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ART suppresses genital virus shedding throughout menstrual cycle
New data suggest that antiretroviral therapy suppresses genital shedding of the virus during the menstrual cycle even when other risk factors for genital HIV shedding are present.
“Our study demonstrated near complete suppression of genital HIV-1 RNA shedding through the menstrual cycle in the presence of highly variable genital concentrations,” researchers from Emory University wrote in The Journal of Infectious Diseases. “Although the significance of low-level genital HIV-1 RNA and HIV-1 DNA remains unclear, our study provides evidence that high mucosal antiretroviral concentrations generally suppress local viral replication throughout the menstrual cycle in women on ART.”
The study included 20 women with HIV who were on ART and had suppressed plasma viral loads. The median length of diagnosis was 9 years and all women had received any ART for a median of 90 months and had received their current ART for a median of 14 months. The researchers collected blood and cervicovaginal samples twice weekly for 3 weeks to test for ART concentrations, HIV-1 RNA and proviral DNA.
Among the women, 17 had sexual activity within the past 6 months, one used hormonal contraception, all were negative for gonorrhea and chlamydia, two were positive for syphilis and 19 were positive for herpes simplex virus 2 immunoglobulin G. In addition, five women had asymptomatic Candida infection or bacterial vaginosis, five reported dysplasia on their most recent Pap test and six had received treatment for a vaginal infection within the past 30 days.
The genital concentrations of the ART drugs exceed plasma concentrations for all drugs. The geometric mean ratio of genital to plasma concentration was 11.9 (95% CI, 8.66-16.3) for emtricitabine (Emtriva, Gilead), 3.52 (95% CI, 2.27-5.48) for tenofovir (Viread, Gilead) and 2.39 (95% CI, 1.69-3.38) for atazanavir (Reyataz, Bristol-Myers Squibb) boosted with ritonavir (Norvir, AbbVie).
HIV-1 RNA (<50 copies/mL) was detected in 19 cervicovaginal lavage samples from nine women. Seven of these occurred when there was no detectable RNA in the plasma and nine when the plasma RNA was <50 copies/mL. HIV-1 DNA was detected in 42 cervicovaginal lavage samples from 14 women. DNA was detected in 14 of the visits where RNA was detected in the samples.
The researchers did not find any pattern of plasma or genital drug concentration related to shedding. Semen contamination, bacterial vaginosis and plasma RNA were not associated with genital RNA or DNA detection.
“Given the direct relationship between cervicovaginal HIV-1 RNA levels and female-to-male sexual transmission, our findings lend support for ART as a tool for the prevention of sexual transmission of HIV,” the researchers wrote.
Disclosure: The researchers report no relevant financial disclosures.