408   Hydroxyurea Suppresses Formation of HIV-p24-Specific T- cells When Administered During Acute HIV Infection.

J. Demarest*¹, M. Kelly¹, J. Ottinger¹, V. Edmundson¹, J. Mathieson¹, H. Staats¹, S. Fiscus², C. D. Pilcher², J. Lennox³, J. J. Eron, Jr.², and C. B. Hicks¹.
¹Duke Univ. Med. Ctr., Durham, NC,²Univ. of North Carolina, Chapel Hill; and³Emory Univ., Atlanta, GA.

Background:Administration of protease inhibitor (PI)-containing combination anti-retroviral therapy (ART) during primary HIV-1 infection (PHI) has been shown to preserve certain HIV-specific immune responses and may impact clinical course of disease. We examined the impact of a non-PI ART including d4T, ddI, NVP, and hydroxyurea (HU) given during PHI on several immune parameters in 13 subjects over 56—68 weeks of therapy; one additional subject did not receive HU.

Methods:Longitudinal analysis of T-cell phenotype and lymphocyte proliferative responses to recall and HIV antigens.

Results:Coincident with a marked reduction of plasma HIV-1 RNA, we found favorable changes in the absolute number of memory, naïve, and activated T-cells over the first 24 weeks (delta memory: CD8 = -272/ml, CD4 = +72/ml; delta naïve: CD8 = +29/ml, CD4 = +83/ml). Following discontinuation of HU in most individuals by weeks 16—24, a more significant rise in T-cell subsets could be appreciated (delta Wk56: CD4 = +283/ml; CD8 = -425/ml). In addition, a modest increase in the proportion of activated T-cells was found (CD38⁺HLA-DR⁺: Wk24 — CD4 = 3.4%, CD8 = 15.6%; Wk56: CD4 = 5.3%, CD8 = 21.5%). Minimal to undetectable HIV-1-p24- specific proliferative responses were present in those subjects receiving HU, whereas strong reactivity was readily detectable in one subject not receiving HU (SI: Wk0 = 36, Wk29 = 466). Following cessation of HU, the majority of individuals exhibited significant HIV-p24-specific proliferative responses. The response to CASTA, a recall antigen, did not appear to be significantly impacted during time on HU.

Conclusions:The data suggest that HU-containing ART initiated during PHI may suppress the magnitude of change in T-cell subsets and the response to a neo- (HIV) but not recall (CASTA)antigen. Upon stopping HU, more robust increases in T-cell subsets and CD4 responses to HIV could be appreciated. The ultimate impact on clinical outcome remains to be determined.