Metabolic and Morphologic Changes with PI-sparing Therapies

By Brian Boyle, MD

There are limited prospective data regarding the metabolic effects of protease inhibitor (PI)-sparing regimens when used as initial ARV treatment. In a report from the ACTG 5095 study, which enrolled 1147 ARV-naďve patients who were randomized to one of 3 PI-sparing regimens: Trizivir® (co-formulated abacavir [ABC]/zidovudine [ZDV]/lamivudine [3TC] vs. Efavirenz (Sustiva®, EFV) + Combivir® (co-formulated zidovudine [ZDV]/lamivudine [3TC]) vs. EFV + Trizivir®, the fasting metabolic and body composition changes were evaluated. 

The week 24 metabolic data and anthropometric indices were available for all 3 arms. Since, the Trizivir® only arm was stopped early due to virologic underperformance and patients randomized to add tenofovir (TDF; Viread) or EFV, these patients were evaluated from a new baseline at week 24 and compared to week 96 data.

The median changes in metabolic values in mg/dl (ITT) from week 0-24 are shown in the Table.

Table

All values are significant (p<0.05) except the triglyceride and LDL-C changes in the Trizivir® only arm and similar values were seen in the as-treated analyses. By ITT analysis, total cholesterol, LDL-C, and HDL-C values were higher in both EFV-containing arms than in the Trizivir® only arm (p<0.001). There was no significant difference, however, in the anthropometric changes between the 3 arms. Following randomization to add EFV or TDF to the original Trizivir® arm, from weeks 24 to 96 the median TG changes (32, 17) were similar but changes were higher in the EFV arm than the TDF regarding total cholesterol (34,-2) , LDL-C (23,5) and HDL-C  (4,-2) (p < 0.001).

The authors conclude, "Over the course of the study, minimal to modest changes were seen in all assessed metabolic parameters except 0-24 week TG and LDL changes in the [Trizivir®] arm. Compared to all nucleoside/nucleotide-based regimens, the inclusion of efavirenz was associated with higher LDL-C as well as higher HDL-C levels. No consistent metabolic effect was noted with the addition of ABC to ZDV/3TC/EFV.”

02/07/06

Reference
C Shikuma et al. Metabolic Analyses within A5095: Effect of Efavirenz against an All-Nucleoside/Nucleotide Background. 13^th Conference on Retroviruses and Opportunistic Infections. Denver, CO. February 5-8, 2006. Abstract 746.