{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T20:10:26Z","timestamp":1793823026012,"version":"4.6.1"},"reference-count":35,"publisher":"BMJ","issue":"5","license":[{"start":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T00:00:00Z","timestamp":1652140800000},"content-version":"unspecified","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2022,2,7]]},"published-print":{"date-parts":[[2022,5]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To conduct a systematic review and meta-analysis of randomised controlled trials (RCTs) of the effectiveness and safety of oral pre-exposure prophylaxis (PrEP) to prevent HIV.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Databases (PubMed, Embase and the Cochrane Register of Controlled Trials) were searched up to 5 July 2020. Search terms for \u2018HIV\u2019 were combined with terms for \u2018PrEP\u2019 or \u2018tenofovir\/emtricitabine\u2019. RCTs were included that compared oral tenofovir-containing PrEP to placebo, no treatment or alternative medication\/dosing schedule. The primary outcome was the rate ratio (RR) of HIV infection using a modified intention-to-treat analysis. Secondary outcomes included safety, adherence and risk compensation. All analyses were stratified a priori by population: men who have sex with men (MSM), serodiscordant couples, heterosexuals and people who inject drugs (PWIDs). The quality of individual studies was assessed using the Cochrane risk-of-bias tool, and the certainty of evidence was assessed using GRADE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Of 2803 unique records, 15 RCTs met our inclusion criteria. Over 25 000 participants were included, encompassing 38 289 person-years of follow-up data. PrEP was found to be effective in MSM (RR 0.25, 95% CI 0.1 to 0.61; absolute rate difference (RD) \u22120.03, 95% CI \u22120.01 to \u22120.05), serodiscordant couples (RR 0.25, 95% CI 0.14 to 0.46; RD \u22120.01, 95% CI \u22120.01 to \u22120.02) and PWID (RR 0.51, 95% CI 0.29 to 0.92; RD \u22120.00, 95% CI \u22120.00 to \u22120.01), but not in heterosexuals (RR 0.77, 95% CI 0.46 to 1.29). Efficacy was strongly associated with adherence (p&lt;0.01). PrEP was found to be safe, but unrecognised HIV at enrolment increased the risk of viral drug resistance mutations. Evidence for behaviour change or an increase in sexually transmitted infections was not found.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>PrEP is safe and effective in MSM, serodiscordant couples and PWIDs. Additional research is needed prior to recommending PrEP in heterosexuals. No RCTs reported effectiveness or safety data for other high-risk groups, such as transgender women and sex workers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PROSPERO registration number<\/jats:title>\n                    <jats:p>CRD42017065937.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2020-048478","type":"journal-article","created":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T06:47:31Z","timestamp":1652770051000},"page":"e048478","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":262,"title":["Oral pre-exposure prophylaxis (PrEP) to prevent HIV: a systematic review and meta-analysis of clinical effectiveness, safety, adherence and risk compensation in all populations"],"prefix":"10.1136","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3926-0179","authenticated-orcid":false,"given":"Eamon","family":"O Murchu","sequence":"first","affiliation":[{"name":"Health Technology Assessment Directorate, Health Information and Quality Authority, Dublin 7, Ireland"},{"name":"Centre for Health Policy and Management, Trinity College Dublin, Dublin 2, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liam","family":"Marshall","sequence":"additional","affiliation":[{"name":"Health Technology Assessment Directorate, Health Information and Quality Authority, Dublin 7, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Conor","family":"Teljeur","sequence":"additional","affiliation":[{"name":"Health Technology Assessment Directorate, Health Information and Quality Authority, Dublin 7, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Harrington","sequence":"additional","affiliation":[{"name":"Health Technology Assessment Directorate, Health Information and Quality Authority, Dublin 7, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1576-4623","authenticated-orcid":false,"given":"Catherine","family":"Hayes","sequence":"additional","affiliation":[{"name":"TCD Institute of Population Health, Tallaght, Trinity College Dublin, Dublin 24, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Moran","sequence":"additional","affiliation":[{"name":"Health Technology Assessment Directorate, Health Information and Quality Authority, Dublin 7, Ireland"},{"name":"Centre for Health Policy and Management, Trinity College Dublin, Dublin 2, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mairin","family":"Ryan","sequence":"additional","affiliation":[{"name":"Health Technology Assessment Directorate, Health Information and Quality Authority, Dublin 7, Ireland"},{"name":"Department of Pharmacology and Therapeutics, Trinity Health Sciences, Trinity College Dublin, Dublin 8, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2022,5,11]]},"reference":[{"key":"2025121605143231000_12.5.e048478.1","unstructured":"UNAIDS . Global HIV & AIDS statistics \u2014 2020 fact sheet, 2020. Available: https:\/\/www.unaids.org\/en\/resources\/fact-sheet [Accessed 11 Sep 2021]."},{"key":"2025121605143231000_12.5.e048478.2","unstructured":"WHO . Consolidated guidelines on HIV prevention, diagnosis, treatment and care for key populations, 2014. Available: https:\/\/www.who.int\/hiv\/pub\/guidelines\/keypopulations\/en\/ [Accessed 22 Jul 2019]."},{"key":"2025121605143231000_12.5.e048478.3","doi-asserted-by":"crossref","first-page":"2587","DOI":"10.1056\/NEJMoa1011205","article-title":"Preexposure chemoprophylaxis for HIV prevention in men who have sex with men","volume":"363","author":"Grant","year":"2010","journal-title":"N Engl J Med Overseas Ed"},{"key":"2025121605143231000_12.5.e048478.4","unstructured":"WHO . WHO expands recommendation on oral preexposure prophylaxis of HIV infection (PreP), 2015. Available: https:\/\/apps.who.int\/iris\/bitstream\/handle\/10665\/197906\/WHO_HIV_2015.48_eng.pdf;jsessionid=7B04813AFDE92D7F5EE3D71C8E921BBA?sequence=1 [Accessed 22 Jul 2019]."},{"key":"2025121605143231000_12.5.e048478.5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1506273"},{"key":"2025121605143231000_12.5.e048478.6","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)00056-2"},{"key":"2025121605143231000_12.5.e048478.7","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1202614"},{"key":"2025121605143231000_12.5.e048478.8","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.b2700"},{"key":"2025121605143231000_12.5.e048478.9","unstructured":"GRADE . The grading of recommendations assessment, development and evaluation (short grade) Working group. Available: http:\/\/www.gradeworkinggroup.org\/"},{"key":"2025121605143231000_12.5.e048478.10","unstructured":"Cochrane . The Cochrane risk of bias tool. Cochrane Handbook: chapter 8. 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Clinical management guidance for individuals taking HIV PrEP within the context of a combination HIV (and STI) prevention approach in Ireland. PrEP clinical management guidance. version 1.1. October 2019, 2019. Available: https:\/\/www.sexualwellbeing.ie\/for-professionals\/prep-information-for-service-providers\/guidelines-for-the-management-of-prep-in-ireland.pdf [Accessed 11 Sep 2021]."},{"key":"2025121605143231000_12.5.e048478.31","unstructured":"Department of Health . Taoiseach and ministers for health announce HIV PreP programme: press release. published on 10 October 2019, 2019. Available: https:\/\/www.gov.ie\/en\/press-release\/taoiseach-and-ministers-for-health-announce-hiv-prep-programme\/ [Accessed 11 Sep 2021]."},{"key":"2025121605143231000_12.5.e048478.32","unstructured":"Health Protection Surveillance Centre (HPSC) . HIV in Ireland, 2018. Annual epidemiological report, 2019. Available: https:\/\/www.hpsc.ie\/a-z\/hivandaids\/hivdataandreports\/HIV_2018_finalrev.pdf [Accessed 11 Sep 2021]."},{"key":"2025121605143231000_12.5.e048478.33","doi-asserted-by":"crossref","DOI":"10.3389\/fphar.2018.00799","article-title":"Efficacy and safety of oral TDF-Based pre-exposure prophylaxis for men who have sex with men: a systematic review and meta-analysis","volume":"9","author":"Huang","year":"2018","journal-title":"Front Pharmacol"},{"key":"2025121605143231000_12.5.e048478.34","doi-asserted-by":"publisher","DOI":"10.1111\/jocn.13990"},{"key":"2025121605143231000_12.5.e048478.35","doi-asserted-by":"crossref","unstructured":"Okwundu CI , Uthman OA , Okoromah CAN . Antiretroviral preexposure prophylaxis (PreP) for preventing HIV in highrisk individuals. 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