title: 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.
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.
authors.affiliation: Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Jessica H
authors.initials: JH
authors.lastname: Brehm
authors.forename: Christina M
authors.initials: CM
authors.lastname: Lalama
authors.forename: Michael D
authors.initials: MD
authors.lastname: Hughes
authors.forename: Richard
authors.initials: R
authors.lastname: Haubrich
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Riddler
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sluis-Cremer
authors.forename: John W
authors.initials: JW
authors.lastname: Mellors
mesh_terms: D000480:Alkynes; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D048588:Benzoxazines / Q000627:therapeutic use*; D003521:Cyclopropanes; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy*; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D020125:Mutation, Missense; D009705:Nucleosides / Q000627:therapeutic use*; D012367:RNA, Viral / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D009705:Nucleosides; D012367:RNA, Viral; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; C098320:efavirenz