Background:  Some women on effective ART with undetectable plasma viral load shed HIV in the genital tract. This discordance is not wholly explained by genital tract infections. We aim to determine the association between mucosal inflammation (as measured by genital tract white blood cells and genital tract shedding of HIV-1 RNA.

Methods:  The study enrolled women on effective ART with plasma viral load ≤80 copies/mL for at least 6 months. Serial paired plasma and genital tract HIV-1 RNA were measured every 4 weeks for 12 months. HIV-1 RNA was measured by nucleic acid sequence-based amplification assay. Genital tract secretions were collected by cervicovaginal lavage and Sno-Strips. Genital tract-white blood cells were measured by hemacytometry. Gonorrhea, Chlamydia, and syphilis were tested by urine nucleic acid amplification test and rapid plasma reagin at baseline. Bacterial vaginosis, Candida, and trichomoniasis were diagnosed by wet mount. HSV-2 DNA polymerase chain reaction (PCR) on cervicovaginal lavage was performed on women who were HSV-2 antibody positive. Generalized estimating equations with robust standard errors were used to estimate the prevalence and odds of detectable genital tract HIV-1 RNA when genital tract-white blood cells was present.

Results:  Over 12 months, 52 women contributed 364 visits. Median age was 44 years (range 31 to 63); 46% were black, 33% were white, and 15% were Hispanic; 19% (10 of 52) had had a hysterectomy; 52% (27 of 52) and 46% (24 of 52) were on a NNRTI and protease inhibitor (PI), respectively. Median CD4 was 465 cells/µL. Median genital tract-white blood cells was 10 cells/mm³ (range 0 to 4100); 36% (19 of 52) of women in 10% (30 of 364) of visits had detectable genital tract HIV-1 RNA. No gonorrhea, Chlamydia, or syphilis was detected, but 0.8% of visits exhibited trichomoniasis, 10% Candida, and 20% bacterial vaginosis. All women were HSV-2 antibody positive, and 7.1% had asymptomatic genital tract HSV-2 shedding, and 1.4% had symptomatic herpetic episodes. When visits with semen and diagnosed genital tract infections were excluded, genital tract-white blood cells was associated with genital tract HIV-1 RNA (OR 2.91, p = 0.012) after controlling for age, race, baseline CD4, and hysterectomy status. Genital tract-white blood cells remained associated with genital tract HIV-1 RNA when genital tract infections were included (OR 2.57, p = 0.008). None of the diagnosed genital tract infections was associated with genital tract HIV-1 RNA. Only Candida was found to be positively associated with presence of genital tract-white blood cells (p = 0.002). 

Conclusions:  In HIV-infected women on effective ART with undetectable plasma viral load, the prevalence of genital tract, HIV-1 RNA shedding is low. In this study, mucosal inflammation as measured by genital tract-white blood cells is associated with genital tract HIV-1 RNA shedding. Future studies need to explore the role of mucosal inflammation, mucosal immunology, and vaginal ecology in genital tract viral shedding.