High levels of drug-resistant human immunodeficiency virus variants in patients exhibiting increasing CD4+ T cell counts despite virologic failure of protease inhibitor-containing antiretroviral combination therapy.
The genotypic mutations associated with indinavir resistance were analyzed in 27 patients who exhibited sustained CD4+ T cell responses to highly active antiretroviral therapy (HAART), despite virologic failure of treatment. After 12 months of HAART, 1 or 2 primary resistance mutations had occurred in 18 (66%) of the patients, and secondary mutations had accumulated in 22 (88%) of the patients. The number and patterns of mutations in the patients who exhibited discrepant responses to HAART did not differ from those observed in patients who exhibited immunologic and virologic failure to therapy. Results indicate that many patients have prolonged immunologic benefits, despite the development of virologic failure and protease inhibitor mutations. The clinical course of this group of patients calls into question the relevance of genotypic resistance and plasma human immunodeficiency virus RNA level as surrogate markers in patients receiving HAART.
Bélec
L
L
Laboratoire de virologie, Hôpital Broussais, 75 674 Paris Cedex 14, France. laurent.belec@brs.ap-hop-paris.fr.
Piketty
C
C
Si-Mohamed
A
A
Goujon
C
C
Hallouin
M C
MC
Cotigny
S
S
Weiss
L
L
Kazatchkine
M D
MD
D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D004352:Drug Resistance, Microbial; D004359:Drug Therapy, Combination; D015684:Gene Products, pol / Q000737:chemistry / Q000235:genetics*; D015751:Genes, pol; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D009154:Mutation; D012367:RNA, Viral / Q000097:blood; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D017211:Treatment Failure
D019380:Anti-HIV Agents; D015684:Gene Products, pol; D017320:HIV Protease Inhibitors; D012367:RNA, Viral