Partners PrEP sub-study finds no evidence that PrEP use is associated with risk compensation behaviour

How useful is pre-exposure prophylaxis (PrEP)?  The Partners PrEP randomized control study of daily pre-exposure prophylaxis among HIV-uninfected partners of heterosexual HIV-discordant couples in Uganda and Kenya has indicated that, given adequate adherence, PrEP has high biologic efficacy.  The study itself (Baeten & Celum) demonstrates levels of risk reduction of 75%; while a spin-off sub-study from the original trial, monitoring adherence (STI blog/Haberer & Bangsberg ), has established that, with high adherence (c. 97%), levels of protection are even higher than the study might suggest (none of the 14/1,147 sub-study participants who sero-converted were from the intervention arm of the study).

These results have fed into recent attempts to model the likely effectiveness of PrEP.  The consensus hitherto seems to be that PrEP is a relatively high-cost intervention most likely to be cost-effective as an addition to ART in countries where the burden of HIV is high, and rates of male circumcision low – such as southern Africa (Verguet & WalshYing and Barnabas).

Last month saw the online publication of a second interesting spin-off sub-study of Partners PrEP (Mugwanya & Baeten).  It undertakes a longitudinal analysis of data from the original trial to address what is perhaps the greatest concern affecting the implementation of PrEP as a public health intervention (STI blog/Sugarman & Mayer), that of risk compensation – i.e. the possibility that the security promised by PrEP will itself encourage sexual risk-taking behaviour.  M&B’s results, along with those of any future studies of this issue, will no doubt serve to inform the assumptions of future models.

In July 2011 the Partners PrEP study reported its findings, and the placebo arm of the trial was closed.  However, follow-up of 3,024 participants continued.  This allowed data on their sexual activity to be collected over a period which spanned the 12 months preceding – and the 12 months following – the disclosure to participants of the results of the study.  These data included unprotected sex acts and total sex acts over this period, both within the primary relationship as registered by the study and outside that relationship.

Within the primary relationship (i.e. with the registered HIV-infected partner), the crude average frequency of unprotected/total sex acts within the primary relationship was 59/414 per 100 person- months prior to, and 53/361 following, unmasking.  Outside that primary relationship the frequency of unprotected total sex acts was 49/62 as opposed to 67/84. So there appears to be a fall in unprotected/total sex acts with the primary sex partner as between the two halves of the period, and a small, but significant, rise in unprotected/total sex acts outside this relationship.  The latter rise (unprotected sex acts outside the primary relationship) is helpfully quantified at an average of 6.8 sex acts per year following unmasking as against an average of 6.2 acts in a predicted counterfactual scenario had patients remained unmasked.  M&B place this figure in the context of the estimated doubling of risk-behaviour, which modellers suggest would be required in order to see any attenuation in the effectiveness of PrEP.

The authors suggest – optimistically perhaps – that the small decrease in unprotected sex following enrolment indicates that PrEP delivered in the context of an HIV prevention package may be synergistic for risk reduction.  However, they also point to an earlier study (Ndase & Thomas) that finds this overall pattern of decline in sex acts with primary partner and rise in sex acts outside the primary relationship to be indicative of dissolution of the primary relationship and formation of new relationships.  They also observe that unprotected sex without outside partners was “high among the few participants who reported sex outside the primary partnership” – an observation that accords with recent study findings that a quarter of HIV infections in sero-discordant partnerships arise from non-primary partners.

The findings of the study seem reassuring.  They raise two questions, however.  The first concerns the impact of the probable gap between the HIV prevention package accompanying any real-life PrEP implementation and the package made available to the participants in Partners-PrEP.  The second concerns the impact of new partnership formation on unprotected sex over the longer term.  It is here that the findings of M&B would lead us to expect the greatest challenge to PrEP; yet the true extent of such a challenge is something of which their study can offer us only the most preliminary impression.

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