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

TitleInitial 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
Publication TypeJournal Article
Year of Publication2011
AuthorsHaubrich RH, Riddler SA, Ribaudo H, Direnzo G, Klingman KL, Garren KW, Butcher DL, Rooney JF, Havlir DV, Mellors JW
Corporate AuthorsAIDS Clinical Trials Group(ACTG) A5160 and A5142 Study Teams
JournalAIDS
Volume25
Issue18
Pagination2269-78
Date Published2011 Nov 28
ISSN1473-5571
KeywordsAdult, Benzoxazines, Drug Therapy, Combination, Female, Follow-Up Studies, HIV Infections, HIV Protease Inhibitors, HIV-1, Humans, Lopinavir, Male, Middle Aged, Reverse Transcriptase Inhibitors, Ritonavir, RNA, Viral, Sex Factors, Treatment Outcome, Viral Load
Abstract

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 log(10)  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 log(10)  copies/ml) than either the LPV/EFV or LPV groups (-1.21 and -1.16 log(10 ) 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.

DOI10.1097/QAD.0b013e32834d0c20
Alternate JournalAIDS
PubMed ID21941167
PubMed Central IDPMC3572727
Grant ListAI 060354 / AI / NIAID NIH HHS / United States
AI 064086 / AI / NIAID NIH HHS / United States
AI 068634 / AI / NIAID NIH HHS / United States
AI 069411 / AI / NIAID NIH HHS / United States
AI 069418 / AI / NIAID NIH HHS / United States
AI 069419 / AI / NIAID NIH HHS / United States
AI 069423 / AI / NIAID NIH HHS / United States
AI 069424 / AI / NIAID NIH HHS / United States
AI 069432 / AI / NIAID NIH HHS / United States
AI 069434 / AI / NIAID NIH HHS / United States
AI 069439 / AI / NIAID NIH HHS / United States
AI 069447 / AI / NIAID NIH HHS / United States
AI 069450 / AI / NIAID NIH HHS / United States
AI 069452 / AI / NIAID NIH HHS / United States
AI 069465 / AI / NIAID NIH HHS / United States
AI 069470 / AI / NIAID NIH HHS / United States
AI 069471 / AI / NIAID NIH HHS / United States
AI 069472 / AI / NIAID NIH HHS / United States
AI 069474 / AI / NIAID NIH HHS / United States
AI 069477 / AI / NIAID NIH HHS / United States
AI 069484 / AI / NIAID NIH HHS / United States
AI 069494 / AI / NIAID NIH HHS / United States
AI 069495 / AI / NIAID NIH HHS / United States
AI 069501 / AI / NIAID NIH HHS / United States
AI 069502 / AI / NIAID NIH HHS / United States
AI 069532 / AI / NIAID NIH HHS / United States
AI 069556 / AI / NIAID NIH HHS / United States
AI 25859 / AI / NIAID NIH HHS / United States
AI 27661 / AI / NIAID NIH HHS / United States
AI 27673 / AI / NIAID NIH HHS / United States
AI 32782 / AI / NIAID NIH HHS / United States
AI 32783 / AI / NIAID NIH HHS / United States
AI 34853 / AI / NIAID NIH HHS / United States
AI 36214 / AI / NIAID NIH HHS / United States
AI 38858 / AI / NIAID NIH HHS / United States
AI 45008 / AI / NIAID NIH HHS / United States
AI 46370 / AI / NIAID NIH HHS / United States
AI 46376 / AI / NIAID NIH HHS / United States
AI 46381 / AI / NIAID NIH HHS / United States
AI 50410 / AI / NIAID NIH HHS / United States
AI06951 / AI / NIAID NIH HHS / United States
DA 12121 / DA / NIDA NIH HHS / United States
K24 AI051982 / AI / NIAID NIH HHS / United States
K24 AI064086 / AI / NIAID NIH HHS / United States
K24 AI064086-06 / AI / NIAID NIH HHS / United States
P30 AI027763 / AI / NIAID NIH HHS / United States
P30 AI050410 / AI / NIAID NIH HHS / United States
RR 00032 / RR / NCRR NIH HHS / United States
RR 00039 / RR / NCRR NIH HHS / United States
RR 00044 / RR / NCRR NIH HHS / United States
RR 00046 / RR / NCRR NIH HHS / United States
RR 00047 / RR / NCRR NIH HHS / United States
RR 00051 / RR / NCRR NIH HHS / United States
RR 00052 / RR / NCRR NIH HHS / United States
RR 00075 / RR / NCRR NIH HHS / United States
RR 00096 / RR / NCRR NIH HHS / United States
RR 02635 / RR / NCRR NIH HHS / United States
U01 AI069423 / AI / NIAID NIH HHS / United States
UL1 RR024989 / RR / NCRR NIH HHS / United States
UL1 RR025008 / RR / NCRR NIH HHS / United States
UL1 TR000454 / TR / NCATS NIH HHS / United States