Orally exposed uninfected individuals have systemic anti-HIV responses

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

The aim of this study was 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. Plasma samples were collected from exposed uninfected individuals (n = 25), HIV-positive 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-1-exposure, and clinical records documented viral loads in HIV-positive partners. At enrolment, plasma samples from seven of 25 exposed 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 plasma immunoglobulin (Ig) A1-mediated neutralization was observed in six of the seven 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. 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.

Editors’ note: In this intriguing study of discordant couples of men who have sex with men, oral mucosal exposure to HIV (measured as the highest observed level of HIV-RNA in each subject’s infected partner) was correlated with the development of a functional anti-HIV response in the plasma. Looking for explanations, the researchers checked for the CCR5 delta 32 deletion that confers protection if both genes are affected but only one individual was homoyzygous. One of the seven men that had anti-HIV responses subsequently became infected, but with a different clade than the one his partner had. This suggests that the antibodies that were generated, if protective, are not likely to be broadly neutralizing. In any case, the findings of this study have implications for vaccine research because they suggest that low-level mucosal exposure may induce acquired immunity.