UK PROUD study to provide PrEP to all participants earlier than expected: planned follow-up to continue to two years

1 December 2014. Related: HIV prevention and transmission.

Simon Collins, HIV i-Base

On 16th October 2014, UK researchers announced an important change in the PROUD study. Because of an early result about the effectiveness of PrEP when used by gay men in the UK at high risk of HIV, all participants will be offered immediate treatment. [1]

PrEP was approved in the US in July 2012 and involves taking a daily pill (Truvada) to reduce the risk of catching HIV. Approval was based on results from two large international studies: the iPrEX study in about 2,499 gay men and the PARTNERS PrEP Study in more than 4758 heterosexuals. [2] For PrEP to become available in the UK, the NHS wanted additional data on cost-effectiveness in a UK population.

The PROUD study randomised 545 gay men (in a 1:1 ratio) to either immediate access to PrEP for two years or to waiting for 12 months before getting PrEP. All participants received advice, information and condoms to reduce the risk of HIV throughout the study. [3] This design avoided using a placebo pill and ensured all participants would receive the active drug for at least 12 months.

For the study to change in this way due to early efficacy results is especially impressive. It is also surprising because PROUD was a pilot study that was too small to show efficacy differences. The main aims were to firstly see whether people were interested enough in PrEP to take a daily pill, and secondly, whether this would change their level of risk.

The change in the study is based on a recommendation from an independent data monitoring committee (IDMC). When it became clear to this expert panel that the difference in infection rates was significant, they recommended amending the study design.

The effectiveness result may be because men in the study were at higher risk of HIV than was initially expected when the study was planned. A recent presentation of these risk factors for people entering the study was recently presented at the International AIDS Conference in July 2014. [4]

Although it may take several weeks for these changes to be put n place, all participants will now have the chance to use PrEP. Details about the different rates of HIV incidence in each group have not been included in the statement, but a full analysis of these data are due to be released early in 2015.

The PROUD study will continue to follow-up all participants for the full two years, to collect information about behaviour and risk, in order to look at longer-term issues relating to PrEP.

Comment

This decision by the PROUD study increases the urgency for the NHS to produce recommendations for PrEP access in the UK.

Earlier this month, the latest figures from Public Health England reported that incidence rates in gay men are still increasing. Current health programmes to reduce new infections are not effectively reaching the people at highest risk. The latest figures report that 3250 gay men were diagnosed HIV positive last year, including more than 450 men aged 15-24 and more than 1100 aged between 25-34. [5]

Based on results from the iPrEX study, including later follow-up, occasionally missing PrEP is still likely to provide good protection (estimated at more than 90% protection with 4 or more doses a week). Daily PrEP provides protection that approaches 100%. [6]

Following this announcement from the PROUD study, the DSMB for the French/Canadian IPERGAY study rapidy assessed their results. This revealed a similar early efficacy finding and similar desicion to terminate the conrol arm, offering all participants immediate PrEP (see artcila below).

IPERGAY uses an alternative schedule to daily PrEP that includes taking a double dose of PrEP at least two hours before sex (preferably the day before) and then at least two subsequent single doses every 24 hours afterwards. IPERGAY used a placebo study design that resulted in slow enrolment. [7]

References:

1. PROUD statement. PROUD study interim analysis finds pre-exposure 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)
2. FDA press release. Truvada approved to reduce the risk of sexually transmitted HIV in people who are not infected with the virus. (16 July 2012).
   http://www.fda.gov/ForConsumers/ByAudience/ForPatientAdvocates/HIVandAIDSActivities/ucm312264.htm
3. Examining the impact on gay men of using Pre-Exposure Prophylaxis (PrEP) – the PROUD Study.
   http://www.proud.mrc.ac.uk
4. Antonucci S et al. The UK PROUD PrEP Pilot Study: a baseline analysis. Poster abstract THPE197.
   http://pag.aids2014.org/abstracts.aspx?aid=7659
5. Public Health England. National HIV surveillance data tables, Table 7, (October 2014).
   https://www.gov.uk/government/statistics/hiv-data-tables
6. Grant RM et al. Results of the iPrEx open-label extension (iPrEx OLE) in men and transgender women who have sex with men: PrEP uptake, sexual practices, and HIV incidence. Oral late breaker abstract TUAC0105LB.
   http://pag.aids2014.org/abstracts.aspx?aid=11143
7. On demand antiretroviral pre-exposure prophylaxis for HIV infection in men who have sex with men (IPERGAY)
   http://clinicaltrials.gov/show/NCT01473472