September 15, 2006 (Reuters Health)—HIV outcomes may vary with differing initial highly active antiretroviral therapy (HAART) regimens, according to a report in the September 1st issue of The Journal of Infectious Diseases.

Although various comparative trials of antiretroviral regimens have been reported, the authors explain, no trials have compared the clinical efficacy of the most commonly prescribed regimens.

The Antiretroviral Therapy Cohort Collaboration (ART-CC) evaluated progression to death from any cause and to AIDS or death associated with various third drugs and with a variety of nucleoside reverse-transcriptase inhibitor (NRTI) pairs.

There was little difference among third drugs and NRTI pairs in the progression to AIDS/death, the authors report.

In contrast, the results indicate, patients receiving efavirenz as a third drug appeared to fare best when mortality was considered, as did patients receiving the NRTI combination zidovudine/lamivudine (AZT/3TC).

Similarly, researchers say, patients starting with efavirenz and patients receiving AZT/3TC were more likely than others to suppress HIV-1 RNA level by the 6-month time point.

Efavirenz in combination with AZT/3TC was more effective in suppressing HIV-1 RNA levels than efavirenz in combination with stavudine/didanosine (D4T/DDI), the report indicates, but NRTI pairs in combination with nelfinavir showed no such difference.

"In our analysis, efavirenz appears to be more efficacious than any other third drug in a HAART regimen," the investigators write. "These differences could be attributed to the superiority of efavirenz or might reflect underlying unmeasured differences in the ways in which physicians prescribe and patients use efavirenz, compared with other third drugs."

"Relevant differences in long-term outcomes may exist and large trials are needed," corresponding author Dr. Mattias Egger from University of Bern, Switzerland told Reuters Health.

Based on the findings of this report, Dr. Egger said that efavirenz would be a good choice as the third drug in an initial HAART regimen, depending, of course, on the specific clinical situation.

"The results are reassuring, because they support recommendations given in international treatment guidelines that efavirenz-based HAART be considered a preferred regimen for the initial treatment of HIV infection," writes Dr. Michael D. Hughes from Harvard University, Boston, in a related editorial.

"Although it is unrealistic to expect all trials of initial treatment to be powered to evaluate clinical end points," Dr. Hughes concludes, "a policy requiring follow-up of all randomized patients for long-term vital status (and, wherever possible, for significant disease and drug-related morbidity) would facilitate cross-trial analyses that might help to address important questions about treatment management and, by building on the randomization, to reduce the potential for confounding by unmeasured factors that is inherent in cohort studies."

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