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Raltegravir Level at End of Dosing
Interval High in Male and Female Genital Tract
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52nd ICAAC, September 9-12, 2012, San Francisco
Mark Mascolini
Raltegravir concentrations at the end of a dosing interval in men and women were usually higher in the genital tract than in plasma and lay above the integrase inhibitor's 95% effective concentration (EC95) for all study participants [1].
If antiretrovirals do not penetrate the genital tract well, the tract can become a sanctuary site for ongoing viral replication. Ongoing replication in the genital tract could raise the chance of HIV transmission in people with an undetectable viral load in plasma. University of Rochester researchers conducted this study to see if raltegravir concentrations in the genital tract at the end of a dosing interval are high enough to control viral replication.
The study involved HIV-positive men and women who had taken the same standard-dose raltegravir-containing combination for at least 3 weeks. Women had to refrain from sexual intercourse, intravaginal medications, and douching for 72 hours before cervicovaginal sampling. After fasting 10 hours, study participants received an observed standard dose of raltegravir with a standardized breakfast at the study site. Plasma and genital tract samples were collected 8 to 10 hours after the observed dose. Women gave cervicovaginal samples within 14 days after the end of menses. Men provided ejaculate samples.
The study included 8 women and 8 men with average ages of 42 (+/- 8.0) in women and 52 (+/- 6.2) in men. Participants had taken raltegravir for a median of 465 days (range 106 to 1511), and median CD4 count stood at 756 (range 91 to 1760). Thirteen people (81%) had a viral load below 48 copies.
Median raltegravir plasma concentration was 199 ng/mL (interquartile range [IQR] 104.4 to 494.7). Median genital tract concentrations were 879.1 ng/mL (IQR 128.4 to 3541.4) in women and 485.1 ng/mL (IQR 428.5 to 753.3) in men. Median genital-to-plasma concentration ratios were 2.2 (IQR 0.6 to 5.6) in women and 4.3 (IQR 2.7 to 5.9) in men. Genital-to-plasma ratios were below 1.0 in 3 of 8 women and 1 of 8 men.
All study participants had a raltegravir genital tract concentration above the EC95 for HIV-variant H9IIIB (14.96 ng/mL). Genital tract concentrations did not differ significantly between women and men (P = 0.8) and genital-to-plasma ratios did not differ significantly between women and men (P = 0.4).
Because of the limited size of this analysis and large interpersonal variability, the Rochester team believes further study of raltegravir genital tract concentrations is warranted.
Reference
1. Dobson E, Luque A, Aslam F, DiCenzo R, et al. Comparing raltegravir genital tract distribution in HIV-infected men and women. 52nd Interscience Conference on Antimicrobials and Chemotherapy (ICAAC). September 9-12, 2012. San Francisco. Abstract A-1252.
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