Triple-nucleoside regimen inferior to efavirenz-containing regimen for HIV therapy

NEW YORK (Reuters Health) - In a diverse group of previously untreated HIV-1-infected patients, the triple-nucleoside combination of abacavir, zidovudine, and lamivudine proved to be "virologically inferior" to a regimen containing the nonnucleoside inhibitor efavirenz plus two or three nucleoside analogues.

That’s according to a large, randomized double-blind trial reported in the April 29th issue of The New England Journal of Medicine by Dr. Roy M. Gulick of the Cornell Clinical Trials Unit in New York and a multicenter team of U.S.-based colleagues.

"Our findings suggest that an efavirenz-containing regimen is more potent than the triple-nucleoside regimen and support current guidelines that recommend efavirenz-based regimens among the preferred options for the initial treatment of HIV-1 infection," they write.

In the trial, 1147 subjects with a mean baseline HIV-1 RNA level of 4.85 log10 copies/mL and mean CD4 counts of 238 cells per cubic millimeter were randomly assigned to one of three arms: abacavir-zidovudine-lamivudine; zidovudine-lamivudine plus efavirenz; or zidovudine-lamivudine-abacavir plus efavirenz.

A "scheduled review" by the data and safety monitoring board led to the recommendation to halt the triple-nucleoside arm and present the results in that arm in comparison to pooled data from the efavirenz groups, the investigators report.

Data analysis showed that after a median of 32 weeks, significantly more patients in the triple-nucleoside arm had virologic failure than in the combined efavirenz groups (21% vs 11%). They also report that the time to virologic failure was significantly shorter in the triple-nucleoside arm (p < 0.001).

These differences were observed "regardless of the pretreatment viral load or the CD4-cell-count stratum."

There were no significant differences between the groups in CD4 count changes or in the incidence of grade 3 or 4 adverse events.

Protease-sparing triple-nucleoside regimens are simple to take and widely used as initial therapy for HIV-infection, Dr. Gulick and colleagues note. However, few studies have directly compared these regimens to currently recommended regimens.

"Clinicians," the investigators write, "should factor in the results of appropriately designed, comparative studies such as ours in selecting the optimal initial antiretroviral regimen with an individual patient."

N Engl J Med 2004;350:1850-1861.