title: No virological failure in semen during properly suppressive antiretroviral therapy despite subtherapeutic local drug concentrations.
abstract: OBJECTIVE
  The aim of the study was to investigate whether drug resistance occurs earlier in seminal than in blood plasma with the use of such HAART regimens, of which only the two NRTIs achieve therapeutic concentrations in seminal plasma.
  
  
  METHODS
  Seminal and blood plasma of 12 patients, for 48-96 weeks on suppressive first-line therapy with saquinavir/ritonavir/didanosine/lamivudine, nelfinavir/didanosine/stavudine, or efavirenz/lamivudine/zidovudine were prospectively evaluated for HIV-1-RNA resistance mutations and drug concentrations.
  
  
  RESULTS
  Saquinavir, nelfinavir, and efavirenz blood plasma concentrations were in the therapeutic range. Nelfinavir and efavirenz seminal plasma concentrations were below the limit of quantification. In only 2 of 9 seminal plasma samples, from 1 of 6 patients, the saquinavir concentration was above the minimum therapeutic level. The seminal plasma HIV-1-RNA concentration remained undetectable in all patients up to 96 weeks, and therefore drug resistance could not be demonstrated. Thus, despite suboptimal local drug concentrations, no virological failure occurred in seminal plasma after prolonged first-line HAART.
  
  
  CONCLUSIONS
  This finding supports the hypothesis that the source of HIV in semen is a spillover from the blood/extraluminal tissue and that therefore seminal plasma drug levels may not be critical for viral suppression within the lumen of the male genital tract.
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases, Tropical Medicine and AIDS, Academic Medical Centre, University of Amsterdam, Amsterdam. Lowe@LMIB.azM.nl
authors.forename: Selwyn H
authors.initials: SH
authors.lastname: Lowe
authors.forename: Annemarie M J
authors.initials: AM
authors.lastname: Wensing
authors.forename: Jacqueline A H
authors.initials: JA
authors.lastname: Droste
authors.forename: Reinier W
authors.initials: RW
authors.lastname: ten Kate
authors.forename: Suzanne
authors.initials: S
authors.lastname: Jurriaans
authors.forename: David M
authors.initials: DM
authors.lastname: Burger
authors.forename: Jan C C
authors.initials: JC
authors.lastname: Borleffs
authors.forename: Joep M A
authors.initials: JM
authors.lastname: Lange
authors.forename: Jan M
authors.initials: JM
authors.lastname: Prins
mesh_terms: D019380:Anti-HIV Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D008297:Male; D012661:Semen / Q000737:chemistry*
chemical_list: D019380:Anti-HIV Agents