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


RESULTS
At enrollment, 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.


CONCLUSIONS
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.
Hasselrot
Klara
K
Department of Medicine, Infectious Disease Unit, Center for Molecular Medicine(CMM), L8:01, Karolinska University Hospital, Solna, S-17176 Stockholm, Sweden. klara.hasselrot@ki.se
Bratt
Göran
G
Hirbod
Taha
T
Säberg
Pär
P
Ehnlund
Mariethe
M
Lopalco
Lucia
L
Sandström
Eric
E
Broliden
Kristina
K
D000328:Adult; D057134:Antibodies, Neutralizing / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D015483:HIV Antibodies / Q000096:biosynthesis / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D018023:HIV Seronegativity / Q000276:immunology; D006679:HIV Seropositivity / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D018451:Homosexuality, Male; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology; D007070:Immunoglobulin A / Q000276:immunology*; D008297:Male; D009061:Mouth Mucosa / Q000276:immunology / Q000821:virology; D012747:Sexual Partners; D011795:Surveys and Questionnaires; D019562:Viral Load / Q000276:immunology*
D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D007070:Immunoglobulin A