Induction of Systemic HIV-1-specific Cellular Immune Responses by Oral Exposure in the Uninfected Partner of Discordant Couples

Objectives: Previous studies have identified HIV-specific T-cell responses in HIV-exposed uninfected individuals (EUI). However, so far no study has investigated exposure through oral sex. Our aim was to investigate whether oral exposure is enough to induce a systemic HIV-specific T-cell response.

Design: Peripheral blood mononuclear cells were collected from 25 EUI living with a HIV-positive partner. Sexual behavior was described by the EUI in self-reported questionnaires. All clinical data of the infected partners were well documented.

Methods: Peripheral blood mononuclear cells were stimulated with five different HIV peptide pools and HIV-specific T-cell responses were detected using the interferon-[gamma] enzyme-linked immunospot assay. Multiple cytokine production was studied longitudinally using flow cytometry intracellular cytokine assay.

Results: The majority of the discordant couples reported having protected anal intercourse but unprotected oral sex. Three of the 23 tested EUI with evaluable results had HIV-Gag or Nef-specific T-cell responses. Two of the responders reported unprotected oral sex as the only route of exposure. The HIV-specific CD4+ and CD8+ T cells in the Gag-responder showed production of multiple cytokines. The magnitude of the responses decreased over time when the level of exposure, determined by the viral load in the partner, declined.

Conclusion: HIV exposure through oral sex is sufficient to induce systemic HIV-specific CD4+ and CD8+ T-cell immune responses in some uninfected individuals. Further investigation is needed to determine whether these responses have any protective role against HIV infection, or are merely evidence of exposure.