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1 March 2007

Volume 44, Number 5
Clinical Infectious Diseases 2007;44:749–754
© 2007 by the Infectious Diseases Society of America. All rights reserved.
1058-4838/2007/4405-0021$15.00
DOI: 10.1086/511681
HIV/AIDS MAJOR ARTICLE

Evidence of Ongoing Immune Reconstitution in Subjects with Sustained Viral Suppression following 6 Years of Lopinavir‐Ritonavir Treatment

Alan Landay,1

Barbara A. da Silva,3

Martin S. King,3

Mary Albrecht,4

Constance Benson,5

Joseph Eron,7

Marshall Glesby,9

Roy Gulick,5

Charles Hicks,8

Harold Kessler,1

Robert Murphy,2

Melanie Thompson,10

A. Clinton White, Jr.,11

Peter Wolfe,6

Florence I. McMillan,3 and

George J. Hanna3

1Rush University Medical Center and 2Northwestern University, Chicago, and 3Abbott Laboratories, Abbott Park, Illinois; 4Harvard University, Boston, Massachusetts; 5University of California, San Diego, and 6Pacific Oaks Research, San Francisco, California; 7University of North Carolina, Chapel Hill, and 8Duke University Medical Center, Durham, North Carolina; 9Weill Medical College of Cornell University, New York, New York; 10AIDS Research Consortium of Atlanta, Atlanta, Georgia; and 11Baylor College of Medicine, Houston, Texas

Background.We evaluated the immunologic impact of highly active antiretroviral therapy in subjects who maintained human immunodeficiency virus type 1 (HIV‐1) suppression through 6 years of receiving a lopinavir‐ritonavir–based regimen.

Methods.A total of 100 antiretroviral‐naive subjects with any CD4+ T cell count initiated therapy with lopinavir‐ritonavir, stavudine, and lamivudine. Sixty‐three subjects who remained in the study for 6 years were assessed. Laboratory measurements included plasma HIV‐1 RNA levels, multiparameter flow cytometry of immune cells, and markers of maturation and activation.

Results.After 6 years, 62 of 63 subjects had plasma HIV‐1 RNA levels <50 copies/mL. The mean increase in CD4+ T cell count was 528 cells/μL ( ), and 81% of subjects had CD4+ T cell counts >500 cells/μL, compared with 21% of subjects at baseline. The mean ratio of CD4+ T cell count to CD8+ T cell count increased from 0.38 at baseline to 0.96 at year 6 ( ). The percentage of subjects with cell counts below the lower limit of normal at year 6, compared with at baseline, was significantly decreased for total T cells, B cells, and natural killer cells. At year 6, the median CD4+ T cell activation level was 3.4%, and the median CD8+ T cell activation level was 5.8%.

Conclusions.The receipt of a lopinavir‐ritonavir–based regimen resulted in ongoing immune reconstitution through 6 years of therapy in a cohort of HIV‐1–infected, antiretroviral‐naive subjects with suppressed HIV‐1 RNA levels. Normalization of activation marker expression on CD4+ and CD8+ T cell subsets was demonstrated.

Received 20 July 2006; accepted 7 November 2006; electronically published 25 January 2007.

Reprints or correspondence: Dr. Alan L. Landay, Dept. of Immunology/Microbiology, Dept. of Medicine, Rush University Medical Center, 1735 W. Harrison St., Rm. 616, Cohn Bldg., Chicago, IL 60612 ().

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  • Presented in part: 3rd International AIDS Society Conference on HIV Pathogenesis and Treatment, Rio de Janeiro, Brazil, 2005 (poster WePE 16.7B04); 14th International AIDS Conference, Barcelona, Spain, 2002 (poster TUPeB4439).

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