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Metabolic Analyses within A5095: Effect of Efavirenz against an All-nucleoside/Nucleotide Background
Cecilia Shikuma*1, Y Yang2, W Meyer3, M Glesby4, K Tashima5, H Ribaudo2, N Webb6, B Bastow7, D Kuritzkes8, R Gulick4, and AIDS Clin Trials Group A5095 Study Team
1Univ of Hawaii, Honolulu, US; 2Harvard Sch of Publ Hlth, Boston, MA, US; 3Quest Diagnostics, Baltimore, MD, US; 4Cornell Univ, New York, NY, US; 5Brown Univ, Providence, RI, US; 6Frontier Sci & Tech Res Fndn, Amherst, NY, US; 7Social & Sci Systems, Silver Spring, MD, US; and 8Harvard Sch of Publ Hlth, Cambridge, MA, US
Background: Limited prospective data
exist on the metabolic effects of protease inhibitor (PI)-sparing regimens when
used as initial treatment for HIV. We report on fasting metabolic and body
composition changes seen in 1147 treatment-naïve subjects who initiated such
regimens.
Methods: Week-0
to -24 changes in fasting metabolic (triglyceride [TG] and total [T-C], LDL
[LDL-C], and HDL [HDL-C] cholesterol, lactate, glucose, insulin resistance by homeostasis model assessment [HOMA])
and anthropometric indices (waist, hip, and arm circumferences) were compared
in subjects randomized to the 3 arms of ACTG 5095: zidovudine/lamivudine/abacavir
(ZDV/3TC/ABC) vs ZDV/3TC + efavirenz
(EFV) vs ZDV/3TC/ABC + EFV. Changes from weeks 0 to 96
were assessed in the 2 EFV-containing arms. The ZDV/3TC/ABC arm was
discontinued early because of a higher rate of virologic failure, and patients
with HIV RNA <200 copies/mL
were offered randomization to intensify their regimen with either EFV or TDF
(occurred after week 24). Metabolic changes from this new baseline at week 24
to week 96 were compared between the EFV vs TDF arms.
Kruskal-Wallis test was used for comparing
between-group differences in continuous outcomes.
Results: From wk 0-24, median changes (mg/dL; intent-to-treat) in the ZDV/3TC/ABC, ZDV/3TC + EFV and
ZDV/3TC/ABC + EFV arms, respectively, were: TG (–1,7,18); T-C (5, 23, 29); LDL-C (1, 9, 14);
HDL-C (5, 10, 10), lactate (1.3, 1.5, 1.4) and glucose (5, 6, 6), with median
increases in log (HOMA IR) of 0.26, 0.13, 0.19 (p
<0.05 for all except TG and LDL changes in the ZDV/3TC/ABC arm. Similar
values were seen in the as-treated analyses. By intent to treat, T-C, LDL-C,
and HDL-C values were higher in both EFV-containing arms than in the
ZDV/3TC/ABC arm (p <0.001). Anthropometric
changes were not different among arms (p >0.09). No
consistent differences were noted with the addition of ABC to ZDV/3TC/EFV from
week 0 to 24 or from week 0 to 96. Following randomization to EFV vs TDF in the original ZDV/3TC/ABC arm, median changes from
week 24 to 96 in T-C, LDL-C, and HDL-C were higher in the EFV vs TDF arm: T-C (34, –2); LDL-C (23, 5); and HDL-C (4, –2)
(intent to treat, p ≤0.001); TG changes were
similar (32, 17).
Conclusions: Over the course of the
study, minimal to modest changes were seen in all assessed metabolic parameters
except 0- to 24-week TG and LDL changes in the ZDV/3TC/ABC arm. Compared to all
nucleoside/nucleotide-based regimens, the inclusion of EFV 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.
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