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Effect of Baseline Characteristics on Treatment Outcomes in ACTG 5142: A Prospective, Randomized, Phase III Trial of NRTI-, PI-, and NNRTI-sparing Regimens for Initial Treatment of HIV-1 Infection
Sharon Riddler*1, R Haubrich2, G DiRienzo3, L Peeples3, W Powderly4, K Garren5, D Butcher6, J Rooney7, D Havlir8, J Mellors1, and AIDS Clinical Trials Group 5142 Study Team
1Univ of Pittsburgh, PA, US; 2Univ of California, San Diego, US; 3Harvard Sch of Publ Hlth, Boston, MA, US; 4Univ Coll Dublin, Ireland; 5Abbott Labs, Abbott Park, IL, US; 6Bristol-Myers Squibb, Plainsboro, NJ, US; 7Gilead Sci, Foster City CA, US; and 8Univ of California, San Francisco, US
Background: Current guidelines recommend efavirenz (EFV)
or boosted protease inhibitor (PI) -based regimens as initial therapy for all
patients. The effect of baseline factors on the outcome of treatment was
evaluated in subjects receiving 3 potent class-sparing regimens.
Methods: A5142 randomized 753 treatment-naļve
subjects (20% women) to class-sparing regimens: EFV+2 NRTI vs lopinavir (LPV) +2NRTI
vs LPV+EFV (LPV/EFV). NRTI were lamivudine (3TC) + zidovudine (ZDV), stavudine
extended-release formulation (d4T XR), or tenofovir (TDF). Associations of baseline
characteristics with risk of virologic failure, time-to-treatment limiting
toxicity (any regimen component), and CD4 change were analyzed using Cox
proportional hazards models. Analyses were intent-to-treat.
Results: A shorter time to virologic failure was
associated with younger age, female sex, lower baseline CD4, and black race.
Sex differences between regimens were observed. For women, the risk of virologic
failure was lowest for LPV/EFV and the time-to-treatment limiting toxicity was
shorter for NRTI-containing regimens vs LPV/EFV.
*Multivariate HR stratified on screening HIV RNA, hepatitis,
NRTI;
number <1 signifies less risk;
**<100, 100-199, 200-299, 300-500, >500.
Overall, baseline virologic failure (<100,000 vs
≥100,000) was not associated with the risk of virologic failure (log rank
p = 0.81). Although both LPV regimens had greater CD4 cell increases at
week 96, the time to CD4 >200 cells/mm3 for subjects with initial
CD4 <50 cells/mm3 (n = 177) was not different for the 3
treatment groups (log rank p = 0.77; median time to CD4>200 cells/mm3
was 55 weeks).
Conclusions: In this large randomized trial of class-sparing
regimens, virologic failure was more likely with lower baseline CD4 cell count,
black race, younger age, and female sex; however, women had a longer time to virologic
failure and less toxicity with the nucleoside sparing regimen of LPV/EFV,
suggesting greater nucleoside toxicity for women than men. All regimens were
similar in the time required to reach CD4 cell count above the clinically
significant threshold of 200 cells/mm3.
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