April 12, 2012
Isentress Plus Truvada Is Safe, Potentially Effective as HIV PEP Regimen
by Tim Horn
Isentress (raltegravir) combined with Truvada (tenofovir plus emtricitabine) was “extremely well tolerated” as post-exposure prophylaxis (PEP) following high-risk sexual activity in a small study conducted by a team of researchers at Fenway Health in Boston.
Though the study published in the April 1 issue of the Journal of Acquired Immune Deficiency Syndromes (JAIDS) wasn’t designed to make comparisons with currently preferred PEP regimens, “the data suggest that the addition of raltegravir did not result in an increase in adverse events and that tenofovir-containing regimens seemed to be better tolerated than three-drug regimens containing zidovudine and a protease inhibitor.”
National PEP guidelines, for those potentially exposed to the virus via occupational and non-occupational routes (for example, through sex), were last updated in 2005. According to Paul Sax, MD, editor-in-chief of Journal Watch HIV/AIDS Clinical Care and clinical director of the HIV Program and Division of Infectious Diseases at Brigham and Women’s Hospital, the guidelines are currently being updated.
The current non-occupational PEP guidelines list Atripla, Sustiva plus Combivir, and Kaletra plus Combivir as preferred antiretroviral (ARV) regimens for PEP—all three options are three-drug regimens—started within 72 hours of possible exposure and continued for four weeks. The occupational PEP guidelines are somewhat vague in their preferred regimens, and they generally favor two-drug combinations (notably those involving nucleoside reverse transcriptase inhibitors), with three-drug regimens recommended when the source is known to be living with HIV.
“The main arguments in favor of a two-drug PEP regimen have been improved tolerance and simplicity, which positively correlated with improved medical adherence and likelihood of completing the prescribed regimen,” Kenneth Mayer, MD, of Fenway Health and his colleagues wrote. “However, a simple well-tolerated and effective three-drug [non-occupational] PEP regimen could obviate the need to make difficult (and potentially arbitrary) decisions between using two drugs or three drugs for PEP.
The study conducted by Mayer and his colleagues is the first to evaluate an integrase inhibitor, Isentress, as the third active agent in a PEP regimen. “The rationale was based on the findings that this drug has been shown to be extremely well tolerated, with potential antiretroviral activity, and three-drug regimens are most likely to be most efficacious in preventing HIV transmission if they are well tolerated.”
More specifically, Mayer’s team noted that “the use of an integrase inhibitor makes great sense for HIV prevention because these compounds prevent HIV from becoming established in latent reservoirs of susceptible cells, inhibiting a different cellular target than the reverse transcriptase inhibitors most commonly used for PEP.”
The study was conducted at Fenway Health, where there has been a comprehensive PEP program for more than a decade. One hundred study volunteers potentially exposed to HIV were enrolled, 98 of whom were male. Most (83 percent) were men who had sex with men; 10 identified as bisexual and five as heterosexual. The average age of the participants was 33, and 76 percent were white.
More than one-third of the participants indicated that they knew they were exposed to an HIV-positive partner. Fifty-seven percent reported unprotected anal sex, either because of not using condoms or because of condom breakage; 21 percent reported known exposure to ejaculate.
Eighty-five of the 100 volunteers received follow-up testing after three months, and none became infected.
The most commonly reported symptoms among the volunteers receiving Isentress plus Truvada were nausea and/or vomiting (27 percent); diarrhea (21 percent); headache (15 percent); fatigue (14 percent); abdominal discomfort, including pain, gas or bloating (16 percent); and/or bone or muscle pain (8 percent).
Fifty-seven percent of those enrolled completed the four-week regimen—Isentress taken twice a day and Truvada taken once a day—as prescribed. Twenty-seven percent completed a modified regimen. The most common modification of the regimen was failure to consistently take the second daily dose of Isentress, but all these participants reported adherence to the daily use of the Truvada dose
“The completion rates of this regimen were comparable with that of historical controls who took [Truvada] alone, and were superior to the completion rates of those who used [Combivir] and a protease inhibitor,” Mayer and his fellow authors wrote.
“The study was not powered to demonstrate efficacy for HIV prevention, but the lack of incident HIV infections and high level of tolerability for this drug in high-risk HIV-uninfected participants when used in combination with [Truvada] was reassuring,” the researchers concluded. “Other studies are underway evaluating the use of integrase inhibitors as a topical microbicide alone and coformulated with other antiretroviral drugs, and other integrase inhibitors are currently being studied for therapeutic use, so the optimal ways in which this potent new class of antiretroviral agents could be used to prevent HIV transmission will take some time to elucidate. However, the current study provides some new data to suggest that [Isentress] should be considered as a useful third drug for post-exposure chemoprophylaxis.”
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