Cervicovaginal HIV-1-neutralizing immunoglobulin A detected among HIV-1-exposed seronegative female partners in HIV-1-discordant couples

Abstract

Objective: Cervicovaginal HIV-1-neutralizing immunoglobulin A (IgA) was associated with reduced HIV-1 acquisition in a cohort of commercial sex workers. We aimed to define the prevalence and correlates of HIV-1-neutralizing IgA from HIV-1-exposed seronegative (HESN) women in HIV-1-serodiscordant relationships.

Methods: HIV-1-serodiscordant couples in Nairobi were enrolled and followed quarterly up to 2 years, and women in concordant HIV-1-negative relationships were enrolled as controls. Cervicovaginal, seminal, and blood samples were collected at enrollment and follow-up. Cervicovaginal IgA was assessed for HIV-1-neutralizing activity by a peripheral blood mononuclear cell-based assay using an HIV-1 clade A primary isolate.

Results: HESN women in discordant relationships had significantly more HIV-1-neutralizing IgA detected in genital secretions compared with control women [36 of 155 (23%) vs. four of 70 (6%), respectively; odds ratio (OR) 5.0; 95% confidence interval (CI) 1.70-14.64; P = 0.003]. These responses persisted over time in all available follow-up cervicovaginal samples from women with detectable HIV-1-neutralizing IgA at baseline. Partner median HIV-1 plasma viral load was lower among women who had HIV-1-neutralizing IgA compared with women without detectable activity (4.3 vs. 4.8 log(10) copies/ml, respectively; OR 0.70; 95% CI 0.51-0.94; P = 0.02). A similar trend was found with partner seminal viral load (OR 0.57; 95% CI 0.32-1.02; P = 0.06).

Conclusion: HESN women were five times more likely to have neutralizing IgA in cervicovaginal secretions than low-risk control women, and these responses were inversely associated with partner viral load. These observations support the existence of antiviral activity in the mucosal IgA fraction following sexual HIV-1 exposure.

Figure 1. Presence of cervicovaginal HIV-1 neutralizing IgA in HIV-1 exposed seronegative (HESN) and control women

Cervicovaginal samples were collected from HESN and control women. Thirty-six (23%) of 155 HESN women and 4 (6%) of 70 control women had neutralizing activity (P=0.003). After excluding samples with detectable prostate specific antigen (≥1µg/ml), this association remained significant (P=0.01)

Figure 2. Plasma and seminal HIV-1 viral load in male partners of HIV-1 exposed seronegative (HESN) women with and without detectable cervicovaginal HIV-1-neutralizing IgA

A comparison was made for (a) plasma and (b) seminal HIV-1 viral loads in male partners among HESN women with and without detection of cervicovaginal HIV-1-neutralizing IgA. Plasma and seminal viral loads below the lower limit of detection were set to half the lower limit (75 copies/mL for plasma and 250 copies/mL for semen), as indicated by the broken line. Solid lines indicate median concentration, whiskers indicate 5–95 percentile. P-values for plasma and seminal viral loads comparisons were 0.02 and 0.06, respectively.