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. Design: We analyzed 59 HIV-1-infected subjects on stable highly active anti retroviral therapy (HAART) therapy (not including zidovudine) with suppress ed plasma viremia (< 400 copies/ml) for phenotypic and lymphoproliferative correlates of immune function. Methods: Peripheral blood mononuclear cells were collected for immunophenot yping, lymphoproliferative assays, and simultaneous immunophenotyping/ultra sensitive in situ hybridization. Plasma was collected for plasma viral load as determined by the Ultra Sensitive Roche Amplicor RT-PCR. Descriptive st atistics (mean and SD, median, first and third quartiles) were determined f or all variables in two groups defined as having persistent viral replicati on present or absent. The two-sided Wilcoxon test (continuity correction, 0 .5) was used to compare lymphocyte phenotypes, lymphoproliferative assay re sponses, intracellular gag-pol mRNA, lowest CD4 counts and CD4% of these tw o 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 greater than or eq ual to 10) compared to patients (n = 35) without persistent intracellular r eplication. The group with persistent HIV-1 replication in cells showed no significant response to the recall antigen tetanus toxoid but a trend towar d higher responses to pathogen antigens. There were no differences between the groups in the prevalence of AIDS or occurrences of opportunistic infect ions; however, the high viral persistence group was more HAART experienced (P < 0.05). Conclusions: These results suggest that HIV-1-specific immune responses cor relate with evidence of ongoing HIV-1 replication. (C) 2001 Lippincott Will iams & Wilkins.