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 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.
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 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.
Authors: Tae-Wook Chun; David C Nickle; J Shawn Justement; Danielle Large; Alice Semerjian; Marcel E Curlin; M Angeline O'Shea; Claire W Hallahan; Marybeth Daucher; Douglas J Ward; Susan Moir; James I Mullins; Colin Kovacs; Anthony S Fauci Journal: J Clin Invest Date: 2005-11 Impact factor: 14.808
Authors: Phalguni Gupta; Kelly B Collins; Deena Ratner; Simon Watkins; Gregory J Naus; Daniel V Landers; Bruce K Patterson Journal: J Virol Date: 2002-10 Impact factor: 5.103
Authors: Tae-Wook Chun; J Shawn Justement; Richard A Lempicki; Jun Yang; Glynn Dennis; Claire W Hallahan; Christina Sanford; Punita Pandya; Shuying Liu; Mary McLaughlin; Linda A Ehler; Susan Moir; Anthony S Fauci Journal: Proc Natl Acad Sci U S A Date: 2003-01-27 Impact factor: 11.205
Authors: Amy E Baxter; Julia Niessl; Rémi Fromentin; Jonathan Richard; Filippos Porichis; Roxanne Charlebois; Marta Massanella; Nathalie Brassard; Nirmin Alsahafi; Gloria-Gabrielle Delgado; Jean-Pierre Routy; Bruce D Walker; Andrés Finzi; Nicolas Chomont; Daniel E Kaufmann Journal: Cell Host Microbe Date: 2016-08-18 Impact factor: 21.023