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Darunavir Penetrates Semen Well With High Levels Through 24 Hours
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17th Conference on Retroviruses and Opportunistic Infections, February 16-19, 2010, San Francisco
Mark Mascolini
Darunavir concentrations in semen consistently exceeded the 50% effective concentration (EC50) for wild-type (nonmutant) virus for 24 hour after once-daily dosing, according to a 34-sample analysis involving 18 HIV-infected men [1]. All blood samples and one third of seminal samples throughout the dosing interval had enough darunavir to exceed the EC50 required to inhibit darunavir-resistant HIV.
Stephen Taylor and colleagues in Birmingham and Liverpool measured time-matched blood and seminal samples from men taking 800 mg of darunavir once daily with 100 mg of ritonavir, plus other antiretrovirals. The 18 study participants produced 34 closely timed samples, and 5 men gave four or more matched samples at designated points after darunavir dosing (0, 2, 4, 6, and 24 hours). Everyone was taking darunavir for at least 2 weeks. Their CD4 counts ranged from 87 to 850.
With an assay that detects 200 copies/mL, the investigators saw HIV RNA in a semen sample of only one man. He had a seminal viral load of 1460 copies, and his seminal load remained detectable on two later samples produced 6 days apart. This man declined testing for sexually transmitted infections, which can affect viral load. Because Taylor could not detect HIV RNA in blood samples from this man, he cautioned that undetectable virus in blood does not invariably signal undetectable virus in semen.
Published EC50s for darunavir are 55 ng/mL for wild-type virus and 550 ng/mL for resistant virus. The assay used in this study had a lower detection limit of 79 ng/mL. Median (and interquartile range) darunavir concentrations waned slowly but steadily over the three dosing intervals:
· 1 to 3 hours: 5579 ng/mL (4639 to 7505) in blood, 588 ng/mL (509 to 778) in semen
· 4 to 6 hours: 3734 ng/mL (2935 to 4586) in blood, 490 ng/mL (479 to 640) in semen
· 22 to 24 hours: 2445 ng/mL (1365 to 3167) in blood, 217 ng/mL (172 to 261) in semen
Median semen-to-blood ratios stayed steady in the hours after dosing: 0.11 (0.09 to 0.15) at 1 to 3 hours (n = 8), 0.13 (0.07 to 0.18) at 4 to 6 hours (n = 13), and 0.11 (0.09 to 0.15) at 22 to 24 hours (n = 14).
All darunavir concentrations in blood and semen remained above the EC50 for wild-type virus at every point. All blood concentrations stayed above the EC50 for resistant virus, as did one third of seminal darunavir levels.
Taylor and colleagues believe their findings suggest darunavir "has good penetration into the semen of HIV-1 infected men with concentrations approximating 10-20% of the concentration achieved in the blood plasma" throughout a 24-hour dosing interval.
Reference
1. Taylor S, Jayasuriya A, Dufty N, et al. Darunavir concentrations exceed the protein-corrected EC50 for wild type HIV in the semen of HIV-1-infected men. 17th Conference on Retroviruses and Opportunistic Infections. February 16-19, 2010. San Francisco. Abstract 611. http://www.retroconference.org/2010/PDFs/611.pdf.
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