title: Impact of antiretroviral therapy duration and intensification on isolated shedding of HIV-1 RNA in semen.
abstract: BACKGROUND
  Effective antiretroviral therapy (ART) dramatically reduces human immunodeficiency virus (HIV) transmission. However, isolated shedding of HIV type 1 (HIV-1) in semen (IHS) can occur in the absence of detectable viremia or genital infections. We hypothesized that ART intensification with medications active in semen might prevent IHS.
  
  
  METHODS
  Paired blood and semen samples were collected monthly for 6 months from HIV-infected men starting ART that was intensified (iART) with maraviroc and raltegravir in an open-label fashion. Semen parameters were compared to those of historical controls starting standard ART (sART).
  
  
  RESULTS
  Compared with 25 controls who started sART, the semen HIV-1 load in 13 subjects who started iART was more rapidly suppressed (P = .043). IHS was detected at >1 visit in 2 participants (15%) receiving iART and in 12 controls (48%) receiving sART (P = .040). Among iART recipients, IHS was associated with lower raltegravir concentrations in blood and semen, compared with complete HIV-1 suppression (P = .03). Prolonged, high-level IHS (ie, shedding of >5000 RNA copies/mL) was observed in 1 iART recipient (8%), despite rapid viremia suppression and therapeutic drug levels; for 10 months, this virus remained R5 tropic, drug susceptible, and similar in sequence to virus recovered from blood. IHS was not seen after >3 years of effective ART in a parallel, prospective cohort study.
  
  
  CONCLUSIONS
  iART transiently reduced the occurrence of IHS early after ART initiation but did not prevent high-level IHS. IHS was not seen after more prolonged sART.
authors: Department of Medicine, University of Toronto, Ontario, Canada. ebrendan.osborne@utoronto.ca
authors: Brendan J W
authors: BJ
authors: Osborne
authors: Prameet M
authors: PM
authors: Sheth
authors: Tae Joon
authors: TJ
authors: Yi
authors: Colin
authors: C
authors: Kovacs
authors: Erika
authors: E
authors: Benko
authors: Charles la
authors: Cl
authors: Porte
authors: Sanja
authors: S
authors: Huibner
authors: Anh Q
authors: AQ
authors: Le
authors: Ryan
authors: R
authors: Danroth
authors: Bemuluyigza
authors: B
authors: Baraki
authors: Tony
authors: T
authors: Mazzulli
authors: Zabrina L
authors: ZL
authors: Brumme
authors: Rupert
authors: R
authors: Kaul
mesh_terms: D000595:Amino Acid Sequence; D044966:Anti-Retroviral Agents / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D001483:Base Sequence; D016022:Case-Control Studies; D003510:Cyclohexanes / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy* / Q000635:transmission / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity; D006801:Humans; D015994:Incidence; D008297:Male; D000077592:Maraviroc; D008969:Molecular Sequence Data; D011446:Prospective Studies; D011760:Pyrrolidinones / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D000068898:Raltegravir Potassium; D012661:Semen / Q000821:virology*; D017423:Sequence Analysis, RNA; D012725:Sexual Behavior; D013997:Time Factors; D016896:Treatment Outcome; D014230:Triazoles / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D019562:Viral Load; D014766:Viremia / Q000821:virology; D017201:Virus Shedding
chemical_list: D044966:Anti-Retroviral Agents; D003510:Cyclohexanes; D011760:Pyrrolidinones; D012367:RNA, Viral; D014230:Triazoles; D000068898:Raltegravir Potassium; D000077592:Maraviroc