Within the next three years, up to 33,000 people may take part in 22 different studies worldwide to
demonstrate the feasibility, or otherwise, of pre-exposure prophylaxis (PrEP)
to prevent HIV, the IAPAC evidence summit, Controlling the HIV epidemic with antiretrovirals, was told on 12
June.Some of these studies are underway but others are still in the design stage or in need of funding.
Dr Jim Rooney of Gilead Sciences, the manufacturer of tenofovir (Viread) and Truvada (tenofovir and FTC), the products being tested in the vast majority of these studies, told the meeting that up to
13,000 men who have sex with men (MSM) could end up being involved in 14
different studies and up to 19,500 heterosexual men and women in eight studies.
These studies were particularly crucial in establishing whether PrEP might be
less, or more, effective in open-label settings than in randomised
Some of these are ongoing or open-label extensions of studies
such as Partners
PrEP in 4758 sero-different couples in Kenya and Uganda, or iPrEx OLE (Open Label Extension) in 1500
MSM in six countries.
Others are just beginning, such as the IPERGAY study of intermittent PrEP in gay men
in France. While it is planned that this could eventually include 1900 men,
researcher Bruno Spire told the IAPAC meeting that 300 participants had to be
enrolled by February 2013 if the next phase of the study was to be funded, and
that recruitment had been rather slow so far, partly because of "ideological
obstacles" to there being a placebo arm.
Similarly, Dr Sheena McCormack of the UK's Medical Research
Council told the meeting that, while the planned UK PROUD study of immediate
versus delayed PrEP could eventually include 5000 MSM, only a pilot project in
300 MSM has so far been proposed, with a tentative start date (if the protocol
is agreed) in October 2012.
In the US, nine studies in 4255 MSM are planned; these include
specific studies amongst African-Americans and adolescents. In the latter case,
a study amongst 18- to 22-year-olds is ongoing, with a possible extension to 15- to
17-year-olds. Similarly in South Africa,
a small study called CHAMPS will recruit 100 male and female teenagers aged 14
Also in South Africa, a second
– or rather third
– study of a
vaginal microbicide, FACTS, will recruit 2200 women aged 18 to 30 and possibly
another 400 aged 30 to 40. The study will aim to confirm the efficacy demonstrated
in the CAPRISA
004 study, after the
failure of the tenofovir-gel arm of the VOICE study to do that. A smaller study will look at safety and
acceptability in 15- to 17-year-olds.
Jim Rooney also looked at the regulatory environment. The US
Food and Drug Administration voted for approval of tenofovir/FTC (Truvada) as PrEP in May this year but
confirmation, expected in September, is subject to a Risk Evaluation and
Mitigation Strategy (REMS) document. In Europe, Rooney said, Gilead had been in
talks with the European Medicines Agency (EMA) but specific plans for
authorisation had not been finalised and at present the EMA has issued a draft
of a so-called ‘reflection paper’ on the general requirements for licensing HIV
drugs for prevention: comments
and feedback are welcome until 30 June.
Rooney said that plans were in place to file for authorisation in Africa, Latin
America and Asia following the FDA review. He shared what the wording of an
indication for PrEP might look like and added that there would be specific
warnings on the need to use Truvada
in combination with other prevention methods, that a negative HIV test was
essential before it was prescribed as PrEP, and that good adherence was
essential. There would not be a different, prevention-specific formulation of Truvada (this had been suggested in some
quarters as a way to avoid informal use) and Gilead would support the
manufacture of generic versions of PrEP for resource-poor locations, as it does
Gilead was prepared to work with PEPFAR, the Global Fund and
the World Health Organization, but so far no decisions had been taken about PrEP
roll-out in lower-income settings, Rooney said, and added that Gilead was
drafting educational materials for potential users of PrEP.
As for future PrEP developments, Jim Rooney said that
Gilead was studying the PrEP potential of its new prodrug of tenofovir GS 7340,
and even of drugs that could be specifically used for prevention: trials were
already underway or beginning of the entry inhibitor maraviroc (Celsentri) plus or minus
tenofovir and/or FTC, as PrEP.
During the question time in the session, Jorge Saavedra, ex-HIV prevention
director for Mexico and now at the AIDS Healthcare Foundation,
which has opposed the development of PrEP, questioned why adherence would be
better in clinical conditions than in CTs. Rooney pointed out that in some
settings, such as the American sites of the iPrEx trial, adherence had been
Several questioners were concerned about resource allocation,
given that only a minority of people with HIV are actually on treatment, even
in the US. Helen Rees, lead investigator in FACTS, commented: “Probably, the
elephant in the room is prevention versus treatment in resource-constrained
settings. We have a public health dilemma. Personally I feel an incrementally
growing use of treatment as prevention over a period of time is going to be
easier than introducing PrEP.”
She did, however,
support pilot studies: “There may be groups that are easier to reach such as
pregnant women, and more people may come forward for PrEP because of fear of
the stigma of testing HIV positive.”
Ron d’Amico of drug company Abbott commented that
pharmacovigilance (the monitoring of drugs for adverse effects) would be even
more stretched in places like Africa than it already is if use of generic PrEP
started to be widespread: who would be charged with the task of monitoring?
Manuel Gonçalves of ViiV Healthcare, the Pfizer/GSK HIV drug
partnership, commented on the ethical minefield of offering PrEP to subjects in
countries where it was not available to all for treatment, and of the fact that
“people who need PrEP the most and in whom most of the trials were done will be
the last to get it”. He commented that this was the same situation that was
seen in HIV treatment in the 1990s and should not be allowed to happen again.