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Impact of Suppression of Viral Replication by Highly Active Antiretroviral Therapy on Immune Function and Phenotype in Chronic HIV-1 Infection

Lange Christoph G.; Lederman, Michael M.; Madero, Juan Sierra; Medvik, Kathy; Asaad, Robert; Pacheko, Christina; Carranza, Claudia; Valdez, Hernan
JAIDS Journal of Acquired Immune Deficiency Syndromes: May 1st, 2002
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We compared immune phenotypes, lymphocyte proliferation (LP), and delayed type hypersensitivity (DTH) responses in 28 male antiretroviral treatmentnaive and experienced HIV-1-infected patients, matched pair-wise according to age and CD4+ T-lymphocyte count. Median CD4+ T-lymphocyte counts were 441 cells/μL and 483 cells/μL and median CD4+ T-lymphocyte nadirs were 435 cells/μL and 150 cells/μL in both groups, respectively. Absolute numbers of circulating T-lymphocyte subpopulations and proportions of naive and memory T-lymphocytes were comparable in the two groups. Untreated patients had greater proportions of activated CD4+ (p < .05) and CD8+ (p < .01) T-cells expressing human leukocyte antigen (HLA)DR and CD38 and fewer CD8+ cells expressing CD28 (p < .05). DTH and LP responses were comparable in both groups except for HIVp24, LP responses, and mumps DTH responses, which were of greater magnitude in the group treated with highly active antiretroviral therapy (HAART) (p < .05).Thus, HIV-1-infected patients who experienced substantial increases in CD4+ T-lymphocyte counts after suppression of viral replication on HAART had fewer activated lymphocytes and similar immune function when compared with findings in untreated patients with similar CD4+ T-cell counts. HIV replication has minimal real time effect on CD4+ T-cell function in response to non-HIV antigens but helper T-cell responses to HIV-gag antigen are impaired during ongoing viral replication and may be restored by antiretroviral therapy.

Address correspondence and reprint requests to Michael M. Lederman; Dept. of Medicine. Div. of Infectious Diseases, University Hospitals of Cleveland, 2061 Cornell Room 301 C, Cleveland, OH 44106 U.S.A.;

Presented in part at the Fifth International Congress on Drug Therapy in HIV Infection, October 22-26, 2000, Glasgow, Scotland.

C. G. Lange is currently affiliated with the Medical Clinic, Research Center Borstel. Borstel. Germany.

Manuscript received November 9. 2001; accepted January 25, 2002.

© 2002 Lippincott Williams & Wilkins, Inc.