Orally exposed uninfected individuals have systemic anti-HIV responses associating with partners' viral load.

Objectives: To determine whether oral HIV-1 exposure incites a persistent systemic anti-HIV-1 response in exposed uninfected individuals of discordant couples of men who have sex with men, and whether this response associates with HIV-1 exposure measured by viral load in the HIV-positive partners. Methods: Plasma were collected from exposed uninfected individuals (n! 25), HIVpositive partners (n! 25) and low-risk controls (n! 22). A peripheral blood mononuclear cells-based neutralization assay was used to test these samples against three primary HIV-1 isolates. Self-reported questionnaires described routes of HIV-1exposure, and clinical records documented viral loads in HIV-positive partners. Results: At enrolment,plasma samplesfrom sevenof25exposed uninfected individuals neutralized at least two of the three HIV-1 isolates. No samples from the 22 controls neutralized any HIV-1 isolate (P! 0.01). Of these seven exposed uninfected individuals, six retained neutralization capacity during follow-up. Neutralization capacity among exposed uninfected individuals associated with the highest measured viral load of their respective partners (P! 0.01) and also time since highest viral load (P! 0.02). Purified plasmaimmunoglobulin(Ig)A1-mediatedneutralizationwasobservedinsixoftheseven samples, whereas none of the IgA1-depleted plasma samples neutralized HIV-1. The neutralizing IgA1 was not HIV envelope specific as detected by ELISA and western blot. Conclusion: Orally exposed uninfected men who have sex with men can mount neutralizing anti HIV-1 activity in plasma, mediated primarily by non-HIV envelope-specific IgA1. Neutralization was associated with previous measured highest viral load in the HIV-positive partner, as well as time elapsed since the peak viral load. Neutralization also persisted over time in spite of a continuous low viral exposure. ! 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins AIDS 2010, 24:35‐43