Proliferation responses to HIVp24 during antiretroviral therapy do not reflect improved immune phenotype or function.
OBJECTIVE
To ascertain whether lymphoproliferation (LP) responses to HIVp24 in chronically infected patients treated with antiretroviral therapy (ART) predict an improved cytolytic T-cell phenotype or better in vivo immune function as measured by immunization responses.


METHODS
HIV-infected patients who started ART during chronic infection and who achieved viral suppression (HIV-RNA < 400 copies/ml for > 12 months) were grouped by the presence of strong [stimulation index (SI) > 10; n = 21] or absent (SI < 3; n = 18) LP to HIV-core antigen. The two groups were compared for functional immune responses to vaccination with diphtheria-toxoid, tetanus-toxoid and keyhole-limpet-hemocyanin, frequency of circulating naive and memory CD4+ and CD8+ T lymphocytes, maturation phenotype and expression of cytolytic molecules on total and HIV-specific CD8+ T cells, and frequency of memory CD4+ T cells with intracellular HIV-mRNA. Group comparisons were analyzed by non-parametric Mann-Whitney tests. Proportions were estimated by Pearson's chi analysis.


RESULTS
There were no differences between the groups in immune responses to vaccination or in the numbers or phenotype of circulating T cells. In a subgroup of HLA-A2+ or B8+ patients, HIV-reactive CD8+ T cells in both groups had similar expression of perforin, granzyme A and T-cell maturation markers (CD27, CD28, CCR7, CD62L). However, patients with SI > 10 in response to HIVp24 tended to more often have high levels of circulating CD4+ T cells with intracellular HIV-1 mRNA than did patients with SI < 3.


CONCLUSIONS
Following long-standing suppression of viral replication on ART, the presence of HIV-1 specific T-helper proliferation responses does not correlate with improved indices of immune phenotype or function but may reflect relatively higher levels of HIV-expression.
Lange
Christoph G
CG
Center for AIDS Research, Department of Medicine, Division of Infectious Diseases, Case Western Reserve University, University Hospitals of Cleveland, 2061 Cornell Road, Cleveland, OH 44106, USA.
Xu
Zhan
Z
Patterson
Bruce K
BK
Medvik
Kathy
K
Harnisch
Brooke
B
Asaad
Robert
R
Valdez
Hernan
H
Lee
Sandra J
SJ
Landay
Alan
A
Lieberman
Judy
J
Lederman
Michael M
MM
D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002908:Chronic Disease; D016655:HIV Core Protein p24 / Q000276:immunology*; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D006801:Humans; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology; D008875:Middle Aged; D012367:RNA, Viral / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014611:Vaccination; D014779:Virus Replication
D016655:HIV Core Protein p24; D012367:RNA, Viral