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Immunologic and virologic response to highly active antiretroviral therapy in the Multicenter AIDS Cohort Study

Yamashita, Traci E.a; Phair, John P.b; Muñoz, Alvaroa; Margolick, Joseph B.a; Detels, Rogerc; O'Brien, Stephen J.d; Mellors, John W.e; Wolinsky, Steven M.b; Jacobson, Lisa P.a

Clinical Science

Objectives: To evaluate prior antiretroviral therapy experience and host characteristics as determinants of immunologic and virologic response to highly active antiretroviral therapy (HAART).

Methods: We studied 397 men from the Multicenter AIDS Cohort Study (MACS) who initiated HAART between October 1995 and March 1999. CD4 cell count and HIV-1 RNA responses to HAART were measured at the first visit following HAART (short-term) and extending from the first visit to approximately 33 months after HAART (long-term). Prior antiretroviral experience was classified into three groups based on antiretroviral therapy use during the 5 years prior to HAART. Age, race and host genetic characteristics also were assessed for their effects on treatment response.

Results: Better short- and long-term CD4 cell and HIV-1 RNA responses were observed in the treatment-naive users. Intermittently and consistently experienced users did not significantly differ in response. Whereas race did not independently affect response, among those initiating HAART with > 400 × 106 CD4 cells/l, younger age and the Δ32 CCR5 genotype were associated with a better short-term CD4 cell response. There was a suggestion that having the protective CCR5 genotype also was associated with a better long-term CD4 cell response.

Conclusion: Immunologic and virologic response to HAART was stronger in individuals who had no prior experience with the antiretroviral therapy agents subsequently included in their initial HAART regimen. Age, level of immune competence and immunogenetics appeared to play a role in the subsequent immune reconstitution following use of highly effective HIV therapy.

From the aJohns Hopkins School of Public Health, Baltimore, Maryland, the bNorthwestern University School of Medicine, Chicago, Illinois, the cUniversity of California, Los Angeles, Schools of Medicine and Public Health, Los Angeles, California, the dNational Cancer Institute-Frederick, Laboratory of Genomic Diversity, Frederick, Maryland and the eUniversity of Pittsburgh and Veterans Affairs Medical Center, Pittsburgh, Pennsylvaina, USA.

Received: 18 August 2000;

revised: 5 January 2001; accepted: 18 January 2001.

Sponsorship: The MACS is funded by The National Institute of Allergy and Infectious Diseases, with additional supplemental funding from the National Cancer Institute. UO1-AI-35042, 5-MO1-RR-00722 (GCRC), UO1-AI-35043, UO1-AI-37984; UO1-AI-35039; UO1-AI-35040, UO1-AI-37613; UO1-AI-35041. Note: Presented in part at the 13th International AIDS Conference, July 2000, Durban, South Africa. Note: Informed consent was obtained from study participants and human experimentation guidelines of the respective institutions conducting the study were followed.

Correspondence to Lisa P. Jacobson, Johns Hopkins University, School of Hygiene and Public Health, Department of Epidemiology, 615 N. Wolfe Street, Room E7006, Baltimore, MD 21205, USA. Tel: +1 410 955 4320; fax: +1 410 955 7587; email: ljacobso@jhsph.edu

© 2001 Lippincott Williams & Wilkins, Inc.