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

J Acquir Immune Defic Syndr. 2011 Sep 1;58(1):1-8. doi: 10.1097/QAI.0b013e318224d0c7.

Abstract

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-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 nor virologic success. Impaired non-HIV antigen-specific lymphoproliferation associated with TI suggests this strategy could be deleterious.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Antigens, Bacterial / immunology
  • Antigens, Fungal / immunology
  • Antigens, Viral / immunology
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Proliferation
  • Drug Administration Schedule
  • Female
  • HIV / immunology*
  • HIV Infections / blood
  • HIV Infections / drug therapy*
  • HIV Infections / immunology*
  • Humans
  • Interferon-gamma / metabolism*
  • Male
  • RNA, Viral / blood
  • Virus Replication

Substances

  • Antigens, Bacterial
  • Antigens, Fungal
  • Antigens, Viral
  • RNA, Viral
  • Interferon-gamma

Grant support