The road to PrEP: trials, regulation and roll-out

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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 placebo-controlled trials.

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.  



A clinical trial where both the researcher and participants know who is taking the experimental treatment. 

European Medicines Agency (EMA)

Regulatory agency that evaluates medicines for safety and efficacy in Europe, performing a similar role to the Food and Drug Administration (FDA) in the United States. The EMA recommends to the European Commission that a medicine can be marketed in the European Union and European Economic Area.

Food and Drug Administration (FDA)

Regulatory agency that evaluates and approves medicines and medical devices for safety and efficacy in the United States. The FDA regulates over-the-counter and prescription drugs, including generic drugs. The European Medicines Agency performs a similar role in the European Union.


A pill or liquid which looks and tastes exactly like a real drug, but contains no active substance.


In relation to medicines, a drug manufactured and sold without a brand name, in situations where the original manufacturer’s patent has expired or is not enforced. Generic drugs contain the same active ingredients as branded drugs, and have comparable strength, safety, efficacy and quality.

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 to 18.

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 for treatment.

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 over 90%.

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.

Further information

See for slides presented at the IAPAC evidence summit, Controlling the HIV epidemic with antiretrovirals.