Augmented HIV-Specific Interferon-Gamma Responses, But Impaired Lymphoproliferation During Interruption of Antiretroviral Treatment Initiated in Primary HIV Infection

作者：Connick Elizabeth^*; Bosch Ronald J; Aga Evgenia; Schlichtemeier Rick; Demeter Lisa M; Volberding Paul

来源：JAIDS: Journal of Acquired Immune Deficiency Syndromes , 2011, 58(1): 1-8.

DOI：10.1097/QAI.0b013e318224d0c7

• CD4-positive T lymphocytes
• CD8-positive T lymphocytes
• cytotoxic T lymphocytes
• HIV infections
• highly active antiretroviral therapy
• treatment interruption

Background: Antiretroviral therapy (ART) introduced during primary HIV infection followed by treatment interruption (TI) is postulated to enhance virologic control through induction of HIV-specific CD4(+) T cells, which foster virus-specific CD8+ T cells that suppress virus replication. This hypothesis was evaluated in 21 subjects enrolled in AIDS Clinical Trials Group 709, a substudy of AIDS Clinical Trials Group 371, which prospectively evaluated subjects who received >= 1 year of ART initiated in acute or recent HIV infection followed by TI.
Methods: Lymphoproliferation was assessed by [methyl-(3)H] thymidine incorporation and HIV-specific CD8+ T-cell interferon-gamma responses by enzyme-linked immunospot-forming assays. Virologic success was defined as sustained viral load <5000 copies per milliliter for 24 weeks after TI.
Results: HIV-specific lymphoproliferative responses were detected at least once in 5 (24%) of 21 subjects, were generally transient, and were unrelated to HIV-specific interferon-gamma responses (P>0.4). HIV-specific CD8+ interferon-gamma responses increased after 48 weeks of ART (P = 0.03), but failed to predict virologic success (P = 0.18). Compared with seronegative subjects, lymphoproliferation to Candida, cytomegalovirus, and alloantigens was similar in HIV-infected subjects during ART, but lower during TI (P <= 0.04).
Conclusions: HIV-specific CD8+ T-cell interferon-gamma responses expand during ART following primary HIV infection, but are not related to HIV-specific lymphoproliferative responses norvirologic success. Impaired non-HIV antigen-specific lymphoproliferation associated with TI suggests this strategy could be deleterious.

• 出版日期2011-9-1