Ask a Guinea Pig: What Do I Need to Know Before Joining a PrEP Trial?
Editor’s note: For folks considering joining a study and helping advance HIV treatment, prevention, or cure research, today we launch “Ask a Guinea Pig,” BETA’s new quarterly column and your frank and honest resource on the pros and cons of taking part in clinical trials. Columnist Matt Sharp is himself a veteran of many HIV-related studies (see for yourself in his fascinating first-hand account of a gene therapy trial). Have a question for Matt? Post a comment below, and your question could be addressed in the next column.
I’m interested in entering a PrEP trial but I have concerns about the risks. What happens if I test positive during the trial? How safe is Truvada if I’m not using it for treatment? And will there be trials to see whether you can take PrEP other than once a day?
In the last few months there has been a lot of talk—and lots of questions—about PrEP, or pre-exposure prophylaxis. PrEP is a new approach to HIV prevention in which HIV-negative people take antiretroviral drugs—some of the same drugs HIV-positive people take to manage their HIV disease—to avoid acquiring the virus.
On May 10, I was a member of the U.S. Food and Drug Administration (FDA) Advisory Committee that recommended approval of Truvada—a combination of two antiretroviral drugs, tenofovir (Viread) and emtricitabine (Emtriva)—for HIV prevention. The FDA is expected to approve Truvada for PrEP by this fall (an announcement of the decision is anticipated on September 14). [Update: The FDA approved Truvada for PrEP on July 16, 2012.]
The advisory panel reviewed data from major PrEP studies and heard public testimony from over 40 people in the marathon 13-hour meeting (webcasts are available here), yet there is still much that isn’t clear about the best way to use PrEP. However, more randomized trials and smaller demonstration projects are underway that will hopefully characterize the best way to use this new prevention tool.
One key concern is what will happen if people seroconvert (become infected with HIV) while using PrEP. Truvada offers only part of a full HIV treatment regimen and can’t fully suppress the virus on its own; at least one more drug is needed to keep the virus from making more copies of itself and possibly developing resistance to HIV meds. Does that mean that anyone who does acquire HIV while on PrEP will end up with drug-resistant virus?
It’s a legitimate question, but no clinically significant development of drug resistance has been seen in people who seroconverted while taking PrEP in a clinical trial. The fact is that transmission rates are very low in most PrEP studies so far. Those who were randomized to receive Truvada—and took the pills as directed—were significantly less likely to become infected. Participants in these studies are regularly tested for HIV, provided with free condoms, and counseled on safer sex. People who test positive are immediately offered treatment. New and ongoing studies will help shed light on ways to use PrEP in the real world. The FDA panel agreed that condoms should not be thrown away when using Truvada for PrEP.
About safety: Truvada was generally safe in the PrEP clinical trials reviewed by the FDA panel. However, there are predictors of kidney function decline with people who have used Truvada in the past. Risk factors include older age, low body weight, lower creatinine clearance (indicating existing kidney problems), type 2 diabetes, hypertension (high blood pressure), hepatitis C infection, and use of other drugs that put a strain on the kidneys. People who use Truvada for PrEP will be screened for these predictors before they take it.
What’s next for dosing options? Studies are ongoing to look at other doses of PrEP, as taking a pill every single day may be challenging for some people. Most trials of Truvada PrEP study once-daily dosing, the same as used in HIV treatment. This is because the levels of the drug in the blood stay the same over time if the drug is taken once a day. One trial in Cape Town and Bangkok is now looking at intermittent Truvada dosing, and other trials using other drugs will assess different dosing schedules as well as intramuscular injections.
Despite pending approval, there is still much to learn about Truvada for PrEP, which is why new trials and demonstration projects are so important. I liken this to how AZT, the first-ever effective treatment option for people with HIV, was first studied and rolled out to the public, then further assessed as more trials, newer drugs, and other strategies became available. Until there is a perfect biomedical intervention, Truvada for PrEP will only be the beginning.
Matt Sharp is a Person with AIDS, longtime HIV treatment advocate, and writer.
From the Fenway Institute: Policy Focus—Pre-Exposure Prophylaxis for HIV Prevention: Moving Toward Implementation
From San Francisco AIDS Foundation: HIVResource: A Guide to Clinical Research in the San Francisco Bay Area