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Differential effects of efavirenz, lopinavir/r, and atazanavir/r on the initial viral decay rate in treatment naïve HIV-1-infected patients.

Journal article
Authors Arvid Edén
Lars-Magnus Andersson
Orjan Andersson
Leo Flamholc
Filip Josephson
Staffan Nilsson
Vidar Ormaasen
Veronica Svedhem
Christer Säll
Anders Sönnerborg
Petra Tunbäck
Magnus Gisslén
Published in AIDS research and human retroviruses
Volume 26
Issue 5
Pages 533-40
ISSN 1931-8405
Publication year 2010
Published at Institute of Clinical Sciences, Department of Dermatology and Venereology
Department of Mathematical Sciences, Mathematical Statistics
Institute of Biomedicine, Department of Infectious Medicine
Pages 533-40
Language en
Links dx.doi.org/10.1089/aid.2009.0177
Keywords Adult, Aged, Anti-HIV Agents, pharmacology, therapeutic use, Benzoxazines, pharmacology, therapeutic use, Drug Therapy, Combination, Female, HIV Infections, drug therapy, virology, HIV-1, drug effects, Humans, Male, Middle Aged, Oligopeptides, pharmacology, therapeutic use, Pyridines, pharmacology, therapeutic use, Pyrimidinones, pharmacology, therapeutic use, RNA, Viral, blood, drug effects, Reverse Transcriptase Inhibitors, pharmacology, therapeutic use, Treatment Outcome
Subject categories Clinical virology, Infectious Medicine

Abstract

Initial viral decay rate may be useful when comparing the relative potency of antiretroviral regimens. Two hundred twenty-seven ART-naïve patients were randomized to receive efavirenz (EFV) (n = 74), lopinavir/ritonavir (LPV/r) (n = 77), or atazanavir/ritonavir (ATV/r) (n = 79) in combination with two NRTIs. The most frequently used NRTI combinations in the EFV and ATV/r groups were the nonthymidine analogues tenofovir and emtricitabine or lamivudine (70% and 68%, respectively) and, in the LPV/r group, lamivudine and the thymidine analogue zidovudine (89%). HIV-1 RNA was monitored during the first 28 days after treatment initiation. Phase 1 and 2 decay rate was estimated in a subset of 157 patients by RNA decrease from days 0 to 7, and days 14 to 28. One-way ANOVA and subsequent Tukey's post hoc tests were used for groupwise comparisons. Mean (95% CI) HIV-1 RNA reductions from days 0 to 28 were 2.59 (2.45-2.73), 2.42 (2.27-2.57), and 2.13 (2.01-2.25) log(10) copies/ml for the EFV-, LPV/r-, and ATV/r-based treatment groups, respectively, with a significantly larger decrease in the EFV-based group at all time points compared with ATV/r (p < 0.0001), and with LPV/r at days 7-21 (p < 0.0001-0.03). LPV/r gave a greater RNA decrease compared with ATV/r from day 14 (p = 0.02). Phase 1 decay rate was significantly higher in the EFV group compared with LPV/r (p = 0.003) or ATV/r (p < 0.0001). No difference was found in phase 2 decrease. EFV-based treatment gave a more rapid decline in HIV-1 RNA than did either of the boosted protease inhibitor-based regimens. The observed differences may reflect different inherent regimen potencies.

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