JAC Advance Access originally published online on March 13, 2008
Journal of Antimicrobial Chemotherapy 2008 61(6):1344-1347; doi:10.1093/jac/dkn098
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Original research |
Absence of HIV-1 shedding in male genital tract after 1 year of first-line lopinavir/ritonavir alone or in combination with zidovudine/lamivudine
1 Laboratoire de Virologie, EA MRT 3620, Université René Descartes Paris 5, CHU Necker-Enfants Malades, Paris, France 2 Département de Médecine Interne et Maladies Infectieuses, CHU Bicêtre, Le Kremlin-Bicêtre, France 3 Laboratoire de Pharmacologie Clinique, CHU Bichat-Claude Bernard, Paris, France 4 Centre d’Investigation Clinique, CHU Necker-Enfants Malades, Paris, France 5 Département de Maladies Infectieuses, CHU Saint-Antoine, Paris, France 6 Département de Maladies Infectieuses, CHU Hôtel-Dieu, Nantes, France 7 Laboratoires Abbott, Rungis, France
Received 13 November 2007; returned 20 January 2008; revised 27 January 2008; accepted 17 February 2008
* Correspondence address. Département de Médecine Interne et Maladies Infectieuses, Centre Hospitalier Universitaire de Bicêtre, 78 rue du Général Leclerc, 94275 Le Kremlin-Bicêtre Cedex, France. Tel: +33-1-45-21-27-83; Fax: +33-1-45-21-26-32; E-mail: jade.ghosn{at}bct.aphp.fr
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 log10 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 log10 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.
Keywords: protease inhibitor , compartmentalization , semen , sanctuary site
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