Augmented HIV-specific interferon-gamma responses, but impaired lymphoproliferation during interruption of antiretroviral treatment initiated in primary HIV infection.

TitleAugmented HIV-specific interferon-gamma responses, but impaired lymphoproliferation during interruption of antiretroviral treatment initiated in primary HIV infection.
Publication TypeJournal Article
Year of Publication2011
AuthorsConnick E, Bosch RJ, Aga E, Schlichtemeier R, Demeter LM, Volberding P
Corporate AuthorsACTG 709 Team
JournalJ Acquir Immune Defic Syndr
Volume58
Issue1
Pagination1-8
Date Published2011 Sep 1
ISSN1944-7884
KeywordsAdult, Antigens, Bacterial, Antigens, Fungal, Antigens, Viral, CD8-Positive T-Lymphocytes, Cell Proliferation, Drug Administration Schedule, Female, HIV, HIV Infections, Humans, Interferon-gamma, Male, RNA, Viral, Virus Replication
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.

DOI10.1097/QAI.0b013e318224d0c7
Alternate JournalJ. Acquir. Immune Defic. Syndr.
PubMed ID21637110
PubMed Central IDPMC3159837
Grant ListAI 69450 / AI / NIAID NIH HHS / United States
AI-069511 / AI / NIAID NIH HHS / United States
AI-38855 / AI / NIAID NIH HHS / United States
AI-38858 / AI / NIAID NIH HHS / United States
AI-68634 / AI / NIAID NIH HHS / United States
AI-68636 / AI / NIAID NIH HHS / United States
AI-69432 / AI / NIAID NIH HHS / United States
P30 AI027763 / AI / NIAID NIH HHS / United States
U01 AI038855 / AI / NIAID NIH HHS / United States
U01 AI038855-04 / AI / NIAID NIH HHS / United States
U01 AI038855-05 / AI / NIAID NIH HHS / United States
U01 AI038855-06 / AI / NIAID NIH HHS / United States
U01 AI038855-07 / AI / NIAID NIH HHS / United States
U01 AI038858 / AI / NIAID NIH HHS / United States
U01 AI038858-04 / AI / NIAID NIH HHS / United States
U01 AI038858-05 / AI / NIAID NIH HHS / United States
U01 AI038858-06 / AI / NIAID NIH HHS / United States
U01 AI038858-07 / AI / NIAID NIH HHS / United States
U01 AI038858-08 / AI / NIAID NIH HHS / United States
U01 AI038858-09 / AI / NIAID NIH HHS / United States
U01 AI038858-09S1 / AI / NIAID NIH HHS / United States
U01 AI038858-09S2 / AI / NIAID NIH HHS / United States
U01 AI038858-09S3 / AI / NIAID NIH HHS / United States
U01 AI038858-09S4 / AI / NIAID NIH HHS / United States
U01 AI068634 / AI / NIAID NIH HHS / United States
U01 AI068634-01 / AI / NIAID NIH HHS / United States
U01 AI068634-02 / AI / NIAID NIH HHS / United States
U01 AI068634-03 / AI / NIAID NIH HHS / United States
U01 AI068634-04 / AI / NIAID NIH HHS / United States
U01 AI068634-05 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
U01 AI068636-01 / AI / NIAID NIH HHS / United States
U01 AI068636-02 / AI / NIAID NIH HHS / United States
U01 AI068636-03 / AI / NIAID NIH HHS / United States
U01 AI068636-04 / AI / NIAID NIH HHS / United States
U01 AI068636-04S1 / AI / NIAID NIH HHS / United States
U01 AI069432 / AI / NIAID NIH HHS / United States
U01 AI069432-01 / AI / NIAID NIH HHS / United States
U01 AI069432-02 / AI / NIAID NIH HHS / United States
U01 AI069432-03 / AI / NIAID NIH HHS / United States
U01 AI069432-04 / AI / NIAID NIH HHS / United States
U01 AI069432-05 / AI / NIAID NIH HHS / United States
U01 AI069432-06 / AI / NIAID NIH HHS / United States
U01 AI069450 / AI / NIAID NIH HHS / United States
U01 AI069450-01 / AI / NIAID NIH HHS / United States
U01 AI069450-02 / AI / NIAID NIH HHS / United States
U01 AI069450-03 / AI / NIAID NIH HHS / United States
U01 AI069450-04 / AI / NIAID NIH HHS / United States
U01 AI069450-05 / AI / NIAID NIH HHS / United States
U01 AI069450-06 / AI / NIAID NIH HHS / United States
U01 AI069502 / AI / NIAID NIH HHS / United States
U01 AI069502-01 / AI / NIAID NIH HHS / United States
U01 AI069502-02 / AI / NIAID NIH HHS / United States
U01 AI069502-03 / AI / NIAID NIH HHS / United States
U01 AI069502-04 / AI / NIAID NIH HHS / United States
U01 AI069502-05 / AI / NIAID NIH HHS / United States
U01 AI069502-06 / AI / NIAID NIH HHS / United States
U01 AI069511 / AI / NIAID NIH HHS / United States
U01 AI069511-02 / AI / NIAID NIH HHS / United States
U01 AI069511-03 / AI / NIAID NIH HHS / United States
U01 AI069511-04 / AI / NIAID NIH HHS / United States
U01 AI069511-04S1 / AI / NIAID NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068634-06 / AI / NIAID NIH HHS / United States
UM1 AI069511 / AI / NIAID NIH HHS / United States