Absence of HIV-1 shedding in male genital tract after 1 year of first-line lopinavir/ritonavir alone or in combination with zidovudine/lamivudine

作者：Ghosn Jade^*; Chaix Marie Laure; Peytavin Gilles; Bresson Jean Louis; Galimand Julie; Girard Pierre Marie; Raffi Francois; Cohen Codar Isabelle; Delfraissy Jean Francois; Rouzioux Christine

来源：Journal of Antimicrobial Chemotherapy, 2008, 61(6): 1344-1347.

DOI：10.1093/jac/dkn098

• protease inhibitor
• compartmentalization
• semen
• sanctuary site

Background: New strategies such as boosted-protease inhibitor (PI) monotherapy are being investigated. However, a concern remains regarding the efficacy of this strategy in viral sanctuaries such as the male genital tract. More than 80% of untreated HIV-infected men have detectable HIV-RNA in semen and such a strategy could favour local selection of resistant variants, given the poor penetration of most PIs in semen.
Objectives: To evaluate the impact of a first-line lopinavir/ritonavir alone or standard triple combination on HIV-1 shedding in the genital tract.
Methods: HIV-1-infected men enrolled in the Monark randomized trial were eligible for the present study after 48 weeks of a first-line lopinavir/ritonavir alone or in combination with zidovudine and lamivudine. Single-paired samples of blood and semen were collected at week 48. Blood plasma HIV-RNA and seminal plasma HIV-RNA were measured at week 48. Lopinavir and ritonavir concentrations were measured in blood and in semen at week 48 by high-performance liquid chromatography.
Results: Ten patients were included: five of them received lopinavir/ritonavir monotherapy and five received a triple combination. At week 48, all patients had blood plasma HIV-RNA < 1.7 log(10) copies/mL. Median lopinavir and ritonavir concentrations were within the expected therapeutic target range in blood plasma (4896 and 130.5 ng/mL, respectively), whereas both lopinavir and ritonavir were undetectable in all seminal plasma samples (< 30 ng/mL). All 10 patients had undetectable seminal plasma HIV-RNA at week 48 (< 2.3 log(10) copies/mL).
Conclusions: No local viral production was evident in semen, despite the local absence of therapeutic antiretroviral drug concentrations in the five patients receiving lopinavir/ritonavir alone.

• 出版日期2008-6