title: Absence of HIV-1 shedding in male genital tract after 1 year of first-line lopinavir/ritonavir alone or in combination with zidovudine/lamivudine.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Laboratoire de Virologie, EA MRT 3620, Université René Descartes Paris 5, CHU Necker-Enfants Malades, Paris, France. jade.ghosn@bct.aphp.fr
authors.forename: Jade
authors.initials: J
authors.lastname: Ghosn
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Chaix
authors.forename: Gilles
authors.initials: G
authors.lastname: Peytavin
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Bresson
authors.forename: Julie
authors.initials: J
authors.lastname: Galimand
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Girard
authors.forename: François
authors.initials: F
authors.lastname: Raffi
authors.forename: Isabelle
authors.initials: I
authors.lastname: Cohen-Codar
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Delfraissy
authors.forename: Christine
authors.initials: C
authors.lastname: Rouzioux
mesh_terms: D019380:Anti-HIV Agents / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid; D004359:Drug Therapy, Combination; D005837:Genitalia, Male / Q000821:virology*; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D019259:Lamivudine / Q000627:therapeutic use; D008137:Longitudinal Studies; D061466:Lopinavir; D008297:Male; D010949:Plasma / Q000737:chemistry / Q000821:virology; D011744:Pyrimidinones / Q000493:pharmacokinetics / Q000627:therapeutic use; D012367:RNA, Viral / Q000302:isolation & purification; D019438:Ritonavir / Q000493:pharmacokinetics / Q000627:therapeutic use; D012661:Semen / Q000737:chemistry / Q000821:virology; D013997:Time Factors; D017201:Virus Shedding / Q000187:drug effects*; D015215:Zidovudine / Q000627:therapeutic use
chemical_list: D019380:Anti-HIV Agents; D011744:Pyrimidinones; D012367:RNA, Viral; D061466:Lopinavir; D019259:Lamivudine; D015215:Zidovudine; D019438:Ritonavir