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Evidence of ongoing immune reconstitution in subjects with sustained viral suppression following 6 years of lopinavir-ritonavir treatment.

Landay A, da Silva BA, King MS, Albrecht M, Benson C, Eron J, Glesby M, Gulick R, Hicks C, Kessler H, Murphy R, Thompson M, White AC, Wolfe P, McMillan FI, Hanna GJ

Dept. of Immunology/Microbiology, Rush University Medical Center, Chicago, IL 60612, USA. alanday@rush.edu

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/microL (P<.001), and 81% of subjects had CD4+ T cell counts >500 cells/microL, 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 (P<.001). 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.

Published 5 February 2007 in Clin Infect Dis, 44(5): 749-54.
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