Tag Archives: AIDS Vaccine Advocacy Coalition

US Regulators Vote For Approval of PrEP by Large Majority

The US Food and Drug Administration (FDA) took a decisive step yesterday towards approving the use of combination pill Truvada(tenofovir/FTC) as a prevention method for HIV-negative people.

The FDA’s Antiviral Drugs Advisory Committee (ADAC) voted by a majority of 19 to 3 in favour of recommending Truvada as PrEP (pre-exposure prophylaxis) for men who have sex with men, and by 19 to 2 with one abstention for an approval for use by the HIV-negative partner in serodiscordant couples.

There was a close vote, however, when it came to recommending its use generally in individuals for people at risk of HIV infection: 12 to 8, with two abstentions, voted for a general recommendation for any person at risk of HIV.

The ADAC decision was taken after an all-day meeting on 10 May. This meeting discussed the findings of a written report and also heard submissions from a large number of community prevention and treatment advocates. Interest was such that the FDA extended the time for submissions from advocates and community members from one hour to two and had to organise a ballot for access to the hearings.

The written report had concluded that concerns about safety and HIV drug resistance were not sufficient to delay the introduction of PrEP. It also decided that concerns about poor adherence levels seen in some randomised controlled trials, and about whether PrEP would negatively influence behaviour to such a degree that people ended up at greater risk of HIV, were beyond the remit of the FDA.

“I don’t think it’s our charge to judge whether people will take the medicine,” panellist Dr Tom Giordano told the Los Angeles Times. “Our charge is to judge whether it works when taken.”

Considerations of cost are also explicitly ruled out of the FDA’s remit when it comes to approving a new drug or indication.

The FDA is not bound to follow the recommendations of its advisory committees and will make a final decision by 15 June. However it is very rare for it not to do so and the large majority in favour of its approval for gay men and in serodiscordant couples makes this unlikely.

PrEP has always excited controversy amongst HIV prevention advocates and people affected by HIV. Some organisations have opposed its introduction and the AIDS Healthcare Foundation, in particular, has mounted a provocative campaign against its approval. “If you love Vioxx you’ll love PrEP,” read one poster displayed on bus shelters near the White House, referring to the painkilling drug that was withdrawn in 2004 when it was linked to heart attacks.

The majority of HIV prevention advocates, however, has supported PrEP. Mitchell Warren of the AIDS Vaccine Advocacy Coalition (AVAC) commented: “Some funders and policy makers have been awaiting a signal from the FDA before launching demonstration projects or developing implementation plans.

“The time for waiting is over. We need to get on with the work of setting priorities and rolling out PrEP to people who can benefit the most.”
The controversy was if anything reinforced when the randomised controlled trials (RCTs) of PrEP that have reported in the last 18 months –iPrEX, Fem-PrEP, Partners PrEP and TDF2 – produced strikingly different results, with headline efficacy levels ranging from zero (in Fem-PrEP) to 83% (for men in Partners PrEP). Studies of drug levels found that these results could be explained by different levels of adherence in trial participants. PrEP was 92% efficacious in participants in iPrEx who had detectable levels of drug in their blood, and it is clear that adherence levels will crucially determine whether it protects the people who take it.

At present randomised controlled trials have only tested daily doses of PrEP, though a study in France, IPERGAY, is currently testing its efficacy in gay men when taken on a before-and-after-sex basis.
In contrast concerns about negative behaviour change and participants putting themselves at greater risk of HIV have not been supported by RCT findings, but it is recognised that these will only be answered by an open-label study in which people know for sure that they are taking the drug and not a placebo.

Such a study, called PROUD, has been suggested for the UK and is awaiting a decision on approval. In this study gay men attending genitoruinary medicine clinics in the UK who are at significant risk of HIV will be offered TruvadaPrEP plus a package of behavioural support and counselling, but will be randomised to receive the PrEP component either immediately or a year later.

Principal Investigator of the proposed study, Dr Sheena McCormack of the UK Medical Research Council (MRC), told Aidsmap: “It is unusual for the MRC to talk publicly about a trial before it receives approval, but in the case of PrEP it is so important that the trial involves and is supported by its target community.”

Original article by Gus Cairns at Nam

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HIV drug-prevention strategy carries risks [PrEP]

Earlier this month, we posted a video containing data from the iPrEx trial from the IAS 2011 conference stating that tenofovir/emtricitabine (Truvada) reduced new HIV infections by 42% overall, and by more than 90% among people who demonstrated good adherence.

When the US Food and Drug Administration approved Viagra in 1998, officials never considered one possible side effect of the drug: higher rates of sexually transmitted diseases among men who, thanks to Viagra, would become more sexually active. A powerful tool in the fight against HIV is raising similar questions about the possibility of unintended public-health consequences if drugs are approved for use in healthy people and cause them to alter their behaviour.

Several studies in the past year have reported that the very drugs used to treat people with HIV can also stop healthy people from becoming infected (see table below).

People taking the drugs may adopt riskier behaviours because they feel protected — a phenomenon known as ‘risk disinhibition’ — undermining the benefit of the drugs and potentially infecting others. Moreover, those who become infected while taking the preventive regimen might develop drug-resistant viruses that they could then transmit to others. “You have this wonderful scientific breakthrough,” says Kevin Frost, chief executive of the Foundation for AIDS Research in New York City. “But what are the practical implications?”

Researchers will mull over these issues today at a meeting convened by the Forum for Collaborative HIV Research in Washington DC. The questions have become more urgent since January, when the drug firm Gilead of Foster City, California, announced that it plans this year to ask the Food and Drug Administration (FDA) to approve its HIV drug Truvada for use in healthy people — in what is known as pre-exposure prophylaxis, or PrEP. Truvada, which contains the antiretroviral drugs tenofovir and emtricitabine, has been used in many of the PrEP trials. In the three clinical trials that have reported benefits for PrEP so far, once-a-day pills have cut a person’s risk of acquiring HIV by between 44% and 73%, a variation that is due primarily to differences in how strictly patients stuck to the daily regimen.

Asking the FDA to evaluate questions about risk disinhibition and drug resistance might push the agency into uncharted territory. “When you’re talking about a population issue, is that something that the FDA should be looking at at all?” asks Jur Strobos, deputy director of the Forum for Collaborative HIV Research.

The clinical trials don’t offer clear guidance. Some of the successful trials found that people on PrEP actually used condoms more frequently while receiving PrEP treatment, countering the risk-disinhibition argument. And only a few instances of drug resistance occurred, and these did not compromise patients’ treatments.

But the controlled setting of a clinical trial, in which participants received intensive prevention counselling and were tested monthly for HIV, is very different from the real world. “We think of PrEP as a pill, but we all recognize that PrEP is about a much broader programme,” says Mitchell Warren, director of the AIDS Vaccine Advocacy Coalition in New York City. “How you would deliver the kind of testing and monitoring that would go into that programme is a very important question.”

The US Centers for Disease Control and Prevention (CDC) has recommended testing patients for HIV before they begin taking the drugs and again at two- to three-month intervals. The FDA could also require drug companies to set up a registry of patients taking the drugs and ask that patients provide proof of a negative HIV test before getting their medications refilled.

Deciding who to treat with PrEP could also be a challenge. The CDC reported on 3 August that rates of new HIV infection in the United States are stable overall, but are rising in young men who have sex with men. Yet if these men aren’t using the prevention measures already available, there’s little reason to think doctors will have an easier time convincing them to take a daily pill.

The question of who should get PrEP is more difficult in many developing nations, which cannot even afford to treat everyone currently infected with HIV. PrEP would cost hundreds of dollars per patient per year in developing countries, and many thousands of dollars in rich nations.

Even with regimens costing less than £1 per day, developing nations will be forced to choose between providing more treatment for those who already need it and potentially preventing new infections. Myron Cohen, a doctor and researcher at the University of North Carolina at Chapel Hill, points out that half of young girls in some parts of sub-Saharan Africa become infected with HIV by their mid-twenties. “That’s unacceptable, so I see that as one potential population for PrEP,” says Cohen.

Although the cost-effectiveness of PrEP increases in higher-risk populations, it will be politically dicey for financially strapped countries to justify distributing drugs to those in these groups. “Even if you thought the best use of the pills would be for sex workers, it would be very difficult to take a limited supply of pills and give them to high-risk populations at the expense of people who are dying of infection,” says Cohen.

Original Article written by Erika Check Hayden at Nature.com

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