Document Detail


HIV-1 amino acid changes among participants with virologic failure: associations with first-line efavirenz or atazanavir plus ritonavir and disease status.
MedLine Citation:
PMID:  23148287     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Katie Mollan; Eric S Daar; Paul E Sax; Maya Balamane; Ann C Collier; Margaret A Fischl; Christina M Lalama; Ronald J Bosch; Camlin Tierney; David Katzenstein;
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural     Date:  2012-11-12
Journal Detail:
Title:  The Journal of infectious diseases     Volume:  206     ISSN:  1537-6613     ISO Abbreviation:  J. Infect. Dis.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-11-21     Completed Date:  2013-01-25     Revised Date:  2014-10-02    
Medline Journal Info:
Nlm Unique ID:  0413675     Medline TA:  J Infect Dis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1920-30     Citation Subset:  AIM; IM    
Data Bank Information
Bank Name/Acc. No.:
ClinicalTrials.gov/NCT00118898
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MeSH Terms
Descriptor/Qualifier:
Adult
Amino Acid Substitution
Anti-HIV Agents / pharmacology,  therapeutic use
Benzoxazines / pharmacology*,  therapeutic use
Drug Resistance, Viral*
Female
HIV Infections / drug therapy,  pathology,  virology*
HIV-1 / drug effects,  genetics*,  isolation & purification
Humans
Male
Mutation, Missense*
Oligopeptides / pharmacology*,  therapeutic use
Pyridines / pharmacology*,  therapeutic use
Ritonavir / pharmacology*,  therapeutic use
Treatment Failure
Grant Support
ID/Acronym/Agency:
AI38858/AI/NIAID NIH HHS; AI68634/AI/NIAID NIH HHS; P30 AI060354/AI/NIAID NIH HHS; U01AI068636/AI/NIAID NIH HHS; UL1 RR024160/RR/NCRR NIH HHS; UL1 RR024989/RR/NCRR NIH HHS; UL1 TR000124/TR/NCATS NIH HHS; UM1 AI069477/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Anti-HIV Agents; 0/Benzoxazines; 0/Oligopeptides; 0/Pyridines; JE6H2O27P8/efavirenz; O3J8G9O825/Ritonavir; QZU4H47A3S/atazanavir
Comments/Corrections

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