Background:  Data on female genital tract diffusion of protease inhibitors (PI) during pregnancy are scarce, despite the potential role of the HIV presence in vaginal secretions in vertical transmission. Our objective was to evaluate the penetration of different PI in genital tract of HIV-infected pregnant women.

Methods:  Paired plasma and cervico-vaginal concentrations of atazanavir (ATV), amprenavir (APV), indinavir (IDV), lopinavir (LPV), nelfinavir (NFV), and saquinavir (SQV) were determined using high performance liquid chromatography (HPLC) coupled with photodiode array-ultraviolet (PDA-UV) detection. Genital fluids were collected using cervico-vaginal lavage and blotting paper from the posterior fornix and endocervical canal in HIV-1-infected pregnant women. Plasma HIV RNA (pVL) and CD4 cell count were determined at the time of pharmacokinetic sampling. Median (IQR 25 to 75) was presented.

Results:  We enrolled in this pilot study, 20 HIV-1-infected pregnant women (aged 33 years, 30 to 35) (25 weeks of gestation; 22 to 30), treated with a PI-containing regimen. In 18 of 20 patients, plasma viral loads were <200 copies/mL; 2 patients had detectable plasma viral loads, 1 for non-compliance and 1 in the early phase of plasma viral loads decrease. CD4 count was 349/µL (264 to 552). Plasma concentrations were 744 ng/mL (n = 8) for ATV, 808 ng/mL (n = 2) for IDV, 4548 ng/mL (n = 5) for LPV, 2964 ng/mL (n = 2) for APV, 988 ng/mL (n = 1) for SQV, and 3870 ng/mL (n = 1) for NFV. Similar results were obtained between cervico-vaginal lavage and blotting paper from the posterior fornix and endocervical canal regarding PI diffusion. LPV and SQV demonstrated no diffusion in vaginal fluids (<300 and <200 ng/mL, respectively); the cervicovaginal/plasma concentration ratios for ATV, IDV, APV, and NFV were 84%, 371%, 30%, and 72%, respectively.

Conclusions:  In this pilot study, cervico-vaginal lavage and blotting paper allowed to collect cervicovaginal fluids with consistent results. Major differences in cervico-vaginal diffusion between PI were found, which may be related to characteristics of these drugs (protein binding, lipo-solubility).