Levels of etravirine (ETV) and ritonavir-boosted darunavir (DRV) were higher in rectal tissue than in plasma of 8 HIV-negative men taking the antiretrovirals for 8 days. Pharmacologically active levels of the two drugs were higher in semen than in plasma.

Antiretroviral therapy can lower the risk of HIV transmission by decreasing HIV RNA levels in blood, semen, and genital and rectal tissues. US researchers note that “defining the individual exposure of commercially available antiretroviral therapy in genital secretions and vulnerable mucosal tissues is paramount to designing future prevention interventions.”

The investigators measured darunavir, ritonavir, and etravirine levels in 12 HIV-negative men who took 600 mg of darunavir, 100 mg of ritonavir, and 200 mg of etravirine orally twice daily for 8 days. The researchers collected 7 blood plasma samples over 12 hours on day 1 (designated PK1) and on days 7 and 8 (PK2). They collected one rectal tissue sample during PK1 and PK2, 2 seminal plasma samples during PK1, and 6 seminal plasma samples over 2 days in PK2.

The 3 antiretrovirals could be detected in seminal plasma and rectal tissue within 1 hour after a single dose. In PK1 and PK2 seminal plasma exposures were lower than in blood plasma by 80% to 92% for darunavir, 89% to 95% for ritonavir, and 83% to 88% for etravirine. But because protein binding in seminal plasma compared with blood plasma was 14% lower for darunavir, 70% lower for ritonavir, and 97% lower for etravirine, pharmacologically active levels of the 3 antiretrovirals were higher in semen than in blood.

Compared with blood levels, antiretroviral concentrations in rectal tissue were 39- to 155-fold higher for darunavir, 12- to 61-fold higher for ritonavir, and 20- to 40-fold higher for etravirine.

The researchers propose that “the high protein-unbound exposures in seminal plasma and total exposures in rectal tissue support further investigations of darunavir plus ritonavir and etravirine in secondary prevention.”

They suggest that “high ritonavir concentrations may also be favorable for suppressing viral replication in the gastrointestinal mucosa.”

By Mark Mascolini

Source: Kevin C. Brown, Kristine B. Patterson, Steven H. Jennings, Stephanie A. Malone, Nicholas J. Shaheen, Heather M. Asher Prince, Melissa Spacek, Myron S. Cohen, Angela D.M. Kashuba. Single- and multiple-dose pharmacokinetics of darunavir plus ritonavir and etravirine in semen and rectal tissue of HIV-negative men. JAIDS. 2012; 61: 138-144.

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