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Initial viral decay to assess the relative antiretroviral potency of protease inhibitor-sparing, nonnucleoside reverse transcriptase inhibitor-sparing, and nucleoside reverse transcriptase inhibitor-sparing regimens for first-line therapy of HIV infection

Haubrich, Richard H.a; Riddler, Sharon A.b; Ribaudo, Heatherc; DiRenzo, Gregoryc,d; Klingman, Karin L.e; Garren, Kevin W.f; Butcher, David L.g; Rooney, James F.h; Havlir, Diane V.i; Mellors, John W.b; for the AIDS Clinical Trials Group (ACTG) A5160 and A5142 Study Teams

doi: 10.1097/QAD.0b013e32834d0c20
Clinical Science

Objectives: To evaluate the effects of sex and initial antiretroviral regimen on decay of HIV-RNA and virologic outcome.

Methods: We conducted a viral dynamics substudy of A5142, a trial comparing lopinavir (LPV)/ritonavir with efavirenz (LPV/EFV) versus LPV and two nucleoside reverse transcriptase inhibitor (NRTI) (LPV) versus EFV and two NRTI (EFV) in antiretroviral (ARV)-naive individuals. HIV-RNA was measured at days 2, 10, and 14 in the substudy and at weeks 1, 4, and 8 in A5142 participants. Two-phase viral decay was estimated in the substudy with biexponential mixed-effects modeling and compared using Wilcoxon tests. Week 1 HIV-RNA change was assessed as a predictor of virologic failure (HIV-RNA above 50 or 200 copies/ml) at weeks 24–96 using logistic regression.

Results: Sixty-eight individuals were enrolled in the substudy (median HIV-RNA 4.9 log10 copies/ml). Median rates of phase 1 viral decay by treatment were 0.61(EFV/LPV), 0.53(LPV), and 0.63(EFV) per day. Phase 1 decay was significantly faster for EFV than LPV (P = 0.023); other comparisons were not significant (P > 0.11). Viral decay did not differ by sex (P = 0.10). Week 1 HIV-RNA change, calculated in 571 participants of A5142, was greater for the EFV (median −1.47 log10 copies/ml) than either the LPV/EFV or LPV groups (−1.21 and −1.16 log10 copies/ml, respectively; P < 0.001). Week 1 HIV-RNA change was associated with virologic failure above 50 copies/ ml at weeks 24 and 48 (P< 0.018), but not above 200 copies/ml at these time points or for any value at week 96.

Conclusion: Phase 1 decay was faster for EFV than LPV or LPV/EFV. Week 1 HIV-RNA change predicted virologic outcome up to week 48, but not at week 96.

aAntiviral Research Center, University of California San Diego, San Diego, California

bUniversity of Pittsburgh, Pittsburgh, Pennsylvania

cStatistical and Data Analysis Center, Harvard School of Public Health, Boston, Massachusetts

dState University of New York at Albany, Albany, New York

eDivision of AIDS, National Institute of Allergy and Infectious Diseases (NIAID), Bethesda, Maryland

fAbbott Laboratories, Abbott Park, Illinois

gVirology Medical Affairs, Bristol-Myers Squibb, Plainsboro, New Jersey

hGilead Sciences, Foster City

iUniversity of California San Francisco, San Francisco, California, USA.

Correspondence to Richard H. Haubrich, MD, Antiviral Research Center, University of California, San Diego, 200 West Arbor Drive, Mail Code 8208, San Diego, CA 92103, USA. Tel: +1 619 543 8080; fax: +1 619 543 5066; e-mail: rhaubrich@ucsd.edu

Received 2 February, 2011

Revised 28 August, 2011

Accepted 2 September, 2011

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© 2011 Lippincott Williams & Wilkins, Inc.