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

Clin Infect Dis. 2007 Mar 1;44(5):749-54. doi: 10.1086/511681. Epub 2007 Jan 25.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use*
  • Biomarkers
  • CD4-CD8 Ratio
  • Clinical Trials, Phase II as Topic
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • HIV Infections / drug therapy*
  • HIV Infections / immunology*
  • HIV Infections / virology
  • HIV-1* / genetics
  • HIV-1* / isolation & purification
  • Humans
  • Lamivudine / therapeutic use
  • Lopinavir
  • Male
  • Middle Aged
  • Pyrimidinones / therapeutic use*
  • RNA, Viral / blood
  • Ritonavir / therapeutic use*
  • Stavudine / therapeutic use

Substances

  • Anti-HIV Agents
  • Biomarkers
  • Pyrimidinones
  • RNA, Viral
  • Lopinavir
  • Lamivudine
  • Stavudine
  • Ritonavir