Persistence of intracellular HIV-1 mRNA correlates with HIV-1-specific immune responses in infected subjects on stable HAART.
OBJECTIVE
To determine if low level, persistent, HIV-1 replication within specific immune cells contributes to HIV-1-specific immune responsiveness.


METHODS
We analyzed 59 HIV-1-infected subjects on stable highly active antiretroviral therapy (HAART) therapy (not including zidovudine) with suppressed plasma viremia (< 400 copies/ml) for phenotypic and lymphoproliferative correlates of immune function.


METHODS
Peripheral blood mononuclear cells were collected for immunophenotyping, lymphoproliferative assays, and simultaneous immunophenotyping/ultrasensitive in situ hybridization. Plasma was collected for plasma viral load as determined by the Ultra Sensitive Roche Amplicor RT-PCR. Descriptive statistics (mean and SD, median, first and third quartiles) were determined for all variables in two groups defined as having persistent viral replication present or absent. The two-sided Wilcoxon test (continuity correction, 0.5) was used to compare lymphocyte phenotypes, lymphoproliferative assay responses, intracellular gag-pol mRNA, lowest CD4 counts and CD4% of these two groups.


RESULTS
HIV-1 replication in CD4, CD45RO memory T lymphocytes persists in spite of undetectable plasma viral load. Patients (n = 24) with persistent intracellular expression of HIV-1 mRNA (> 0.3%) showed significant in vitro proliferative responses to HIV-1 p24 (stimulation index > or = 10) compared to patients (n = 35) without persistent intracellular replication. The group with persistent HIV-1 replication in cells showed no significant response to the recall antigen tetanus toxoid but a trend toward higher responses to pathogen antigens. There were no differences between the groups in the prevalence of AIDS or occurrences of opportunistic infections; however, the high viral persistence group was more HAART experienced (P < 0.05).


CONCLUSIONS
These results suggest that HIV-1-specific immune responses correlate with evidence of ongoing HIV-1 replication.
Patterson
B K
BK
Department of Pediatrics, Division of Infectious Diseases, Children's Memorial Hospital/Northwestern University Medical School, Chicago, Illinois 60614, USA.
McCallister
S
S
Schutz
M
M
Siegel
J N
JN
Shults
K
K
Flener
Z
Z
Landay
A
A
D023241:Antiretroviral Therapy, Highly Active; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D006801:Humans; D016130:Immunophenotyping; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008213:Lymphocyte Activation; D012333:RNA, Messenger / Q000097:blood*; D012367:RNA, Viral / Q000097:blood; D019562:Viral Load; D014779:Virus Replication
D012333:RNA, Messenger; D012367:RNA, Viral; D017493:Leukocyte Common Antigens