Emerging integrase inhibitor resistance mutations in raltegravir-treated HIV-1-infected patients with low-level viremia.

TitleEmerging integrase inhibitor resistance mutations in raltegravir-treated HIV-1-infected patients with low-level viremia.
Publication TypeJournal Article
Year of Publication2011
AuthorsGallien S, Delaugerre C, Charreau I, Braun J, Boulet T, Barrail-Tran A, de Castro N, Molina J-M, Kuritzkes DR
JournalAIDS
Volume25
Issue5
Pagination665-9
Date Published2011 Mar 13
ISSN1473-5571
KeywordsAdult, CD4 Lymphocyte Count, Drug Resistance, Viral, Female, HIV Infections, HIV Integrase, HIV Integrase Inhibitors, HIV-1, Humans, Male, Mutation, Pyrrolidinones, Raltegravir Potassium, Viremia
Abstract

BACKGROUND: The emergence of integrase strand-transfer inhibitor (INSTI) resistance-associated mutations was examined in patients with low-level viremia after switching from enfuvirtide to raltegravir in the ANRS 138-Easier trial.

METHODS: Integrase genes of plasma virus from raltegravir-treated patients in the Easier trial with low-level viremia (50-500 copies/ml) were sequenced to determine INSTI resistance-associated mutations. Baseline viral load, baseline and nadir CD4 cell count, antiretroviral treatment, genotypic susceptibility score, level of viremia and degree of treatment adherence during the study period were also analyzed.

RESULTS: Forty-nine patients experienced at least one episode of low-level viremia while receiving raltegravir; integrase genotyping was successful in samples from 39 individuals (80%). Among them, three [7.7%, 95% confidence interval (CI) 1.6-20.9%] had significant INSTI resistance mutations consisting of N155H in two and P145S in one. Absence of these mutations from proviral DNA at baseline suggested selection of INSTI resistance during episodes of low-level viremia. No specific factors significantly associated with emergence of INSTI resistance mutations during low-level viremia were identified.

CONCLUSION: Emergence of INSTI resistance mutations can occur during episodes of low-level viremia in patients receiving raltegravir-containing regimens.

DOI10.1097/QAD.0b013e3283445834
Alternate JournalAIDS
PubMed ID21326075
PubMed Central IDPMC3265637
Grant ListAI068636 / AI / NIAID NIH HHS / United States
K24 RR016482 / RR / NCRR NIH HHS / United States
K24 RR016482 / RR / NCRR NIH HHS / United States
K24 RR016482-10 / RR / NCRR NIH HHS / United States
U01 AI068636-05 / AI / NIAID NIH HHS / United States