Effects of highly active antiretroviral therapy and immune recovery on CD8+ T-cell-mediated inhibition of HIV-1 transcription.
: To date, the relation between the CD8 antiviral factor (CAF) and clinical indicators of disease progression in HIV-1 infection (CD4 T-cell counts and viral load [VL]) is inconclusive. Particularly, the effect of antiretroviral therapy and immune recovery on CAF production remains unclear. Using a transient transfection assay and a reporter gene activated by the HIV-1 long terminal repeat (LTR), we analyzed CAF production in CD8 T cells of HIV-1-positive individuals divided into 3 groups: patients on protease inhibitor (PI)-based therapy, patients on nonnucleoside reverse transcriptase inhibitor (NNRTI)-based therapy, and patients receiving no therapy. We found that within the untreated group, CAF activity inversely correlated with VL and high CAF was associated with lower VLs over a period of 0.5 to 3 years. Furthermore, patients who were drug-naive demonstrated significantly higher CAF than untreated patients who had previously undergone antiretroviral therapy. CAF activity in treated patients was similar to CAF in drug-naive patients and higher than in off-treatment patients. There seemed to be a trend toward higher CAF in patients on NNRTI-based therapy compared with those on PI-based therapy. These results suggest that immune recovery after highly active antiretroviral therapy (HAART) contributes to the normalization of CAF levels in HIV-1-positive individuals. Furthermore, we have distinguished between CD8 T-cell-mediated suppression of HIV-1 replication and gene transcription.
Beaudoin
Greg
G
Molecular Medicine Program, Ottawa Health Research Institute, 501 Smyth Road, Ottawa, Ontario, Canada.
Diker
Bilge
B
Angel
Jonathan B
JB
Copeland
Karen F T
KF
D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D000998:Antiviral Agents / Q000097:blood* / Q000494:pharmacology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology*; D016325:HIV Long Terminal Repeat / Q000187:drug effects; D015497:HIV-1 / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D006801:Humans; D019169:Jurkat Cells / Q000821:virology; D011480:Protease Inhibitors / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use; D014158:Transcription, Genetic / Q000187:drug effects*; D016896:Treatment Outcome; D019562:Viral Load; D014779:Virus Replication
D019380:Anti-HIV Agents; D000998:Antiviral Agents; D011480:Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors