Female genital tract shedding of HIV-1 is rare in women with suppressed HIV-1 in plasma

Abstract

Objective: Determine the frequency of genital HIV-1 shedding in a large cohort of women on long-term suppressive antiretroviral therapy (ART) and its association with mucosal inflammation.

Design: We measured levels of HIV-1 RNA and inflammation biomarkers in cervicovaginal lavage (CVL) from HIV-seropositive women enrolled in the Women's Interagency HIV Study (WIHS).

Methods: HIV-1 was quantified (Abbott RealTime HIV-1 assay) from CVL samples of 332 WIHS participants with and without clinical evidence of genital inflammation at the time of CVL collection; participants had suppressed plasma viral load (PVL; limit of quantitation less than 20-4000 copies/ml depending on year of collection) for a median of 7.1 years [interquartile range (IQR) 3.4-9.8, Group 1] or for a median of 1.0 years (IQR = 0.5-1.0, Group 2). Twenty-two biomarkers of inflammation were measured in CVL to compare with clinical markers.

Results: HIV-1 was detected in 47% of 38 pre-ART CVL samples (median 668 copies/ml) and detection in CVL was associated with higher pre-ART PVL. HIV-1 was detected in only 1 of 38 CVL samples from these women on suppressive antiretroviral therapy for 1 year. No HIV-1 RNA was detected in 294 CVL samples from a cross-sectional set of women with suppressed PVL for a median of 7 years. Clinical inflammation markers were correlated with inflammatory biomarkers in CVL specimens, although genital inflammation was not associated with measurable genital HIV-1 shedding in these WIHS participants on ART.

Conclusion: ART that suppresses HIV-1 in the plasma of women also prevents genital tract HIV-1 shedding, even in the presence of genital tract inflammation.

Figure 1.. HIV-1 RNA levels in plasma and CVL from 37 WIHS participants before ART initiation.

CVL with detectable viral loads are shown in gray circles and CVL with undetectable viral loads are shown in white circles.

Figure 2.. Immune biomarker associations with number of clinical inflammation markers at pre-ART initiation and post-virologic suppression visits of WIHS participants.

Kendall tau-b values plotted for pre-ART (n=37) and post-suppression (n=38) for each of the 21 biomarkers (GM-CSF, IFN-γ, IL-10, IL-12p40, IL-12p70, IL-15, IL-1RA, IL-1α, IL-2, IL-4, IL-6, IL-8, IP10, MCP-1, MIP-1β, RANTES, TNFα, CD163, SLPI, IFN-α, beta-defensin 2 (BD2) and beta-defensin 3 (BD3)). Clinical inflammation markers included vaginal pH>5.5, visible cervical lesions, cervical ectopy, cervical friability, cervical exudate, trichomoniasis, and inflammation noted on Pap smear.