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

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          Abstract

          Introduction

          HIV pre‐exposure prophylaxis (PrEP) has been recommended and partly subsidized in Québec, Canada, since 2013. We evaluated the population‐level impact of PrEP on HIV transmission among men who have sex with men (MSM) in Montréal, Québec's largest city, over 2013–2021.

          Methods

          We used an agent‐based mathematical model of sexual HIV transmission to estimate the fraction of HIV acquisitions averted by PrEP compared to a counterfactual scenario without PrEP. The model was calibrated to local MSM survey, surveillance, and cohort data and accounted for COVID‐19 pandemic impacts on sexual activity, HIV prevention, and care. PrEP was modelled from 2013 onwards, assuming 86% individual‐level effectiveness. The PrEP eligibility criteria were: any anal sex unprotected by condoms (past 6 months) and either multiple partnerships (past 6 months) or multiple uses of post‐exposure prophylaxis (lifetime). To assess potential optimization strategies, we modelled hypothetical scenarios prioritizing PrEP to MSM with high sexual activity (≥11 anal sex partners annually) or aged ⩽45 years, increasing coverage to levels achieved in Vancouver, Canada (where PrEP is free‐of‐charge), and improving retention.

          Results

          Over 2013–2021, the estimated annual HIV incidence decreased from 0.4 (90% credible interval [CrI]: 0.3–0.6) to 0.2 (90% CrI: 0.1–0.2) per 100 person‐years. PrEP coverage among HIV‐negative MSM remained low until 2015 (<1%). Afterwards, coverage increased to a maximum of 10% of all HIV‐negative MSM, or about 16% of the 62% PrEP‐eligible HIV‐negative MSM in 2020. Over 2015–2021, PrEP averted an estimated 20% (90% CrI: 11%–30%) of cumulative HIV acquisitions. The hypothetical scenarios modelled showed that, at the same coverage level, prioritizing PrEP to high sexual activity MSM could have averted 30% (90% CrI: 19%–42%) of HIV acquisitions from 2015‐2021. Even larger impacts could have resulted from higher coverage. Under the provincial eligibility criteria, reaching 10% coverage among HIV‐negative MSM in 2015 and 30% in 2019, like attained in Vancouver, could have averted up to 63% (90% CrI: 54%–70%) of HIV acquisitions from 2015 to 2021.

          Conclusions

          PrEP reduced population‐level HIV transmission among Montréal MSM. However, our study suggests missed prevention opportunities and adds support for public policies that reduce PrEP barriers, financial or otherwise, to MSM at risk of HIV acquisition.

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          Most cited references47

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          Preexposure Chemoprophylaxis for HIV Prevention in Men Who Have Sex with Men

          Antiretroviral chemoprophylaxis before exposure is a promising approach for the prevention of human immunodeficiency virus (HIV) acquisition. We randomly assigned 2499 HIV-seronegative men or transgender women who have sex with men to receive a combination of two oral antiretroviral drugs, emtricitabine and tenofovir disoproxil fumarate (FTC-TDF), or placebo once daily. All subjects received HIV testing, risk-reduction counseling, condoms, and management of sexually transmitted infections. The study subjects were followed for 3324 person-years (median, 1.2 years; maximum, 2.8 years). Of these subjects, 10 were found to have been infected with HIV at enrollment, and 100 became infected during follow-up (36 in the FTC-TDF group and 64 in the placebo group), indicating a 44% reduction in the incidence of HIV (95% confidence interval, 15 to 63; P=0.005). In the FTC-TDF group, the study drug was detected in 22 of 43 of seronegative subjects (51%) and in 3 of 34 HIV-infected subjects (9%) (P<0.001). Nausea was reported more frequently during the first 4 weeks in the FTC-TDF group than in the placebo group (P<0.001). The two groups had similar rates of serious adverse events (P=0.57). Oral FTC-TDF provided protection against the acquisition of HIV infection among the subjects. Detectable blood levels strongly correlated with the prophylactic effect. (Funded by the National Institutes of Health and the Bill and Melinda Gates Foundation; ClinicalTrials.gov number, NCT00458393.).
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            Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label randomised trial

            Summary Background Randomised placebo-controlled trials have shown that daily oral pre-exposure prophylaxis (PrEP) with tenofovir–emtricitabine reduces the risk of HIV infection. However, this benefit could be counteracted by risk compensation in users of PrEP. We did the PROUD study to assess this effect. Methods PROUD is an open-label randomised trial done at 13 sexual health clinics in England. We enrolled HIV-negative gay and other men who have sex with men who had had anal intercourse without a condom in the previous 90 days. Participants were randomly assigned (1:1) to receive daily combined tenofovir disoproxil fumarate (245 mg) and emtricitabine (200 mg) either immediately or after a deferral period of 1 year. Randomisation was done via web-based access to a central computer-generated list with variable block sizes (stratified by clinical site). Follow-up was quarterly. The primary outcomes for the pilot phase were time to accrue 500 participants and retention; secondary outcomes included incident HIV infection during the deferral period, safety, adherence, and risk compensation. The trial is registered with ISRCTN (number ISRCTN94465371) and ClinicalTrials.gov (NCT02065986). Findings We enrolled 544 participants (275 in the immediate group, 269 in the deferred group) between Nov 29, 2012, and April 30, 2014. Based on early evidence of effectiveness, the trial steering committee recommended on Oct 13, 2014, that all deferred participants be offered PrEP. Follow-up for HIV incidence was complete for 243 (94%) of 259 patient-years in the immediate group versus 222 (90%) of 245 patient-years in the deferred group. Three HIV infections occurred in the immediate group (1·2/100 person-years) versus 20 in the deferred group (9·0/100 person-years) despite 174 prescriptions of post-exposure prophylaxis in the deferred group (relative reduction 86%, 90% CI 64–96, p=0·0001; absolute difference 7·8/100 person-years, 90% CI 4·3–11·3). 13 men (90% CI 9–23) in a similar population would need access to 1 year of PrEP to avert one HIV infection. We recorded no serious adverse drug reactions; 28 adverse events, most commonly nausea, headache, and arthralgia, resulted in interruption of PrEp. We detected no difference in the occurrence of sexually transmitted infections, including rectal gonorrhoea and chlamydia, between groups, despite a suggestion of risk compensation among some PrEP recipients. Interpretation In this high incidence population, daily tenofovir–emtricitabine conferred even higher protection against HIV than in placebo-controlled trials, refuting concerns that effectiveness would be less in a real-world setting. There was no evidence of an increase in other sexually transmitted infections. Our findings strongly support the addition of PrEP to the standard of prevention for men who have sex with men at risk of HIV infection. Funding MRC Clinical Trials Unit at UCL, Public Health England, and Gilead Sciences.
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              On-Demand Preexposure Prophylaxis in Men at High Risk for HIV-1 Infection.

              Antiretroviral preexposure prophylaxis has been shown to reduce the risk of human immunodeficiency virus type 1 (HIV-1) infection in some studies, but conflicting results have been reported among studies, probably due to challenges of adherence to a daily regimen.
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                Author and article information

                Contributors
                mathieu.maheu-giroux@mcgill.ca
                Journal
                J Int AIDS Soc
                J Int AIDS Soc
                10.1002/(ISSN)1758-2652
                JIA2
                Journal of the International AIDS Society
                John Wiley and Sons Inc. (Hoboken )
                1758-2652
                06 December 2023
                December 2023
                : 26
                : 12 ( doiID: 10.1002/jia2.v26.12 )
                : e26194
                Affiliations
                [ 1 ] Department of Epidemiology and Biostatistics School of Population and Global Health McGill University Montréal Québec Canada
                [ 2 ] Direction Régionale de Santé Publique de Montréal Montréal Québec Canada
                [ 3 ] Clinical Outcomes Research and Evaluation Research Institute ‐ McGill University Health Centre Montréal Québec Canada
                [ 4 ] Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM) Montréal Québec Canada
                [ 5 ] Département de Microbiologie Infectiologie et Immunologie Université de Montréal Montréal Québec Canada
                [ 6 ] Département de Sexologie Université du Québec à Montréal Montréal Québec Canada
                [ 7 ] MRC Centre for Global Infectious Disease Analysis School of Public Health Imperial College London London UK
                [ 8 ] Department of Family Medicine Centre Hospitalier de l'Université de Montréal Montréal Québec Canada
                [ 9 ] Clinique de médecine urbaine du Quartier Latin Montréal Québec Canada
                [ 10 ] Clinique médicale l'Actuel Montréal Québec Canada
                [ 11 ] RÉZO Health and STI prevention for GBQ men, trans people and MSM Montréal Québec Canada
                [ 12 ] Dalla Lana School of Public Health University of Toronto Toronto Ontario Canada
                [ 13 ] BC Centre for Excellence in HIV/AIDS Vancouver British Columbia Canada
                [ 14 ] Faculty of Medicine University of British Columbia Vancouver British Columbia Canada
                [ 15 ] Department of Medicine St. Michael's Hospital University of Toronto Toronto Ontario Canada
                [ 16 ] Institute of Medical Sciences University of Toronto Toronto Ontario Canada
                [ 17 ] Institute of Health Policy Management and Evaluation Dalla Lana School of Public Health University of Toronto Toronto Ontario Canada
                Author notes
                [*] [* ] Corresponding author: Mathieu Maheu‐Giroux, 2001 McGill College, Suite 1200, Montréal, QC H3A 1G1, Canada. Tel: 1 (514) 398–5110. ( mathieu.maheu-giroux@ 123456mcgill.ca )

                Author information
                https://orcid.org/0000-0001-5104-3068
                https://orcid.org/0000-0003-1078-9247
                https://orcid.org/0000-0001-8492-5470
                https://orcid.org/0000-0002-8363-4388
                Article
                JIA226194
                10.1002/jia2.26194
                10699110
                38054579
                e59af44f-26bc-4aa9-8163-806081881a79
                © 2023 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 28 June 2023
                : 17 November 2023
                Page count
                Figures: 5, Tables: 3, Pages: 13, Words: 8971
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                December 2023
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.3.5 mode:remove_FC converted:06.12.2023

                Infectious disease & Microbiology
                antiretroviral,combination prevention,elimination,epidemiology,impact evaluation,mathematical modelling,sexually transmitted and blood‐borne infections

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