359   HIV-1-Specific T-Cell Responses and Spontaneous Control of Viremia Can Be Detected after the First Cycle of Structured Treatment Interruptions (STI) in Patients Receiving HAART since Primary HIV-1 Infection (PHI).

J. M. Miro*¹, C. Tortajada¹, M. Plana¹, G. M. Ortiz², M. J. Maleno¹, M. Arnedo¹, L. Lozano¹, C. Vidal¹, A. Garcia¹, T. Pumarola¹, D. Nixon², T. Gallart¹, F. Garcia¹, and J. M. Gatell¹.
¹Hosp. Clín. Univ. Barcelona, Spain and²Aaron Diamond AIDS Res. Ctr., The Rockefeller Univ., New York, NY.

Background:Our objective was to analyze if STI can restore HIV-1-specific T-cell responses (CD4⁺

CTL) and control HIV-1 replication in patients who started HAART within 90 days after onset of symptoms of PHI. We analyzed the dynamics of plasma HIV-1 RNA viral load (PVL) rebound and the HIV-1-specific T-cell responses after the first STI cycle.

Methods:12 consecutive patients with sustained viral suppression (<20 copies/mL) and a CD4⁺/ CD8⁺ratio >1 after receiving d4T, 3TC and indinavir for at least one year since PHI were included in an STI protocol (2 months off therapy and 2—4 months on therapy +/- IL-2 [125,000 units /m²/day] after the first cycle off therapy). PVL, genotypic resistance, CD4⁺/ CD8⁺T cells, CD4⁺lymphocyte proliferative responses (LPR) to HIV-1 proteins and HIV-1-specific CTL responses were assessed weekly after each discontinuation and monthly after reintroduction of HAART. Tonsillar biopsy and TRECs were made before STI.

Results:7 patients completed the first cycle off therapy. 6 were homosexual men and one was a heterosexual female. Median (range) age was 35 years (24—43 years). Median (range) PVL at PHI was 127,000 copies/mL (21,350—>1,000,000). No genotypic resistance to antiretrovirals was found. After a median (range) of 24 months (12—28 months) of HAART, all patients had plasma PVL <5 copies/mL and none of them had HIV-specific CD4⁺LPR. A rebound in PVL (>200 copies/mL) was detected in all patients after 2 weeks off therapy, with a median (range) peak of 37,000 copies/mL (18,000-272,000 copies/mL). HIV-1 specific CD4⁺LPR was detected in 5 patients (71%), and in 3 of them this response was coupled with a spontaneous PVL drop (>1 log₁₀/mL), which was <200 copies/mL in 2 cases. PVL also dropped in one out of two cases without HIV-1-specific CD4⁺LPR.

Conclusions:These preliminary data show that HIV-1-specific CD4⁺LPR response can be detected after the first STI cycle in most patients receiving HAART within 90 days after PHI and that this response is associated with a spontaneous reduction of HIV-1 viremia. HIV-1-specific CTL response will be presented.