Long-term follow-up of PROUD: evidence for high continued HIV exposure and durable effectiveness of PrEP

Background: The PROUD trial clearly demonstrated the clinical effectiveness of TDF/FTC in the first year of use. The continued follow-up of participants on PrEP (range 2-4 years), which included regular testing for HIV and other STIS, allows assessment on whether effectiveness is maintained in the longer term and the extent of potential exposure to HIV.
Methods: PROUD was a pragmatic trial in which MSM were randomised to receive daily TDF/FTC either immediately (IMM) or after a deferral (DEF) period of 12 months. Main efficacy findings were based on follow-up during the deferred phase when IMM had access to PrEP and DEF did not. Since Nov 14, when all participants were offered PrEP, the trial has entered a post-deferred phase. We compare incidence rates of HIV and selective STIs during the deferred and post-deferred phases.
Results: 524(269 IMM, 255 DEF) and 449(244 IMM, 205 DEF) participants contributed to the deferred and post-deferred phases. Of 368 who attended a clinic in the last 6 months of follow-up, 327(89%) had at least one PrEP prescription. HIV and rectal gonorrhoea(rGC)/chlamydia(rCT) incidence in each phase is shown by group in the table.

 Deferred PhasePost-deferred Phase
InfectionIMMDEFIMMDEF
HIV1.6 (4/254)9.4 (21/223)1.2 (5/423)0.3 (1/353)
Rectal GC35.3 (81/229)33.1 (67/203)31.4 (129/411)32.7 (116/355)
Rectal CT33.6 (77/229)21.2 (43/203)33.1 (136/411)29.9 (106/355)
[HIV and STI incidence (per 100 PY)]


There was no difference in HIV incidence between the groups in the post-deferred phase (p=0.18), but a significant decrease in the DEF group once they had access to PrEP (p< 0.0001). The rate in the IMM group remained similar in the two phases (p=0.66). The incidence of rectal infections was high in both groups and phases. rCT was lowest in the DEF group during the deferred phase, and this was driven by those who did not report rCT in the year before enrolment.
Conclusions: The reduction in HIV incidence in the DEF group confirms the remarkable effectiveness of TDF/FTC. The relatively stable incidence in the IMM group indicates this effect is durable. High ongoing incidence of rCT/rGC shows that participants remained at high risk of HIV and this needs to be taken into account when planning PrEP provision in public health programmes.

E. White1, D. Dunn1, R. Gilson2, A. Sullivan3, A. Clarke4, I. Reeves5, G. Schembri6, N. Mackie7, C. Dewsnap8, C. Lacey9, V. Apea10, M. Brady11, J. Fox12, S. Taylor13, J. Rooney14, M. Gafos1, O.N. Gill15, S. McCormack1,16, PROUD Study Group
1MRC CTU at UCL, UCL, London, United Kingdom, 2Mortimer Market Centre, Central and North West London NHS Foundation Trust, London, United Kingdom, 3St Stephen's Centre, Chelsea & Westminster NHS Foundation Trust, London, United Kingdom, 4Royal Sussex County Hospital, Brighton & Sussex University Hospitals NHS Trust, Brighton, United Kingdom, 5Homerton University Hospital NHS Foundation Trust, London, United Kingdom, 6Manchester Centre for Sexual Health, Central Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom, 7St Mary's Hospital, Imperial College Healthcare NHS Foundation Trust, London, United Kingdom, 8Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield, United Kingdom, 9York Teaching Hospital and Hull York Medical School, University of York, York, United Kingdom, 10Ambrose King Centre and Barts Sexual Health Centre, Barts Health NHS Trust, London, United Kingdom, 11King's College Hospital NHS Foundation Trust, London, United Kingdom, 12Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom, 13Birmingham Heartlands Hospital, Heart of England NHS Foundation Trust, Birmingham, United Kingdom, 14Gilead Sciences, Foster City, United States, 15HIV & STI Department, Public Health England Centre for Infectious Disease Surveillance and Control, London, United Kingdom, 1656 Dean Street, Chelsea and Westminster Hospital NHS Foundation Trust, London, United Kingdom