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

• Published in: The Journal of infectious diseases Vol. 181; no. 5; pp. 1808 - 1812
• Main Authors: Bélec, Laurent, Piketty, Christophe, Si-Mohamed, Ali, Goujon, Christophe, Hallouin, Marie-Charlotte, Cotigny, Sylvie, Weiss, Laurence, Kazatchkine, Michel D.
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 01.05.2000; University of Chicago Press
• Subjects: AIDS/HIV; Amino Acid Sequence; Anti-HIV Agents - therapeutic use; Biological and medical sciences; CD4 Lymphocyte Count; Concise Communications; Drug Resistance, Microbial; Drug Therapy, Combination; Gene Products, pol - chemistry; Gene Products, pol - genetics; Genes, pol; Genetic mutation; Highly active antiretroviral therapy; HIV; HIV 1; HIV Infections - drug therapy; HIV Infections - immunology; HIV Infections - virology; HIV Protease Inhibitors - therapeutic use; HIV-1 - drug effects; HIV-1 - genetics; HIV-1 - isolation & purification; Human viral diseases; Humans; Immunology; Infectious diseases; Medical sciences; Mutation; Protease inhibitors; RNA; RNA, Viral - blood; Sequence Alignment; Sequence Homology, Amino Acid; T lymphocytes; Time Factors; Transponders; Treatment Failure; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Virology; Human; Immunopathology; Drug combination; Genetic variant; Retroviridae; AIDS; Immune deficiency; Lentivirus; Infection; Virus; Chemotherapy; Sensitivity resistance; Treatment; Viral disease; Antiviral; Mutation; Human immunodeficiency virus
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/315429

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.