Failure of initial therapy with two nucleosides and efavirenz is not associated with early emergence of mutations in the C-terminus of HIV-1 reverse transcriptase.

TitleFailure of initial therapy with two nucleosides and efavirenz is not associated with early emergence of mutations in the C-terminus of HIV-1 reverse transcriptase.
Publication TypeJournal Article
Year of Publication2011
AuthorsBrehm JH, Lalama CM, Hughes MD, Haubrich R, Riddler SA, Sluis-Cremer N, Mellors JW
Corporate AuthorsAIDS Clinical Trials Group Study A5142 Protocol Team
JournalJ Acquir Immune Defic Syndr
Volume56
Issue4
Pagination344-8
Date Published2011 Apr
ISSN1944-7884
KeywordsAnti-HIV Agents, Antiretroviral Therapy, Highly Active, Benzoxazines, Drug Resistance, Viral, HIV Infections, HIV Reverse Transcriptase, HIV-1, Humans, Mutation, Missense, Nucleosides, RNA, Viral, Sequence Analysis, DNA
Abstract

It is uncertain how often mutations in the connection or RNase H domains of HIV-1 reverse transcriptase (RT) emerge with failure of first-line antiretroviral therapy. Full-length RT sequences in plasma obtained pretherapy and at virologic failure were compared in 53 patients on first-line efavirenz-containing regimens from AIDS Clinical Trials Group study A5142. HIV-1 was mostly subtype B (48 of 53). Mutations in the polymerase but not in connection or RNase H domains of RT increased in frequency between pretherapy and failure (K103N, P = 0.001; M184I/V, P = 0.016). Selection of mutations in C-terminal domains of RT is not common with early failure of efavirenz-containing regimens.

DOI10.1097/QAI.0b013e31820cf029
Alternate JournalJ. Acquir. Immune Defic. Syndr.
PubMed ID21350368
PubMed Central IDPMC3086845
Grant List5T32AI065380-04 / AI / NIAID NIH HHS / United States
AI064086 / AI / NIAID NIH HHS / United States
AI27670 / AI / NIAID NIH HHS / United States
AI36214 / AI / NIAID NIH HHS / United States
AI69432 / AI / NIAID NIH HHS / United States
K24 AI064086 / AI / NIAID NIH HHS / United States
K24 AI064086-06 / AI / NIAID NIH HHS / United States
P30 AI036214 / AI / NIAID NIH HHS / United States
P30 AI036214-10 / AI / NIAID NIH HHS / United States
R01 AI081571 / AI / NIAID NIH HHS / United States
R01 AI081571-03 / AI / NIAID NIH HHS / United States
R01AI081571 / AI / NIAID NIH HHS / United States
T32 AI065380 / AI / NIAID NIH HHS / United States
T32 AI065380-04 / AI / NIAID NIH HHS / United States
T32-5TL1RR024155-04 / RR / NCRR NIH HHS / United States
TL1 RR024155 / RR / NCRR NIH HHS / United States
TL1 RR024155-04 / RR / NCRR NIH HHS / United States
TL1 TR000145 / TR / NCATS NIH HHS / United States
U01 AI027670 / AI / NIAID NIH HHS / United States
U01 AI027670-18S1 / AI / NIAID NIH HHS / United States
U01 AI038858 / AI / NIAID NIH HHS / United States
U01 AI038858-04 / AI / NIAID NIH HHS / United States
U01 AI069432 / AI / NIAID NIH HHS / United States
U01 AI069432-01 / AI / NIAID NIH HHS / United States
U01AI38858 / AI / NIAID NIH HHS / United States
UL1 TR000454 / TR / NCATS NIH HHS / United States