HIV-1 amino acid changes among participants with virologic failure: associations with first-line efavirenz or atazanavir plus ritonavir and disease status.

TitleHIV-1 amino acid changes among participants with virologic failure: associations with first-line efavirenz or atazanavir plus ritonavir and disease status.
Publication TypeJournal Article
Year of Publication2012
AuthorsMollan K, Daar ES, Sax PE, Balamane M, Collier AC, Fischl MA, Lalama CM, Bosch RJ, Tierney C, Katzenstein D
Corporate AuthorsAIDS Clinical Trials Group Study A5202 Team
JournalJ Infect Dis
Volume206
Issue12
Pagination1920-30
Date Published2012 Dec 15
ISSN1537-6613
KeywordsAdult, Amino Acid Substitution, Anti-HIV Agents, Atazanavir Sulfate, Benzoxazines, Drug Resistance, Viral, Female, HIV Infections, HIV-1, Humans, Male, Mutation, Missense, Oligopeptides, Pyridines, Ritonavir, Treatment Failure
Abstract

BACKGROUND: Although specific human immunodeficiency virus type 1 (HIV-1) drug resistance mutations are well studied, little is known about cumulative amino acid changes, or how regimen and participant characteristics influence these changes.

METHODS: In the AIDS Clinical Trials Group randomized study A5202 of treatment-naive HIV-infected participants, cumulative HIV-1 amino acid changes from pretreatment to virologic failure were evaluated in protease and reverse transcriptase (RT) gene sequences.

RESULTS: Among 265 participants with virologic failure, those assigned atazanavir plus ritonavir (ATV/r) did not have significantly more protease changes compared with those assigned efavirenz (EFV) (P ≥ .13). In contrast, participants with virologic failure assigned EFV had more RT changes, including and excluding known resistance codons (P < .001). At pretreatment, lower CD4 cell count, major resistance, more amino acid mixtures (all P < .001), hepatitis C antibody negativity (P = .05), and black race/ethnicity (P = .02) were associated with more HIV-1 amino acid changes.

CONCLUSIONS: Virologic failure following EFV-containing treatment was associated with more HIV-1 amino acid changes compared to failure of ATV/r-containing treatment. Furthermore, we show that non-drug resistance mutations occurred more frequently among those failing EFV, the clinical relevance of which warrants further investigation. Pretreatment immunologic status may play a role in viral evolution during treatment, as evidenced by increased amino acid changes among those with lower pretreatment CD4 count.

CLINICAL TRIALS REGISTRATION: NCT00118898.

DOI10.1093/infdis/jis613
Alternate JournalJ. Infect. Dis.
PubMed ID23148287
PubMed Central IDPMC3502379
Grant ListAI38858 / AI / NIAID NIH HHS / United States
AI68634 / AI / NIAID NIH HHS / United States
P30 AI060354 / AI / NIAID NIH HHS / United States
U01AI068636 / AI / NIAID NIH HHS / United States
UL1 RR024160 / RR / NCRR NIH HHS / United States
UL1 RR024989 / RR / NCRR NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
UM1 AI069477 / AI / NIAID NIH HHS / United States