Standard HIV treatment achieves high concentrations in female genital tract and suppresses shedding of virus

Standard antiretroviral therapy containing tenofovir, FTC and atazanavir achieves high concentrations in the female genital tract and suppresses HIV replication throughout the menstrual cycle, US investigators report in the online edition of the Journal of Infectious Diseases.

“We demonstrate that in a population of women on long-term ART [antiretroviral therapy] with a commonly prescribed first-line regimen, genital concentrations exceeded plasma concentrations for all active drugs in the regimen and resulted in suppression of genital HIV-RNA shedding,” comment the authors. “Genital tract HIV-1 RNA shedding was uncommon even…during the menstrual cycle.”

They believe their findings lend further support to the use of HIV treatment as prevention.

Antiretroviral therapy suppressed viral load in blood and genital secretions. The aim of treatment is undetectable blood plasma viral load, which is associated with an extremely low risk of HIV transmission to sexual partners.

Levels of viral load in plasma and genital secretions are highly correlated, but some research has shown that women can have intermittent shedding of HIV in the genital tract even in the presence of fully suppressed plasma viral load. The reasons for this and its significance in terms of the risk of onward HIV transmission are uncertain.

However, it is known that antiretroviral concentrations in the female genital tract can vary between drugs. 

Because of this, investigators wanted to see if variations in the concentrations of commonly used anti-HIV drugs were associated with genital tract shedding of HIV through the menstrual cycle.

They therefore designed a study involving 20 adult, non-pregnant, pre-menopausal women taking ritonavir-boosted atazanavir (Reyataz) with FTC/tenofovir (Truvada).

All had an undetectable plasma load for at least 90 days. The median duration of antiretroviral treatment was 90 months, and the women had been taking atazanavir/ritonavir and Truvada  for a median of 14 months.

Blood and cervico-vaginal samples were collected twice weekly for three weeks and tested for antiretroviral drug concentrations, HIV-1 RNA (viral load) and HIV DNA.

Genital concentrations exceeded those in plasma for each of the three drugs. Concentration ratios were highest for FTC (11.9; 95% CI, 8.66-16.3), followed by tenofovir (3.52; 95% CI, 2.27-5.48) and atazanavir (2.39; 95% CI, 1.69-3.38). This pattern was observed throughout the menstrual cycle.

HIV-1 RNA was detected in 69 plasma samples (59%) from 16 women (80%). However, in only 13 samples was viral load measureable (50-395 copies/ml). As expected, HIV DNA was present for all patients at all visits.

Genital tract HIV-1 RNA was detected in 19 samples (16%) from nine women (45%). All samples were below 50 copies/ml. Genital shedding of HIV was detected in three women on one occasion, in four women on two occasions and in two women more than twice.

HIV DNA was detected in the 42 genital samples (36%) from 14 women (70%). In 14 samples (74%) HIV-1 RNA was also shed.

A mucosal leukocyte count above 200 cells/μl was associated with detection of both genital HIV-1 RNA (rate ratio = 2.38; 95% CI, 1.03-5.51) and DNA (rate ratio = 2.41; 95% CI, 1.52-3.80). There was no association with genital shedding of HIV and genital antiretroviral concentrations, menstrual cycle phase, bacterial vaginosis, genital bleeding or detection of HIV-1 RNA in plasma.

“Our study provides evidence that high mucosal antiretroviral concentrations generally suppress local viral replication throughout the menstrual cycle in women on ART,” conclude the authors. “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.”