AEGiS-14IAC: HIV-specific immune responses in subjects stopping antiretrovirals (AR) after HAART intensification, macrophage stimulation and initiation of therapeutic vaccination (Remune) in chronic HIV infection. CTN 140 study.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

HIV-specific immune responses in subjects stopping antiretrovirals (AR) after HAART intensification, macrophage stimulation and initiation of therapeutic vaccination (Remune) in chronic HIV infection. CTN 140 study.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. A10086)

Bernard NF, Chung F, Merchant A, Loignon M, Zarowny D, Toma E
McGill University Health Center, Montreal, Canada

BACKGROUND: In chronically HIV-infected adults HAART results in significant clinical and immunologic benefits but does not prevent viral rebound when interrupted. Hypothesis: Intensification of an optimal HAART, use of GM-CSF and Remune before stopping HAART might boost HIV-specific immunity and lead to a partial containment of viremia allowing for long periods off HAART.

METHODS: Ten adults (median age: 41 years) with chronic HIV infection, on HAART for a median of 2.7 years, with HIV RNA levels (VL) <50 copies/ml for a median of 2 years and median CD4+ T cell count of 385/ml were enrolled in this trial. After a 6-month HAART intensification with ddI, hydroxyurea (HU)( x 5 months), GM-CSF (first 3 months) and a dose of Remune they stopped HAART but continued to receive Remune every 3 months. HAART and HU were resumed if rebounded VL did not decreased to <50 000 copies within 3 months or if the CD4+counts decreased to <200 cells/ml. Interferon-[gamma] (IFN-γ) Elispot, intracellular cytokine staining for IFN-γ secretion from CD4+ and CD8+ T cells were used to measure HIV-specific immunity longitudinally.

RESULTS: Scheduled treatment interruption (STI) resulted in viral rebound in all subjects. The average breadth of HIV-specific response contracted significantly during therapy intensification but expanded thereafter. The average magnitude of the response to either a panel of HLA restricted optimal HIV peptides or a pool of peptides corresponding to Gag increased 2 to 3 fold from pre-STI to 3 to 9 months after STI levels. This trend in increased magnitude did not achieve statistical significance.

CONCLUSIONS: Although the breadth and magnitude of HIV-specific effector activity increased following the first round of STI in this population this rise did not appear to prevent viral rebound.

Keywords: AEGIS, Antiretroviral Therapy, Highly Active, HIV, HIV Infections, AIDS Vaccines, Acquired Immunodeficiency Syndrome, CD4 Lymphocyte Count, Anti-HIV Agents, Didanosine, HIV Seropositivity, Vaccination, HIV Protease Inhibitors, Viremia, Hydroxyurea, remune, Adult, therapy, drug therapy

020707
A10086