- Category: Approved HIV Drugs
- Published on Wednesday, 30 May 2012 00:00
- Written by Liz Highleyman
The U.S. Food and Drug Administration (FDA) recently approved new product label information for raltegravir (Isentress), adding longer-term data showing that the drug remains effective for more than 3 years. In related news, researchers reported that raltegravir appears to be a good option for post-exposure prophylaxis (PEP) to prevent HIV infection.
Raltegravir, the sole HIV integrase inhibitor, was shown to be safe and well-tolerated in pivotal clinical trials. In real-world use, it has provided an urgently needed "rescue" option for heavily treatment-experienced patients with highly resistant virus, as well as a therapy with few side effects for treatment-naive people.
Manufacturer Merck last week announced that the FDA approved a labeling update to include 156-week datafrom the Phase 3 STARTMRK trial, which compared 400 mg twice-daily raltegravir against the widely-used once-daily NNRTI efavirenz (Sustiva), both in combination with tenofovir/emtricitabine (the drugs in Truvada), in 563 previously untreated HIV positive adults.
At 48 weeks (the primary endpoint), raltegravir was shown to be non-inferior to efavirenz, with 86% and 82% of participants in the 2 arms, respectively, achieving HIV RNA < 50 copies/mL.
The 156-week analysis showed continued long-term viral suppression, with 76% of raltegravir recipients and 68% of efavirenz recipients maintaining undetectable viral load. People on raltegravir had a larger mean CD4 cell gain at 156 weeks, +281 vs +241 cells/mm3.
Patients taking raltegravir were less likely than those on efavirenz to discontinue treatment due to clinical adverse events (5% vs 9%, respectively, by week 156), with the most notable reduction in neuropsychiatric side effects. Raltegravir recipients also had smaller changes in blood lipid levels.
Raltegravir for PEP
As described in the April 1, 2012, Journal of Acquired Immune Deficiency Syndromes, Kenneth Mayer and colleagues at Fenway Health in Boston evaluated a 3-drug regimen of raltegravir, tenofovir, and emtricitabine used as "morning after" prevention after high-risk sexual exposure.
The study included 100 HIV negative people who visited the clinic within 72 hours after a potential sexual exposure to HIV, including anal, vaginal, oral, or other mucosal exposure to semen, cervicovaginal secretions, or rectal secretions from a known HIV positive partner or a high-risk partner of unknown status. All but 2 were men, 76% were white, and the average age was 33 years.
Most participants (83%) were men who had sex with men, 10 identified as bisexual, and 5 identified as heterosexual. About one-third said they knew they had sex with an HIV positive partner; 57% reported unprotected anal sex, with insertive sex being twice as common as receptive sex (42% vs 21%).
Among the 85 participants with evaluable data at 3 months, none were infected with HIV. Pill counts were performed at 14 and 28 days; 57% completed the regimen as prescribed, while 27% said they took medication daily but sometimes missed the second daily dose of raltegravir -- a potential disadvantage relative to a completely once-daily efavirenz/tenofovir/emtricitabine regimen.
The most frequently reported side effects included nausea or vomiting (27%), diarrhea (21%), headache (15%), fatigue (14%), abdominal symptoms (e.g., pain, gas, or bloating; 16%), and muscle or joint pain (8%). Symptoms were mild and did not lead to drug discontinuation. Adverse events rates were significantly lower than those historically reported by people using zidovudine/lamivudine (AZT/3TC) plus a ritonavir-boosted protease inhibitor for PEP.
"Raltegravir, tenofovir DF, and emtricitabine may be useful as a 3-drug regimen for PEP," the researchers concluded. "The study was not powered to demonstrate efficacy for HIV prevention, but the lack of incident HIV infections and high level of tolerability for [raltegravir] in high-risk HIV-uninfected participants when used in combination with tenofovir DF-emtricitabine was reassuring."
"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," they added in their discussion.
Merck. FDA Approves New Labeling for ISENTRESS (raltegravir) to Include 156-Week Data Demonstrating Long-Term Efficacy, Safety and Tolerability with ISENTRESS in Combination Therapy in Previously Untreated Adult Patients Infected with HIV-1. Press release. May 21, 2012.
KH Mayer, MJ Mimiaga, M Gelman, C Grasso, et al. Raltegravir, Tenofovir DF, and Emtricitabine for Postexposure Prophylaxis to Prevent the Sexual Transmission of HIV: Safety, Tolerability, and Adherence. Journal of Acquired Immune Deficiency Syndromes 59(4):354-359. April 1, 2012.