Objectives Pre-exposure prophylaxis (PrEP) is a highly effective method of HIV prevention for men who have sex with men (MSM). However, uncertainty remains around the optimal eligibility criteria for PrEP, specifically whether there are subgroups at low risk of HIV for whom PrEP might not be warranted.
Methods PROUD was an open-label waitlist trial design that randomised MSM attending participating sexual health centres in England to receive PrEP immediately (IMM) or after a deferral period of 1 year (DEF). This analysis is based on participants who were randomised to the deferred arm, when they did not have access to PrEP. HIV incidence was compared between subgroups defined by baseline characteristics.
Results Overall, 21 participants acquired HIV infection over 239.3 person-years (PY) follow-up, yielding an incidence rate of 8.8/100 PY (95% CI 5.4 to 13.4). Two highly significant predictors for HIV acquisition were identified. Men with a self-reported diagnosis of syphilis, rectal chlamydia (CT) or rectal gonorrhoea (GC) in the previous 12 months had an incidence of 17.2/100 PY (95% CI 9.7 to 28.5); those reporting receptive anal intercourse without a condom (ncRAI) with two or more partners in the previous 3 months had an incidence of 13.6/100 PY (95% CI 7.9 to 21.7). The incidence rate among participants lacking both of these risk factors was 1.1/100 PY (1/87.6, 95% CI 0.03 to 6.4).
Conclusions The high HIV incidence in PROUD suggests that most participants appropriately judged their need for PrEP. Eligibility criteria for a PrEP programme can therefore be broad, as in the current guidelines. However, a recent history of syphilis or rectal CT/GC, or multiple ncRAI partners indicates a high imminent risk of HIV infection. MSM with any of these characteristics should be offered PrEP as a matter of urgency.
- eligibility criteria
This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.
Statistics from Altmetric.com
Handling editor Henry John Christiaan de Vries
Collaborators PROUD study group: David I Dolling, Monica Desai, Alan McOwan, Richard Gilson, Amanda Clarke, Martin Fisher, Gabriel Schembri, Ann K Sullivan, Nicola Mackie, Iain Reeves, Mags Portman, John Saunders, Julie Fox, Jake Bayley, Michael Brady, Christine Bowman, Charles J Lacey, Stephen Taylor, David White, Simone Antonucci, Mitzy Gafos, Sheena McCormack, Owen N Gill, David T Dunn and Anthony Nardone. PROUD clinic teams: Vanessa Apea, Drew Clark, Paul Davis, James Hand, Machel Hunt, Rebecca Neale, Jackie O’Connell, Margaret Portman, Liat Sarner, John Saunders, Louise Terry, Angelina Twumasi, Salina Tsui, Dayan Vijeratnam, Ryan Whyte, Andy Williams (Barts), Sian Gately, Gerry Gilleran, Jill Lyons, Chris McCormack, Katy Moore, Cathy Stretton, Stephen Taylor, David White (Birmingham), Alex Acheampong, Michael Bramley, Marion Campbell, Ruby Chowdhry, Amanda Clarke, Stewart Eastwood, Babs Fennell, Martin Fisher, Wendy Hadley, Kerry Hobbs, Sarah Kirk, Nicky Perry, Charlotte Rawlinson, Celia Richardson, Claire Richardson, Mark Roche, Emma Simpkin, Simon Shaw, Elisa Souto, Julia Williams, Elaney Youssef (Brighton), Simone Antonucci, Tristan Barber, Cindy Eliot, Serge Fedele, Chris Higgs, Kathryn McCormick, Sheena McCormack, Alan McOwan, Alexandra Meijer, Sam Pepper, Jane Rowlands, Gurmit Singh, Alfredo SolerCarracedo, Sonali Sonecha, Ann Sullivan, David Taylor, Lervina Thomas (Chelsea and Westminster), Frederick Attakora, Marina Bourke, Richard Castles, Rebecca Clark, Anke De-Masi, Veronica Espa, Rumbidzai Hungwe, Martin Lincoln, Sifiso Mguni, Rhianon Nevin-Dolan, Iain Reeves (Homerton), Hannah Alexander, Jake Bayley, Michael Brady, Lucy Campbell, Sophie Candfield, Shema Doshi, Olivia Liddle, Larissa Mulka, Priyanka Saigal, James Stevenson (King’s), James Boateng, Brynn Chappell, Susanna Currie, Carolyn Davies, Dornubari Lebari, Matthew Phillips, Gabriel Schembri, Lisa Southon, Sarah Thorpe, Anna Vas, Chris Ward, Claire Warren, Stephanie Yau (Manchester), Alejandro Arenas-Pinto, Asma Ashraf, Matthew Bolton, Richard Gilson, Lewis Haddow, Sara McNamara, Ana Milinkovic, June Minton, Dianne Morris, Clare Oakland, Steve O’Farrell, Pierre Pellegrino, Sarah Pett, Nina Vora, Carmel Young, Taris Zarko-Flynn (Mortimer Market), Wilbert Ayap, Ling Jun Chen, Adam Croucher, Sarah Fidler, Kristin Kuldanek, Ken Legg, Agathe Leon, Nicola Mackie, Nadia Naous, Killian Quinn, Severine Rey, Judith Zhou (St Marys), Margaret-Anne Bevan, Julie Fox, Nina Francia, Eleanor Hamlyn, Lisa Hurley, Helen Iveson, Isabelle Jendrulek, Tammy Murray, Alice Sharp, Andrew Skingsley, Chi Kai Tam, Al Teague, Caroline Thomas, Juan-Manuel Tiraboschi (St Thomas’), Christine Brewer, Richard Evans, Jan Gravely, Charles Lacey, Gary Lamont, Fabiola Martin, Georgina Morris, Sarah Russell-Sharpe, John Wightman (York), Anthony Bains, Gill Bell, Christine Bowman, Terry Cox, Claire Dewsnap, Charlie Hughes, Hannah Loftus, Naomi Sutton, Debbie Talbot, Vince Tucker (Sheffield). MRC CTU at UCL: Sarah Banbury, Elizabeth Brodnicki, Christina Chung, David I Dolling, David T Dunn, Keith Fairbrother, Michelle Gabriel, Mitzy Gafos, Sajad Khan, Shabana Khan, Sheena McCormack, Brendan Mauger, Gemma Sancha, Annabelle South, Yinka Sowunmi, Susan Spencer and Ellen White. Social Science team: Gill Bell, Caroline Rae, Michael Rayment, Will Nutland and Sonali Wayal. Public Health England: Monica Desai, Sarika Desai, Nigel Field, Noel Gill, Kate Hyland, Peter Kirwan, Anthony Nardone and Parnam Seyan. Gilead Sciences: Rich Clarke and Jim Rooney.
Contributors SM led the study. DTD, MD, MG and SM conceived and designed the study. AKS, AC and SM recruited participants and collected data. EW conducted the analyses and led the writing on this paper. PK conducted the participant matching. All authors read and approved the final manuscript. EW had full access to all the data in the study and had final responsibility for the decision to submit for publication.
Funding The PROUD trial was supported by ad hoc funding from the Medical Research Council (MRC) Clinical Trials Unit at University College London and an innovations grant from Public Health England, and most clinics received support through the UK NIHR Clinical Research Network. Gilead Sciences provided Truvada, distributed drug to clinics and awarded a grant for the additional diagnostic tests including drug concentrations in plasma. EW, DTD and SM were supported by the UK Medical Research Council (MRC_UU_12023/23) during preparation of and outside the submitted work.
Competing interests The PROUD study was provided drug free of charge by Gilead Sciences which also distributed it to participating clinics and provided funds for additional diagnostic tests for HCV and drug levels. EW's university fees and stipend were funded by Gilead Sciences. DTD has received fees for participation on advisory boards and educational workshops from ViiV Healthcare and Gilead Sciences. PK was part funded by Gilead Sciences during 2017/2018. AC received advisory board fees from Gilead Sciences and GSK/ViiV; speaker fees from Gilead and conferences bursaries from Gilead & Janssen. SM reports grants from the European Union H2020 scheme, EDCTP 2, the National Institute of Health Research and Gilead Sciences; other support from Gilead Sciences, and the Population Council Microbicide Advisory Board; and is Chair of the Project Advisory Committee for USAID grant awarded to CONRAD to develop tenofovir-based products for use by women (non-financial).
Patient consent for publication Not required.
Ethics approval The study was reviewed and approved by the London Bridge Research Ethics Committee (REC number: 12/LO/1289). The study protocol is available online (http://www.proud.mrc.ac.uk/about/study-protocol/).
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement The PROUD data are held at MRC CTU at UCL, which encourages optimal use of data by employing a controlled access approach to data sharing, incorporating a transparent and robust system to review requests and provide secure data access consistent with the relevant ethics committee approvals. All requests for data are considered and can be initiated by contacting email@example.com.
If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.