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Session 72 Poster Session Treatment Interruption Session Time: 4:30-6:30 pm Room 4E-F

535-M. Effect of Associating a Cytostatic Drug+HAART and Holding the Cytostatic Drug after STI and a Definitive Interruption of HAART on HIV-1-Specific Immune Responses M. Plana*1, L. Lopalco2, F. García1, G. M. Ortiz3, M. J. Maleno1, A. García1, J. Arostegui1, J. Miró1, D. F. Nixon3, C. Gil1, A. Cruceta1, M. Arnedo1, T. Pumarola1, J. Alcami4, F. Lori5, T. Gallart1, and J. M. Gatell1 1Univ. of Barcelona, Spain; 2San Raffaele Sci. Inst., Milan, Italy; 3Univ. of California, San Francisco; 4Inst. Carlos III, Madrid, Spain; and 5Res. Inst. for Genetic and Human Therapy, Georgetown Univ., Washington, DC Background: Our goal was to study the effect of hydroxyurea (HU) vs HU plus ART on HIV-1-specific neutralizing antibodies activity (NA), CTL, and helper responses (LPR) after cycles of STI. Methods: 20 CHI patients (CD4+ > 500/mm3, BVL > 5000 copies/mL) treated with D4T+3TC+IND for 52 weeks were randomized to D4T+DDI+IND (ART group; n=10) vs D4T+DDI+IND+HU (HU group) (n=10) for 24 weeks. Thereafter, 5 STI cycles were performed. HU was discontinued during STI #1, 2, and 3 but held in STI#4 and 5. NA using 2 primary viruses (HIV#40 and HIV#45), LPR to HIV-1 proteins, and CTL responses were assessed. Results: After a median of 48 weeks of follow-up after STI, VL remained <5000 copies/mL (responder patients) in 8/9 patients in HU group and in 4/10 patients in ART group (p= 0.02). By STI #5, there was significant increase in the HIV#45-specific NA from baseline (p=0.003) but no increase in HIV#40-specific NA. The median total CTL response at baseline (BL), and STIs #1-5 were 570, 698, 582, 1080, 1429, 2814 SFC/106 PBMC (p= 0.0001). The breadth of CTL response increased from a median of 3 (range: 0-8) at BL to 6 peptides (range: 4-16) at STI #5. A weak LPR to HIV-1 p24 protein was detected at BL in 3/19 patients and transiently after STI #5 in 14/19 patients (p= 0.0003). No differences were observed between ART and HU groups in NA, CTL and LPR at any time-point. There were no differences in the NA titers at any time-point comparing responder and nonresponder patients. There was a trend for higher CTL, and LPR levels in responder patients (p=0.10). Conclusions: A higher proportion of patients taking HU during on and off ART periods reached a VL set-point < 5000 copies/mL. The increase of NA after STI did not have a role in controlling viral replication. The effect on VL could only be partially attributed to anti-HIV-1 specific cellular immune responses. HU may aid in viral replication control by its own

©2002 9th Conference on Retroviruses and Opportunistic Infections