Phenotypic drug resistance patterns in subtype A HIV-1 clones with nonnucleoside reverse transcriptase resistance mutations.
We analyzed the nonnucleoside reverse transcriptase (RT) inhibitor (NNRTI) susceptibility of 29 subtype A HIV-1 clones isolated from 10 Ugandan women after single-dose nevirapine (NVP) administration. Six clones had no NNRTI resistance-associated mutations ("wild type"), eight had K103N, nine had Y181C, five had G190A, and one had Y181S. Three clones displayed unexpected phenotypic drug susceptibility/resistance based on their RT genotypes. One wild-type clone had reduced susceptibility to NVP, delavirdine (DLV), and efavirenz (EFV), one clone with K103N was susceptible to all three NNRTIs, and one clone with G190A had extreme hypersusceptibility to DLV. Three unusual HIV-1 RT amino acid substitutions may have contributed to the unexpected phenotypes of the clones: I31T, N136S, and N265D. These polymorphisms were rarely detected among 47,900 HIV-1 genotypes from clinical samples of predominantly United States origin. Further studies are needed to define the genetic correlates of antiretroviral drug resistance in nonsubtype B HIV-1.
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. seshlem@jhmi.edu
Susan H
SH
Eshleman
Dana
D
Jones
Justin
J
Galovich
Ellen E
EE
Paxinos
Christos J
CJ
Petropoulos
J Brooks
JB
Jackson
Neil
N
Parkin
D000480:Alkynes; D019943:Amino Acid Substitution; D019380:Anti-HIV Agents / Q000494:pharmacology*; D048588:Benzoxazines; D002999:Clone Cells; D003521:Cyclopropanes; D020008:Delavirdine / Q000494:pharmacology; D024882:Drug Resistance, Viral; D005260:Female; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000145:classification* / Q000187:drug effects*; D006801:Humans; D009154:Mutation; D019829:Nevirapine / Q000494:pharmacology; D010078:Oxazines / Q000494:pharmacology; D011110:Polymorphism, Genetic; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology*
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D010078:Oxazines; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine; D020008:Delavirdine; D054303:HIV Reverse Transcriptase; C098320:efavirenz