Failed PrEP trial (VOICE) participants give reasons for their poor adherence

Despite indications of the acceptability of Pre-Exposure Prophylaxis (PrEP) among certain populations (MSM in London (STI/Aghaizu & Nardone) 2013, and Australia (STI/Holt & De Wit) 2012), the extremely varied results that have emanated from large studies seeking to determine its efficacy and effectiveness as a preventative intervention remain a concern.  To name the most important examples, levels of risk-reduction were estimated as follows: CAPRISA 004 – 39%; iPrEX – 44%; CDC TDF2 – 62%; Partners-PrEP – 75%; FEM-PrEP – 0%; VOICE– 0%.  The reasons for this variation have been the topic of a number of contributions to this blog (especially: STI/blogs/Hendrix & Bumpus; STI/blogs/Haberer & Bangsberg), with consensus tending towards the poor adherence of study participants.

Last week in Cape Town results were briefly reported from a sub-study (VOICE D) of one of the less successful of these trials (VOICE). Microbicide Trials Network’s (MTN) VOICE study, discontinued in 2011, trialled daily tenofovir, in the form of vaginal gel or tablet, in 5,029 (mostly young) women from a representative range of sub-Saharan countries – S. Africa, Zimbabwe and Uganda. On the basis of self-reporting measures in the original VOICE trial, levels of adherence to the tenofovir regime had been estimated at 90%.  However, blood samples taken from participants found evidence of the drug in less of a third of the participants in the tablet arm, and less of a quarter of the participants in the gel arm, of the study.

After the closure of the VOICE study itself, the sub-study, VOICE D, engaged 127 former VOICE participants in in-depth interviews at which they were challenged with evidence of their poor adherence – with a view to stimulating frank discussion. When confronted with the evidence of blood tests, poor adherers initially expressed surprise and disbelief. Yet, according to the report, the aim of engaging frank discussion would seem to have been met.  The reason most frequently given was fear of the side effects of the drug, fuelled by peer participants and relatives and by the negative attitudes of community members.

Current trials of PrEP have re-evaluated and strengthened efforts to enhance adherence in the light of previous failures.  These include: the Follow-on African Consortium for Tenofovir Studies’ FACTS 001 (tenofovir gel before and after sex), the MTN’s ASPIRE and the International Microbial Partnership’s Ring Study (both the latter of vaginal ring releasing the ARV drug dapivirine) (MTN Trials). It is interesting that the Partners-PrEP study incorporated intensive “adherence interventions” for participants whose adherence levels fell below 80% (STI/blogs/Haberer & Bangsberg).

However, the VOICE D results may have implications for the usefulness of PrEP interventions more generally. At the very least, they discredit any idea that PrEP is able to offer a panacea. The value of PrEP, relative to other preventative interventions, is a contentious issue.  STI/Mukandavire & Vickerman (2013), for example, conclude that a scale-up of condom use is in most circumstances likely to be more effective than PrEP, but that PrEP could have a specific application in the case of female sex workers. STI/Verguet & Walsh (2012) see a future for PrEP in sub-Saharan countries with high HIV prevalence and without circumcision practice, such as S. Africa.  STI/Ying & Barnabas (2013) see targeted PrEP as a cost-effective addition to ARV.

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