Initial Viral Decay to Assess the Relative Antiretroviral Potency of PI-, NNRTI-, and NRTI-Sparing Regimens for First Line Therapy of HIV-1 Infection: ACTG 5160s (sub-study of A5142)
Richard H. Haubrich*1, S Riddler2, H Ribaudo3, G DiRienzo3, K Klingman4, K Garren5, T George6, J Rooney7, D Havlir8, J Mellors2, and the AIDS Clinical Trials Group 5160s Study Team
1Univ of California, San Diego, US; 2Univ of Pittsburgh, PA, US; 3Harvard Sch of Publ Hlth, Statistical and Data Analysis Ctr, Boston, MA, US; 4Div of AIDS, NIAID, NIH, Bethesda, MD, US; 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
viral clearance (phase-1 decay half-life [PH1]) has been useful to compare
regimen potency. The objectives of this study were to compare PH1 of 3 regimens
to evaluate gender differences and to relate PH1 to longer-term virologic responses:
lopinavir/ritonavir + efavirenz
(L/E) vs lopinavir/ritonavir
+ 2 nucleoside reverse transcriptase inhibitor (NRTI) (LPV)
vs efavirenz + 2 NRTI (EFV).
Methods: Sub-study of randomized,
open-label 96-week trial. HIV RNA (viral load) measured at days 2, 10, and 14
in A5160s and days 7, 28, and 56 in A5142. For A5160s, PH1 was estimated with
bi-exponential mixed-effects modeling using on-treatment data and compared
using Wilcoxon tests. Viral load change to day 7 (VIRAL
LOAD C7) was analyzed using linear models and associated with viral load <200
at weeks 24 and 48 (controlling for baseline viral load) using logistic
regression for eligible A5142 patients (n
= 575); p-values were not
corrected for multiple comparisons.
Results: We enrolled 68 subjects in
A5160s (50% female, 53% non-white, median CD4 183, median viral load 4.9). In
A5160s, PH1 was significantly shorter for EFV than LPV (1.1 vs
1.3 days, p = 0.03); other
between-arm comparisons were not significant (p >0.1). Overall, PH1 was not different by gender (p = 0.14); however, within the LPV arm,
women had slower clearance than men (1.7 vs 1.1 days,
p = 0.03). In A5142, VLC7 was greater
for EFV (–1.49, 95%CI 1.42, 1.57) than both L/E and LPV (–1.23, 95%CI 1.16, 1.31
and –1.17, 95%CI 1.10, 1.26; p <0.001).
VLC7 was also greater for patients with baseline viral load >100,000 vs <100,000 (–1.62, 95%CI 1.54, 1.70 vs
–1.16, 95%CI 1.10, 1.21; p <0.001).
Gender, race/ethnicity, and interaction terms were not significant (p >0.15). VLC7 was significantly associated
with week 48 viral load <200 (p = 0.01),
but not week 24 (p = 0.12).
Conclusions: Early viral
clearance, as evaluated by phase-1 viral load decay and day 7 viral load change, was
greater for EFV than LPV or L/E. Phase-1 decay was not different for subjects
by gender and race/ethnicity. Day 7 viral load change predicted week-48