Detection of drug-resistant minority variants of HIV-1 during virologic failure of indinavir, lamivudine, and zidovudine.
We evaluated zidovudine-experienced patients for whom treatment with indinavir, lamivudine, and zidovudine failed, for indinavir-resistant minority variants. Of 10 patients with plasma human immunodeficiency virus type 1 RNA suppression and subsequent rebound, 6 without primary indinavir-resistance mutations underwent clonal analysis. One had evidence of V82A in 9 of 30 clones at week 24, with no increase at week 40. The dominant week-40 82V-M184V clones had changes at protease codons 62-64, compared with all clones at week 24 and minority clones at week 40. Resistance to indinavir can emerge during treatment failure in nucleoside-experienced patients but may be missed by routine sequence analysis. Selection for indinavir-resistant variants on treatment with indinavir, lamivudine, and zidovudine may occur slowly, depending on the genetic context in which they arise.
University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA.
Carrie
C
Dykes
Joe
J
Najjar
Ronald J
RJ
Bosch
Michael
M
Wantman
Manohar
M
Furtado
Stephen
S
Hart
Scott M
SM
Hammer
Lisa M
LM
Demeter
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy* / Q000276:immunology / Q000821:virology; D018791:CD4 Lymphocyte Count; D024882:Drug Resistance, Viral; D016333:HIV Protease / Q000235:genetics; D054303:HIV Reverse Transcriptase / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D019469:Indinavir / Q000627:therapeutic use*; D019259:Lamivudine / Q000627:therapeutic use*; D009154:Mutation; D012367:RNA, Viral / Q000097:blood; D015215:Zidovudine / Q000627:therapeutic use*
D012367:RNA, Viral; D019259:Lamivudine; D015215:Zidovudine; D019469:Indinavir; D054303:HIV Reverse Transcriptase; D016333:HIV Protease