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Session 45 Poster Session Exposed Uninfected Individuals Session Time: 4:30-6:30 pm Room 4E-F

262-T. Immune Correlates of Protection in HIV-Exposed but Uninfected Heterosexual Males S. Lo Caputo*1, D. Trabattoni2, F. Vichi1, M. L. Fusi2, G. Maffeis2, D. Luzzeri2, S. Fossati2, L. Lopalco3, F. Mazzotta2, and M. Clerici1 1Hosp. SM Annunziata, Firenze; 2Univ. of Milano; and 3DIBIT, Milano, Italy Background: Exposure to HIV in the absence of infection is now well documented. Data are missing on the mucosal immune correlates of this condition in exposed seronegative (ESN) male heterosexual partners of HIV-infected women. Methods: Analysis of PBMC, seminal fluid and seminal mononuclear cells, and urethral swabs were performed in 14 ESN males with repeated and recent (<4 months) sexual exposure to HIV (ESN), of 7 HIV-infected patients (HIV), and of 7 healthy controls. Humoral (IgG and IgA by ELISA) and cellular (FACS determinations and ELISPOT and intracellular cytokines in env, p17; p24 stimulated conditions) analyses were performed. Results: HIV-specific IgA were detected in semen and urethral swabs of ESN and HIV but not in HC (mean OD: ESN= 0.41; HIV= 0.50; HC= 0.008)(ESN vs HIV+ p= ns; ESN vs HC p= 0. 02). Neutralization of 2 HIV primary isolates was seen at high dilutions (1:270) with seminal fluid of ESN and HIV but was absent in HC. Seminal blood lymphocytes of ESN were enriched in activated populations including CD8+38+RO (mean%: ESN= 14. 8; HIV+= 35. 9; HC= 4. 5)(ESN vs HIV+ p= ns; ESN vs HC p= 0. 04) and CD4+25+(mean%: ESN= 17. 9; HIV+= 36. 1; HC= 5. 1)(ESN vs HIV+ p= ns; ESN vs HC p= 0. 07). Interestingly, an augmented percentage of activated T lymphocytes was not present in the peripheral blood of ESN. Robust env-, p17- and p24 specific CTL were detected (ELISPOT) in the peripheral blood of ESN (mean, background subtracted: env= 34; gag= 24; pol= 82 SFU/106 PBMC), CTL were weaker in HIV+ and absent in HC. Flu-specific CTL (control antigen) were comparable in ESN and HC but reduced in HIV+ patients. Env-, p17- and p24-specific IFN-gamma-producing CD4+ peripheral lymphocytes (intracellular FACS) were similarly strong in ESN, weak in HIV, and absent in HC. Conclusions: Exposure to HIV results in the activation of mucosal and systemic immune mechanisms in heterosexual males in whom infection cannot be detected by virological or clinical parameters. Immune activation in ESN males is compartimentalized; HIV-specific CD4 and CD8 T cells are nevertheless observed in the peripheral blood. These immune mechanisms should be reproduced in vaccine design.

©2002 9th Conference on Retroviruses and Opportunistic Infections