356   Influence of Hydroxyurea (HU) Associated with HAART and Maintained During Periods Off Antiretroviral Therapy in STI on the HIV-1-Specific Immune Responses.

M. Plana*¹, F. García¹, G. M. Ortiz², C. Martínez¹, A. Soriano¹, M. J. Maleno¹, A. García¹, M. Lejeune¹, T. Gallart¹, D. F. Nixon², J. M. Miró¹, and J. M. Gatell¹.
¹Barcelona, Spain and²New York, NY.

Background:Our objective to analyse if the association of HU with HAART maintaining HU during periods off therapy in STI could affect the specific HIV-1 immune responses.

Methods:20 CHI patients treated with D4T + 3TC + IND for 52 weeks and VL <20 c/ml for at least 32 weeks were randomized to receive D4T + DDI + IND + HU (HU group) (n = 10) vs D4T + DDI + IND (ART group) (n = 10) during 6 months. Thereafter, 5 consecutive cycles of STI were undertaken separated by periods of 2 months with the same HAART (which was reintroduced when VL increased >200 c/ml in the 1st stop, after 2 weeks in the 2nd, 3rd and 4th stops, and after VL reached a set-point after the 5th stop). HU was discontinued during the 3 first periods off ART and maintained in the 4th and 5th (and last) stops. We measured plasma VL, CD4⁺lymphocyte proliferative responses to HIV-1 proteins and HIV-1-specific CTL responses, measured by ELISPOT using a panel of HLA class I-restricted peptides from gag, pol, env and nef proteins.

Results:At baseline, only 3 out of 9 patients in the ART group and 4 out of 8 patients in the HU group showed a moderate to strong CTL response to a mean of 3 peptides (range: 0—8). An increase in magnitude and breadth of the CTL response was observed after the consecutive periods of STI (after the 3rd stop, 7 out 9 patients in the ART group and 7 out of 8 patients in the HU group had a moderate to strong CTL response to a mean of 6 peptides). During the 4th and 5th stops, 6 out of 8 patients in the ART group and 5 out of 5 patients in the HU group maintained a moderate to strong CTL response. Likewise, after the 4th stop, 9 out of 10 patients in the ART group and 8 out of 9 patients in the HU group developed a proliferative response to HIV-1 p24 protein (present at baseline in only 1 out of 10 patients in the ART group and in 2 out of 9 patients in the HU group). During the 5th and last stop, 1 out of 6 patients in the ART group and 5 out of 5 patients in the HU group maintained the CD4⁺HIV-1-specific response.

Conclusions:These data suggest that HU associated with HAART and maintained during the periods of STI has no deleterious effects on both the HIV-1-specific CTL and helper responses.