Low CD4+ T-cell counts in HIV patients receiving effective antiretroviral therapy are associated with CD4+ T-cell activation and senescence but not with lower effector memory T-cell function.
The adverse effects of immune activation on CD4(+) T-cell recovery and the relationship between CD4(+) T-cell counts and effector T-cell function were examined in HIV-1 patients receiving long-term effective ART. Patients with nadir CD4(+) T-cell counts <100/microl, > 12 months on ART and >6 months with <50 HIV RNA copies/ml were stratified by current CD4(+) T-cell counts and patients from the lowest (n = 15) and highest (n = 12) tertiles were studied. We assessed proliferation (Ki67), activation (HLA-DR, CD38) and replicative senescence (CD57) by flow cytometry and CD4(+) T-cell responses to CMV by IFN-gamma ELISpot. Proportions of CD4(+) T-cells expressing HLA-DR or CD57 were strong univariate predictors of total (P = 0.0002 and P = 0.002) and naive (P < 0.0001 and P < 0.0001, respectively) CD4(+) T-cell counts, suggesting that CD4(+) T-cell activation drives the depletion of naive CD4(+) T-cells. This was clearest in patients with a small/undetectable thymus. IFN-gamma responses to CMV were similar in patients with low or high CD4(+) T-cell counts.
Fernandez
Sonia
S
Department of Clinical Immunology and Biochemical Genetics, Royal Perth Hospital, Perth, Australia.
Price
Patricia
P
McKinnon
Elizabeth J
EJ
Nolan
Richard C
RC
French
Martyn A
MA
D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000276:immunology* / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D049109:Cell Proliferation; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D009929:Organ Size; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology / Q000473:pathology
D019380:Anti-HIV Agents; D015415:Biomarkers