IPERGAY PrEP study shows early efficacy in protecting gay men from HIV: all participants to switch to active drug

1 December 2014. Related: HIV prevention and transmission.

Simon Collins, HIV i-Base

On 29 October 2014, French and Canadian researchers announced early efficacy of a PrEP study to protect gay men from catching HIV. This has led to a change in the study design. [1]

If taken daily, Truvada provides close to 100% protection against HIV.

The IPERGAY study is being run at six hospitals in France and one site in Canada. Participants in the placebo arm of the study will now be offered active PrEP.

This decision was based on a safety assessment mid-way through the study, prompted by news that a UK PrEP study called PROUD had made similar changes a few weeks earlier, also based on unexpected early efficacy. [2]

The early results in IPERGAY and PROUD are likely to be related to a combination of the participants being at high risk of HIV and having good adherence to treatment.

However, both studies have only released the top-line decision to make PrEP available to all participants. This limits further discussion about either the detailed results or why PrEP was so effective. Full analyses are being prioritised but are still likely to take several months.

The full analysis is especially important for IPERGAY as it uses an experimental dosing. The study press statement does not include details of whether infections still occurred using this dosing or how effective it is compared to daily dosing.

Although a daily pill was approved in the US in July 2012 to reduce the risk of catching HIV, earlier PrEP studies found conflicting results. These larger PrEP studies faced two main challenges. The first was to enrol people who were at genuinely high risk of catching HIV and who continued to be at high risk during the study. In the absence of risk, even the most effective intervention will be unable to prove a benefit. The second challenge, also considerable, was dependent on people at risk actually taking the prescribed pill (or placebo).

Some studies, despite finding PrEP effective, involved following thousands of participants for several years, to only avert relatively few infections.

Other studies, also large and carefully designed, reported no benefit largely due to low adherence.

Differences between IPERGAY and PROUD

IPERGAY and PROUD have very different study designs.

Although the IPERGAY dosing schedule is referred to as “on demand” it includes the need to take the first PrEP dose 2-24 hours before sex. This requires a degree of planning or forethought (but there is no safety concern if the pre-dose was optimistic and sex does not occur).

Dosing continues as long as the person is sexually active, although not taking more than one dose every 24 hours. This is completed with a pill after sex and the final tablet 24 hours after this.

IPERGAY also uses a placebo design. This meant that half the participants used the real drug and half used an inactive dummy tablet. Participants, doctors and researchers did not know who was getting the real drug.

PROUD uses a daily dosing schedule. Participants were asked to take a single pill every day, whether or not they were sexually active. This study did not use a placebo but compared immediate PrEP to deferred PrEP. Half the participants in this study used PrEP from the beginning of the study and half were due to start after 12 months. All participants received health advice and condoms and kept a diary of sexual activity in order to look at whether PrEP affects behaviour risk.

The PROUD study announced on 16 October 2014 that all participants were going to be offered immediate PrEP because of significant and unexpected differences in HIV rates in the two groups. [3]

For further information there is a non-technical leaflet about PrEP and the PROUD study, produced by i-Base. [4]

Comment

Although both IPERGAY and PROUD have amended their initial study designs, both continue as active studies. This continued follow up is essential.

Although the IPERGAY researchers state that they have found efficacy to be much higher than the iPrEX study, this needs to be interpreted cautiously until the full analysis is available. The statement was apparently made in reference to the 42% effect in iPrEX overall rather than the 99% risk reduction in people taking daily PrEP. It is also important not to interpret the IPERGAY statement as implying that the IPERGAY dosing schedule is more effective than that used in iPrEX.

Background rates of HIV and adherence might make the relative results between the two groups in the IPERGAY study higher than relative rates between groups in iPrEX study, but this doesn’t make it more effective.

The early announcement about the IPERGAY study also risks an interpretation that the IPERGAY dosing schedule is more effective than daily dosing in iPrEX. The reduced dosing schedule used in IPERGAY is still being investigated and until these data are available, daily dosing remains the optimal way to use PrEP.

Reference:

1. IPERGAY press statement. Un grand success dans la lutte contra le VIH./SIDA. Un médicament pris au moment des rapports sexuels réduit efficacement le risque d’infection. (29 October 2014).
   http://www.ipergay.fr 
Press release (English version) IPERGAY October 2014 (Word.doc)
2. PROUD press statement. PROUD study interim analysis finds pre-exposue prophylaxis (PrEP) is highly protective against HIV for gay men and other men who have sex with men in the UK. (16 October 2014).
   http://www.proud.mrc.ac.uk/PDF/PROUD%20Statement%20161014.pdf (PDF)
   http://www.proud.mrc.ac.uk
3. Collins S. UK PROUD study to provide PrEP earlier than expected: planned follow-up in this HIV prevention study to continue for two years. (16 October 2014).
   https://i-base.info/uk-proud-study-to-provide-prep-earlier-than-expected
4. Q&A on PrEP in the UK and changes to the HIV PROUD study.
   https://i-base.info/qa-on-prep-in-the-uk-and-changes-to-the-hiv-proud-study