalence of pretreatment drug resistance to NNRTIs is high., Methods: The HIV Synthesis Model is an individual-based simulation model of sexual HIV transmission, progression, and the effect of ART in adults, which is based on extensive published data sources and considers specific drugs and resistance mutations. We used this model to generate multiple setting scenarios mimicking those in sub-Saharan Africa and considered the prevalence of pretreatment NNRTI drug resistance in 2017. We then compared effectiveness and cost-effectiveness of alternative policy options. We took a 20 year time horizon, used a cost effectiveness threshold of US$500 per DALY averted, and discounted DALYs and costs at 3% per year., Findings: A transition to use of a dolutegravir as a first-line regimen in all new ART initiators is the option predicted to produce the most health benefits, resulting in a reduction of about 1 death per year per 100 people on ART over the next 20 years in a situation in which more than 10% of ART initiators have NNRTI resistance. The negative effect on population health of postponing the transition to dolutegravir increases substantially with higher prevalence of HIV drug resistance to NNRTI in ART initiators. Because of the reduced risk of resistance acquisition with dolutegravir-based regimens and reduced use of expensive second-line boosted protease inhibitor regimens, this policy option is also predicted to lead to a reduction of overall programme cost., Interpretation: A future transition from first-line regimens containing efavirenz to regimens containing dolutegravir formulations in adult ART initiators is predicted to be effective and cost-effective in low-income settings in sub-Saharan Africa at any prevalence of pre-ART NNRTI resistance. The urgency of the transition will depend largely on the country-specific prevalence of NNRTI resistance., Funding: Bill & Melinda Gates Foundation, World Health Organization., (Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY IGO 3.0 licence. Published by Elsevier Ltd.. All rights reserved.)