The antiretroviral drugs AZT (zidovudine, Retrovir), 3TC (lamivudine, Epivir) and FTC (emtricitabine, Emtriva) rapidly achieve high concentrations in the female genital tract, according to a study presented to the Thirteenth Conference on Retroviruses and Opportunistic Infections in Denver on February 8th. The investigators, from the University of North Carolina, suggest that their findings show that these drugs would be “excellent candidates for pre-exposure prophylaxis (PREP) and post-exposure prophylaxis (PEP) regimens.”
Antiretroviral drugs have been shown to reduce HIV viral load in the genital tract, which could potentially decrease the risk of sexual transmission of HIV. Specific anti-HIV drugs which rapidly achieve high concentrations in the genital tract would make particularly useful candidates for PREP or PEP treatment regimens.
In order to determine which drugs could have the potential to be used most successfully in this way, the North Carolina investigators conducted an open label study looking at first dose and steady state concentrations of ten antiretroviral drugs in the genital tract of 23 HIV-positive women.
The women were treated with antiretroviral regimens that included 3TC, AZT, abacavir (Ziagen), ddI (didanosine, Videx), d4T (stavudine, Zerit), efavirenz (Sustiva), lopinavir/ritonavir (Kaletra) and atazanavir (Reyataz).
Paired blood plasma and genital tract samples were obtained on day one and day 21 to determine rapid and steady state concentrations of the individual drugs.
On both day one and day 21, concentrations of AZT, 3TC and FTC were higher in the genital tract than in the blood plasma (p < 0.02). There was a trend for genital tract concentrations of abacavir and ddI to be higher than blood plasma concentrations on day one, but not day 21. Concentrations of d4T, ritonavir, efavirenz, Kaletra and atazanavir were lower in the genital tract than in the blood on both day one and day 21 (p < 0.03).
“Understanding the exposure profiles of antiretrovirals in the genital tract is particularly important for PREP and PEP and possibly the prevention of mother-to-child transmission”, comment the investigators. “AZT, 3TC and FTC achieve genital tract exposures greater than that in blood plasma” and as it is known that plasma concentrations of these drugs is sufficient to effectively suppress HIV, “it would be expected that the higher genital tract concentrations would make these excellent candidates for PREP/PEP regimens.”
Dumond J et al. First dose and steady-state genital tract pharmacokinetics of ten antiretroviral drugs in HIV-infected women: implications for pre- and post-exposure prophylaxis. Thirteenth Conference on Retroviruses and Opportunistic Infections, Denver, abstract 129, 2006.