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

Author(s): Ghosn J, Chaix ML, Peytavin G, Bresson JL, Galimand J, Girard PM, Raffi F, Cohen-Codar I, Delfraissy JF, Rouzioux C

Affiliation(s): Laboratoire de Virologie, EA MRT 3620, Universite Rene Descartes Paris 5, CHU Necker-Enfants Malades, Paris, France. jade.ghosn@bct.aphp.fr

Publication date & source: 2008-06, J Antimicrob Chemother., 61(6):1344-7. Epub 2008 Mar 13.

Publication type: Comparative Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't

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.