Genital Shedding of HIV — The Effects of Antiretroviral Therapy and the Menstrual Cycle

Charles B. Hicks, MD reviewing Sheth AN et al. J Infect Dis 2014 Mar 18.

Cervicovaginal HIV RNA and proviral DNA were largely undetectable in women on atazanavir-based antiretroviral therapy.

 

Distribution of antiretroviral drugs into various compartments, including the female genital tract, is not well characterized. Concern has been raised about the possibility of intermittent viral shedding, particularly in the presence of factors known to increase it (sexually transmitted infections, bacterial vaginosis, local inflammation, and menstrual-cycle phase).

To address these concerns, investigators studied 20 HIV-infected women with normal menstrual cycles who were taking TDF/emtricitabine/ritonavir-boosted atazanavir and had documented undetectable plasma HIV RNA. Blood and cervicovaginal (CV) samples were collected twice weekly for 3 weeks and tested for antiretroviral-drug concentrations, HIV RNA, and proviral DNA. If a study visit coincided with menses, sample collection was delayed until after the end of menstruation.

Despite considerable within- and between-person variability, concentrations of all three antiretroviral drugs were higher in CV samples than in concomitant plasma specimens, with CV/plasma ratios of 11.9 for emtricitabine, 3.52 for TDF, and 2.39 for atazanavir. HIV RNA was detected at low levels (<50 copies/mL) in CV samples of 9 women (45%; 16% of all sampling events), and proviral DNA was found in CV samples of 14 (70%; 36% of sampling events). Detection of HIV RNA or proviral DNA in CV samples was not associated with genital antiretroviral-drug concentrations, menstrual-cycle phase, bacterial vaginosis, genital bleeding, or detection of HIV in plasma but was associated with CV inflammation (as evidenced by higher levels of CV leukocytes).

COMMENT

These results provide pharmacological support for the findings of the HPTN 052 study, which suggested that standard dosing of antiretrovirals diminishes HIV transmission. The conclusions must be considered cautiously, given the relatively small sample size and the fact that only two symptomatic vaginal infections were diagnosed during the study. Nonetheless, the data strongly support the benefits of suppressive antiretroviral therapy in reducing sexual transmission of HIV, even in the presence of other factors associated with increased HIV shedding.

Note to readers: At the time NEJM Journal Watch reviewed this paper, its publisher noted that it was not in final form and that subsequent changes might be made.

CITATION(S):

  1. Sheth AN et al. HIV-1 genital shedding is suppressed in the setting of high genital antiretroviral drug concentrations throughout the menstrual cycle. J Infect Dis 2014 Mar 18; [e-pub ahead of print]. (http://dx.doi.org/10.1093/infdis/jiu166)