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LB12 Discontinuation of HAART After a Course of Therapeutic Vaccination with ALVAC1452 and rgp160 May Be Associated with Delayed Viral Rebound Kinetics. X. JIN1*, M. RAMANATHAN1, S. BARSOUM1, D. BAUER1, D. CHEN1, A. HURLEY1, B. RAMRATNAM1, J. MURRAY3, R. EL HABIB2, L. ZHANG1, A. PERELSON3, D. D. HO1, and M. MARKOWITZ1. 1Aaron Diamond AIDS Res. Ctr., The Rockefeller Univ., New York, NY; 2Pasteur Merieux Connaught, Lyon, France; and 3Los Alamos National Laboratory, NM. Background: Discontinuation of HAART after suppression of viral replication is associated with rapid rebound within days to weeks with initial doubling times of plasma HIV-1 RNA levels of approximately 1.5 d. Methods: 4 individuals were treated with ZDV/3TC/indinavir 7 to 100 days (median 60 d) after acquiring HIV-1 infection. Median log baseline HIV-1 RNA in plasma was 4.76 (range 3.99 to 6.20). Therapy resulted in prolonged suppression of plasma viremia below the detection level (50 copies/ml) in all subjects. After approx. 2.5 years of therapy, subjects were vaccinated with a course of ALVAC 1452 and recombinant gp160 (see Abst. C53p). After 1162 d of antiviral therapy (range 997 to 1210 d) and 1 week after their final vaccination, these subjects elected to discontinue therapy. Results: In 2 individuals delayed viral rebound was observed, with plasma HIV-1 RNA levels becoming detectable at 68 and 85 d post discontinuation. Initial doubling times for plasma viremia were 4.5 d and 3.2 d. By contrast, the other 2 subjects exhibited rapid viral rebound with detectable viremia within 13 and 23 d post discontinuation. Both were found to have viral doubling times of 1.4 d. Cellular immune responses to HIV-1 antigens were determined serially in all subjects. The “delayed rebounders” had significant increases in CTLe to more than one viral antigen following vaccination. By contrast, one “rapid rebounder” did not mount a measurable CTLe response to the vaccines, whereas the other exhibited a monospecific response to Gag. Currently, “delayed rebounders”, off therapy for 4 and 8 months, have log plasma HIV-1 RNA levels of 3.75 and 2.52, whereas the “rapid rebounders” have levels of 3.55 and >4.70 after 4 months off therapy. Conclusions: These finding, though derived from limited cases, are the first to demonstrate that therapeutic vaccination can enhance cellular immune responses that are temporally associated with suppressed HIV-1 rebound kinetics after discontinuation of HAART. Key Words: |
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© 7th
Conference on Retroviruses and Opportunistic Infections, |