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

Alan Landay, Barbara A. Da Silva, Martin S. King, Mary Albrecht, Constance Benson, Joseph Eron, Marshall Glesby, Roy Gulick, Charles Hicks, Harold Kessler, Robert Murphy, Melanie Thompson, A. Clinton White, Peter Wolfe, Florence I. McMillan, George J. Hanna

Research output: Contribution to journalArticle

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Abstract

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 lopinavirritonavir, 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/ftL (P < .001), 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 (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.

Original languageEnglish (US)
Pages (from-to)749-754
Number of pages6
JournalClinical Infectious Diseases
Volume44
Issue number5
DOIs
StatePublished - Mar 1 2007
Externally publishedYes

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Lopinavir
Ritonavir
HIV-1
T-Lymphocytes
RNA
CD4 Lymphocyte Count
Therapeutics
Cell Count
Stavudine
Lamivudine
Highly Active Antiretroviral Therapy
T-Lymphocyte Subsets
Natural Killer Cells
Sustained Virologic Response
Flow Cytometry
B-Lymphocytes
Biomarkers

ASJC Scopus subject areas

  • Immunology

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Evidence of ongoing immune reconstitution in subjects with sustained viral suppression following 6 years of lopinavir-ritonavir treatment. / Landay, Alan; Da Silva, Barbara A.; King, Martin S.; Albrecht, Mary; Benson, Constance; Eron, Joseph; Glesby, Marshall; Gulick, Roy; Hicks, Charles; Kessler, Harold; Murphy, Robert; Thompson, Melanie; White, A. Clinton; Wolfe, Peter; McMillan, Florence I.; Hanna, George J.

In: Clinical Infectious Diseases, Vol. 44, No. 5, 01.03.2007, p. 749-754.

Research output: Contribution to journalArticle

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 2007, 'Evidence of ongoing immune reconstitution in subjects with sustained viral suppression following 6 years of lopinavir-ritonavir treatment', Clinical Infectious Diseases, vol. 44, no. 5, pp. 749-754. https://doi.org/10.1086/511681
Landay, Alan ; Da Silva, Barbara A. ; King, Martin S. ; Albrecht, Mary ; Benson, Constance ; Eron, Joseph ; Glesby, Marshall ; Gulick, Roy ; Hicks, Charles ; Kessler, Harold ; Murphy, Robert ; Thompson, Melanie ; White, A. Clinton ; Wolfe, Peter ; McMillan, Florence I. ; Hanna, George J. / Evidence of ongoing immune reconstitution in subjects with sustained viral suppression following 6 years of lopinavir-ritonavir treatment. In: Clinical Infectious Diseases. 2007 ; Vol. 44, No. 5. pp. 749-754.
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abstract = "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 lopinavirritonavir, 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/ftL (P < .001), 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 (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.",
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T1 - Evidence of ongoing immune reconstitution in subjects with sustained viral suppression following 6 years of lopinavir-ritonavir treatment

AU - Landay, Alan

AU - Da Silva, Barbara A.

AU - King, Martin S.

AU - Albrecht, Mary

AU - Benson, Constance

AU - Eron, Joseph

AU - Glesby, Marshall

AU - Gulick, Roy

AU - Hicks, Charles

AU - Kessler, Harold

AU - Murphy, Robert

AU - Thompson, Melanie

AU - White, A. Clinton

AU - Wolfe, Peter

AU - McMillan, Florence I.

AU - Hanna, George J.

PY - 2007/3/1

Y1 - 2007/3/1

N2 - 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 lopinavirritonavir, 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/ftL (P < .001), 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 (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.

AB - 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 lopinavirritonavir, 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/ftL (P < .001), 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 (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.

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