The year 2015 is likely to turn out a decisive one for the story of PrEP (pre-exposure prophylaxis for HIV). After a slow and faltering beginning, with trials in sub-Saharan Africa dogged by problems of poor adherence (Haberer & Bangsburg/STI/blog; VOICE D/STI/blog; Hendrix & Bumpus/STI/blog), this intervention appears at last to have proved its worth – at least in high-risk populations such as MSM in Europe and America. This is to be seen in a succession of results from recent or still ongoing trials.
Following the report of encouraging headline figures at last February’s Conference on Retroviruses and Opportunistic Infections (CROI), the UK PROUD study (Pre-exposure Option for reducing HIV in the UK immediate or Deferred) has published its results (McCormack & Gill; PROUD/STI/blog). As stated in my earlier blog, this study, based in 13 UK clinics, aimed, in its design, to replicate real-life conditions in being an ‘open-label’, as opposed to a blind placebo controlled, randomized study. September also saw the publication of a brief report of a San Francisco based study (Volk & Hare) investigating HIV and STI incidence amongst a comparable number of patients (650) referred for PrEP over 2 and a half year period in a clinical practice under the health insurance provider Kaiser Permanente. Finally, the PROUD study refers to the still ongoing IPERGAY study run by French and Canadian researchers (IPERGAY; Molina & Delfraissy). The latter differs from the PROUD study, first in respect to the PrEP regime followed, which is ‘on demand’ (i.e. before and after sex) rather than daily; second, in having a blind placebo controlled, rather than an ‘open-label’, design.
The three studies investigate relatively high-risk, largely MSM, populations – to judge by the high rates (c. 34%-50% within a year of follow-up) of STIs and especially (18%-32%) of rectal STIs. Rates of HIV transmission, however, were, in all cases, similarly low. As indicated in my blog (PROUD/STI/blog), the PROUD study headlined an HIV incidence of 1-2 per 100 person years (py) in the immediate initiation, as against 9 per 100 py in the ‘deferred initiation’ arm. The IPERGAY study saw rates of 0.94 as against 6.75. The San Francisco study was without a control arm, but saw zero cases of HIV among PrEP users over the two and a half year study period. All this would suggest that amongst self-selecting high-risk MSM, PrEP interventions can be successful in preventing HIV transmission. It would, however, be reassuring to know more about the impact of PrEP on risk compensation – always the supposed ‘Achilles heel’ of MSM PrEP (Cassell & Halperin) – especially as rates of STI incidence following PrEP initiation were very high in all studies. Here the published version of the PROUD study has the advantage of being able to compare incidence of other STIs between the intervention and the control arm of the study. No significant difference between the two arms was observed. This was particularly encouraging as the PROUD study was designed to replicate the conditions of a real-life intervention in that those in the intervention arm knew they were taking PrEP, and could have adjusted their behaviour on the basis of this knowledge.
A final issue that PROUD and IPERGAY may begin to help health professionals to address is that of cost effectiveness. The PROUD researchers calculate that ‘thirteen men in a similar population would need access to 1 year of PrEP to avert 1 HIV infection’. This would make PrEP targeted at this group cost-effective at current prices if the cost of tenofovir and emtricitibine were halved. It could also be achieved if the proposed intervention were to adopt the ‘on demand’ regimen trialled by IPERGAY: namely, two tablets 2-24 hrs before sex, one taken 24hr, and a further tablet 48 hrs. after. IPERGAY, it will be remembered, demonstrated the same 86% reduction in HIV incidence that was observed by PROUD.