High levels of drug-resistant human immunodeficiency virus variants in patients exhibiting increasing CD4+ T cell counts despite virologic failure ofprotease 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 ac tive antiretroviral therapy (HAART), despite virologic failure of treatment . After 12 months of HAART, 1 or 2 primary resistance mutations had occurre d in 18 (66%) of the patients, and secondary mutations had accumulated in 2 2 (88%) of the patients. The number and patterns of mutations in the patien ts who exhibited discrepant responses to HAART did not differ from those ob served in patients who exhibited immunologic and virologic failure to thera py. Results indicate that many patients have prolonged immunologic benefits , despite the development of virologic failure and protease inhibitor mutat ions. 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.