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.
Dykes
Carrie
C
University of Rochester School of Medicine and Dentistry, Rochester, New York 14642, USA.
Najjar
Joe
J
Bosch
Ronald J
RJ
Wantman
Michael
M
Furtado
Manohar
M
Hart
Stephen
S
Hammer
Scott M
SM
Demeter
Lisa M
LM
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