Persistent HIV-1-specific cellular responses despite prolonged therapeutic viral suppression.
METHODS
Antiretroviral therapy (ART) currently represents the best way to avert the lethal consequences of chronic persistent HIV-1 infection. It leads to significant reductions of plasma viremia, often to undetectable levels, but it can also be linked with the reduction and disappearance of detectable HIV-specific CD8 T-cell responses.


RESULTS
Here we describe a group of patients in whom ongoing replication of HIV, particularly transcription of Nef mRNA species, was detected despite prolonged and clinically successful antiretroviral treatment. Modest, but significant, numbers of HIV-specific CD8 T cells and CD4 T-cell responses were found in these subjects, with the strongest responses directed towards Nef epitopes. Detailed phenotypic analysis of the HIV-specific CD8 cells demonstrated low perforin levels and persistent expression of CD27, a phenotype associated with incomplete differentiation of cytotoxic T lymphocytes (CTL).


CONCLUSIONS
This immature CTL phenotype has been described previously in association with chronic HIV disease, but its continued persistence is surprising in the setting of prolonged viral suppression on therapy and the presence of HIV-specific CD4 cell activity.
Appay
Victor
V
Medical Research Council Human Immunology Unit, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK. vappay@gwmail.jr2.ox.ac.uk
Hansasuta
Pokrath
P
Sutton
Julian
J
Schrier
Rachel D
RD
Wong
Joseph K
JK
Furtado
Manohar
M
Havlir
Diane V
DV
Wolinsky
Steven M
SM
McMichael
Andrew J
AJ
Richman
Douglas D
DD
Rowland-Jones
Sarah L
SL
Spina
Celsa A
CA
D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D018106:CD28 Antigens; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D015331:Cohort Studies; D015488:HIV Antigens / Q000276:immunology; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use; D015497:HIV-1 / Q000235:genetics / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D019469:Indinavir / Q000627:therapeutic use; D007371:Interferon-gamma / Q000276:immunology; D019259:Lamivudine / Q000627:therapeutic use; D008562:Membrane Glycoproteins; D014066:Palatine Tonsil / Q000166:cytology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
D019380:Anti-HIV Agents; D018106:CD28 Antigens; D015488:HIV Antigens; D017320:HIV Protease Inhibitors; D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D054353:Perforin; D019259:Lamivudine; D019469:Indinavir; D007371:Interferon-gamma