Antiretroviral drug exposure in the female genital tract

Polly Clayden, HIV i-Base

A paper in the September 2007 edition of AIDS reported data from a study to evaluate antiretroviral exposure in the genital tract of HIV-positive women. Julie Dumond and coworkers from the School of Pharmacy, University of North Carolina looked at 11 commonly used antiretroviral medications in the three drug classes: nucleoside/tide analogue reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI), and protease inhibitors (PI).

The investigators hypothesised “to prevent sexual transmission of HIV in women, oral antiretroviral drugs that achieve high concentrations quickly in the genital tract after a first dose would be optimal candidates for PEP or PrEP regimens.” The study was undertaken as no human pharmacology data have been generated in either healthy volunteers or HIV-positive women “that allow rational selection of drugs used for this purpose.”

The study objective was to describe first dose and steady state antiretroviral exposure in the female genital tract and exposure in cervicovaginal fluid relative to blood plasma. It was a non- blinded, open label study of 27 women initiating combination therapy at a single centre from November 2002 to May 2006.

The women in the study were mainly African American (70%) with a median age of 35 (IQR 31-42) years, CD4 count of 307 (IQR 220-372) cells/mm3 and viral load of 4.7 (IQR 4.0-5.0) log10 copies/mL at entry. 67% of the women were drug experienced.

For both first dose and steady state (at least three weeks after first dose) concentration samples were taken at 0 (predose), 2, 4, 6, 12 and 24 hours after observed doses. The drugs were ranked according to the genital tract concentrations achieved relative to blood plasma. The investigators found the median rank order of highest to lowest genital tract concentrations relative to blood plasma at steady state were: 3TC (concentrations were 411% greater than blood plasma), FTC (395%), AZT (235%) tenofovir (75%), ritonavir (26%), ddI (21%), atazanavir (18%), lopinavir (8%), abacavir (8%), d4T (5%), and efavirenz (0.4%).

They wrote: “The results of this investigation support the use of 3TC, ZDV and TDF, and potentially FTC as excellent preexposure/ post-exposure prophylaxis (PrEP/PEP) candidates. ATZ and LPV/r might be useful agents due to favourable genital tract concentrations in relation to HIV-1 wild-type susceptibility. We believe that agents that achieve less than 10% of blood plasma exposure, such as efavirenz and d4t, are less likely PrEP/PEP candidates.”


For rational selection of PEP and PrEP agents, we must have a thorough understanding of the pharmacology of these drugs at the site of infection. This study was a first step in that direction.


Dumond JB, Rosa, Yeh RF, Pattersonc KB et al. Antiretroviral drug exposure in the female genital tract: implications for oral pre- and postexposure prophylaxis. AIDS 2007, 21:1899–1907.

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