CDC offers PrEP guidance
by Liz Highleyman
The federal Centers for Disease Control and Prevention issued new interim guidance last week for the use of pre-exposure prophylaxis, better known as PrEP, to prevent HIV infection among high-risk gay and bisexual men. The recommendations specify appropriate candidates and outline important cautions.
"It's good that the CDC issued the interim recommendations, as some physicians and other health care practitioners have not known what to say to patients about going on PrEP since the iPrEx findings were released," said Judith Auerbach, Ph.D., of the San Francisco AIDS Foundation.
As announced last November, the iPrEx study showed that daily oral tenofovir plus emtricitabine – the two drugs in the Truvada pill – can lower the risk of HIV acquisition when used in conjunction with other risk-reduction measures.
The Phase 3 trial included nearly 2,500 sexually active, HIV-negative men who have sex with men and a small number of transgender women in South America, South Africa, Thailand, and San Francisco and Boston in the U.S.
Participants, who had an average of 18 sex partners in the three months before enrollment and were judged to be at high risk for infection, were randomly assigned to take Truvada or an inactive placebo pill once daily. They also received free condoms, monthly HIV testing, and regular counseling about risk reduction and medication adherence.
During an average follow-up period of about one year, 36 people using Truvada PrEP were newly infected, compared with 64 people taking placebo – a risk reduction of 44 percent. Participants who took their drugs as directed most of the time lowered their risk by 73 percent. What's more, men in both groups reported more condom use and fewer sex partners.
The iPrEx trial results were greeted with enthusiasm, but they also raised numerous questions about who could potentially benefit, long-term drug side effects, and cost and access issues.
The Food and Drug Administration has not approved Truvada for HIV prevention, but some gay men are eager to start using it as PrEP right away. The recent CDC guidance is intended to offer temporary recommendations until public health agencies develop more definitive guidelines and other trials – including ongoing studies of different populations – provide additional data.
The guidance, published in the January 28 issue of "Morbidity and Mortality Weekly Report" and summarized on the CDC's website (www.cdc.gov/nchhstp/newsroom/PrEPMSMGuidanceGraphic.html), specifies that the iPrEx findings only support PrEP for gay and bisexual men with "substantial, ongoing, high risk" for acquiring HIV.
"This was a very select population, only men having sex with men, only ones with multiple sex partners engaging in continued high risk behavior," said Dr. Michael Horberg, director of HIV/AIDS at Kaiser Permanente and vice chair of the HIV Medicine Association. "We have to be careful thinking this applies to any other people than that specific population – we just don't have the data."
"At this time, the findings cannot be applied to monogamous serodiscordant [gay male] couples," he added. "It does not apply to people who just want to take a pill on Saturday night, nor to [serodiscordant] heterosexual couples where the woman wants to get pregnant."
Prospective users must be tested for HIV before starting PrEP and every two to three months thereafter, since using Truvada without other antiretroviral drugs if HIV is present can lead to drug resistance. They should also be tested for hepatitis B and other sexually transmitted diseases.
People with flu-like symptoms that could indicate acute or very early HIV infection need special testing because they may not yet have enough antibodies to show up on a standard screening test.
In addition, kidney function should be checked before starting PrEP and monitored regularly, since tenofovir can cause kidney problems in susceptible people.
"PrEP should be done by an HIV or infectious disease specialist care team," said Horberg. "This is a complex protocol and follow-up that is best done by people who have a lot of experience."
Just one tool
The CDC guidance also emphasizes that PrEP recipients should receive regular risk-reduction counseling and condoms, as well as support around medication adherence, as was done in the iPrEx trial.
"[PrEP] was not an either/or, it was a both/and," Horberg stressed. "This [study] was an affirmation of more traditional prevention – it did in fact show that even control patients who did not get the medication had more protected sex and lower risk."
"This is one tool along with a number of other different tools to help men who have sex with men remain HIV-negative," concurred Dr. Brad Hare, medical director of the Positive Health Program at San Francisco General Hospital. "The same guidance remains regarding condom use, learning your HIV status, and practicing safer sex. These things are still relevant in the era of PrEP."
Hare noted that many local health departments have been "struggling" with how to implement PrEP in the wake of the iPrEx findings. "Here in San Francisco, our health department has been on the front of the wave and has already begun figuring out how this is relevant," he said. "The guidance will help refine what to do."
"It's very important to be prepared for a likely PrEP roll-out in communities like San Francisco, given the strength of the iPrEx data," added Auerbach. "This is why a number of us are advocating for a demonstration project that will assess the desirability and feasibility of PrEP as a component of the city's HIV prevention strategy."