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NRTIs Have Varying Effects on Serum Lipids and Body Fat: Presented at CROI

By Norra MacReady

LOS ANGELES, CA -- February 27, 2007 -- Drug cocktails with nucleoside reverse transcriptase inhibitors (NRTIs) increase the risk of lipoatrophy to a greater extent than NRTI-free regimens, according to research presented here at the 14^th Conference on Retroviruses and Opportunistic Infections (CROI).

However, NRTIs also are associated with lower serum lipid levels than the NRTI-sparing combination of lopinavir and efavirenz, said Richard Haubrich, MD, professor of medicine, University of California, San Diego, California, United States.

Dr. Haubrich reported the findings from ACTG-5142 -- a prospective, randomised, open-label, phase 3 trial sponsored by the AIDS Clinical Trial Group -- in an oral presentation on February 26^th.

A total of 753 patients were randomised to 1 of 3 arms. Patients in the NRTI-sparing arm were treated with lopinavir and efavirenz. Treatment in the other 2 arms consisted of lopinavir or efavirenz and lamiduvine plus one other NRTI (zidovudine, staduvine, or tenofovir).

Body composition was measured with dual-energy x-ray absorptiometry at baseline, 48 weeks, and 96 weeks. Fasting lipids were studied at 0, 12, 24, 48, 72, and 96 weeks. Among patients taking NRTIs, 42% received zidovudine, 34% received tenofovir, and 24% received staduvine. Lipoatrophy was defined as a loss of 20% or more of body fat.

At baseline, patients were well matched across the 3 study arms, Dr. Haubrich said.

By week 96, among patients in the NRTI-sparing regimen, extremity fat had increased by a median of 18%, corresponding to about 1 kg of body weight. Patients in the lopinavir/ NRTI arm experienced a median 10% increase (0.7 kg). In the efavirenz/ NRTI group, extremity fat showed a median increase of 1.4% (0.05 kg). All of these differences were statistically significant among the different groups.

Trunk fat increased by 12% to 16%, with no significant differences across groups.

Also at 96 weeks, lipoatrophy was observed in 32% of patients receiving efavirenz/ NRTI, 17% of those receiving lopinavir/ NRTI, and 9% of those in the NRTI-sparing group. All of these differences were statistically significant. Among patients in the NRTI arms, lipoatrophy was most common in those receiving stavudine, followed by zidovudine and tenofovir.

As for serum lipids, by 96 weeks, total cholesterol had increased by a median of 57 mg/dL among patients in the NRTI-free group, compared to 33 mg/dL and 32 mg/dL in the efavirenz and lopinavir groups, respectively. The differences between the NRTI-sparing regimen and the other 2 groups were statistically significant. The NRTI-sparing regimen was also associated with the highest increase in serum triglycerides, as well as high-density lipoprotein (HDL) and non-HDL cholesterol.

These findings suggest that NRTI-sparing regimens can minimise lipoatrophy, Dr. Haubrich said. If a patient must take an NRTI, lipoatrophy risk is lowest with tenofovir.

In general, when choosing among recommended regimens containing lopinavir or efavirenz, physicians should weigh the drugs' effects on many factors, including serum lipids as well as body fat distribution.


[Presentation title: Metabolic Outcomes of ACTG 5142: A Prospective, Randomized, Phase III Trial of NRTI-, PI- and NNRTI-Sparing Regimens for Initial Treatment of HIV-1 Infection. Abstract 38]

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