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Alternatives to Protease Inhibitors for HIV Treatment

Non-nucleoside reverse transcriptase inhibitors, although not without their own problems, now are favored for initial HIV treatment.

In the late 1990s, AIDS mortality rates were sent plummeting by combination drug regimens consisting of a protease inhibitor (PI) and two nucleoside reverse transcriptase inhibitors (NRTIs). However, a third family of antiretroviral drugs, the non-nucleoside reverse transcriptase inhibitors (NNRTIs) might bring just as much power to combination regimens as did the protease inhibitors without some of their disadvantages, which include stringent dosing schedules and frequent side effects.

In an open-label, manufacturer-supported study, an international consortium of researchers randomized 1216 treatment-naïve HIV-positive men and women to combination treatment that consisted of the NRTIs stavudine and lamivudine along with one or two NNRTIs (nevirapine once or twice daily, efavirenz, or both drugs). The group that received both NNRTIs had higher rates of drug toxicity, but the other groups had similarly high rates of virologic suppression (63%-70% at week 48) and median increases in CD4 counts (160-170 cells), which are comparable to results from PI-based regimens.

In a second study, U.S. researchers randomized 1147 treatment-naïve HIV-positive people to a combination of three NRTIs only, or the NNRTI efavirenz in combination with two or three NRTIs. Although the group that received NRTIs only had relatively high rates of virologic suppression at week 48 (61%-74%, depending on the definition of suppression used), rates in the groups that received efavirenz were significantly higher (83%-89%). CD4 increases were similar in all groups, as were serious adverse effects of therapy.

Comment: Thanks in part to these studies (whose results were released some time ago), the NNRTI drugs now are favored for initial antiretroviral treatment. However, these drugs are not without their own problems: Viral resistance to them develops relatively easily, and occasional fatal side effects can occur. At the time of publication, the full text of the first original article was available free of charge.

— Abigail Zuger, MD

Published in Journal Watch General Medicine May 14, 2004

Citation(s):

van Leth F et al. Comparison of first-line antiretroviral therapy with regimens including nevirapine, efavirenz, or both drugs, plus stavudine and lamivudine: A randomised open-label trial, the 2NN study. Lancet 2004 Apr 17; 363:1253-63.

• Medline abstract (Free)

Gulick RM et al. Triple-nucleoside regimens versus efavirenz-containing regimens for the initial treatment of HIV-1 infection. N Engl J Med 2004 Apr 29; 350:1850-61.

• Original article (Subscription may be required)
• Medline abstract (Free)