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332 Comparison of HIV-Specific Immunity in HIV Exposed Uninfected Individuals (EUs) Who Remain Seronegative with That in EUs Who Eventually Seroconvert
G. Makedonas*1, A. Merchant1, J. Bruneau2, F. Lamotthe2, R. Sekaly3, and N. Bernard1
1McGill Univ., Montreal, Canada; 2CHUM, Montreal, Canada; and 3Univ. de Montreal, Canada
Background: Some individuals, despite numerous exposures to HIV, remain seronegative. Studying (EUs) is important because EUs may hold the key to what constitutes acquired protective immunity to HIV, the goal for an effective HIV vaccine. If the development of an immune response to HIV in EUs plays a role in preventing progressive HIV infection, then one would expect a higher proportion of EUs who remain seronegative than those who seroconvert to possess HIV-specific effector activity.
Methods: Group I is composed of 14 intravenous drug users (IVDU) who remain seronegative despite exposure to HIV through admitted needle sharing with partner(s) known to be HIV infected. Group II consists of 6 IVDUs who seroconverted after similar exposure to HIV. Peripheral blood mononuclear cells (PBMC) from Group II were obtained from time points within 6 months prior to seroconversion. The ELIspot assay was used to measure the frequency of HIV-specific IFN-gamma-secreting cells. PBMC were stimulated with a panel of synthetic HIV peptides in an MHC class I-restricted fashion. A response was deemed positive if the average number of spots in the test wells was 2-fold over that in the no peptide-stimulated control wells. The samples were assayed in a blinded manner.
Results: None of the 6 EUs who seroconverted had evidence of HIV-specific effector activity at the time points tested 6 months prior to seroconversion, whereas 10 of 14 (71.4%) Group I subjects exhibited HIV-specific effector activity, as defined by responding to at least 1 HIV peptide (p = 0.0025; Fisher’s exact test).
Conclusions: These results confirm previous data generated by us and others that demonstrate that exposure to HIV can result in induction of HIV-specific effector activity without seroconversion and establishment of progressive infection. These results are consistent with the hypothesis that an association exists between HIV-specific effector activity in EUs and maintenance of seronegativity.
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