Evidence of ongoing immune reconstitution in subjects with sustained viral suppression following 6 years of lopinavir-ritonavir treatment.
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.
Landay
Alan
A
Dept. of Immunology/Microbiology, Rush University Medical Center, Chicago, IL 60612, USA. alanday@rush.edu
da Silva
Barbara A
BA
King
Martin S
MS
Albrecht
Mary
M
Benson
Constance
C
Eron
Joseph
J
Glesby
Marshall
M
Gulick
Roy
R
Hicks
Charles
C
Kessler
Harold
H
Murphy
Robert
R
Thompson
Melanie
M
White
A Clinton
AC
Wolfe
Peter
P
McMillan
Florence I
FI
Hanna
George J
GJ
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D015415:Biomarkers; D016516:CD4-CD8 Ratio; D017322:Clinical Trials, Phase II as Topic; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D061466:Lopinavir; D008297:Male; D008875:Middle Aged; D011744:Pyrimidinones / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000627:therapeutic use*; D018119:Stavudine / Q000627:therapeutic use
D019380:Anti-HIV Agents; D015415:Biomarkers; D011744:Pyrimidinones; D012367:RNA, Viral; D061466:Lopinavir; D019259:Lamivudine; D018119:Stavudine; D019438:Ritonavir