title: Distribution of cell-free and cell-associated HIV surrogates in the female genital tract after simulated vaginal intercourse.
abstract: BACKGROUND
  Rational development of drugs to prevent human immunodeficiency virus (HIV) transmission benefits from an understanding HIV distribution in the female genital tract after intercourse. This study describes HIV distribution using surrogates of cell-free and cell-associated HIV and semen.
  
  
  METHODS
  Apheresis-derived, autologous, lymphocyte-rich cells radiolabeled with 3.7-MBq (100-μCi) indium 111 ((111)In)-oxine (cell-associated HIV surrogate) and 18.5-MBq (500-μCi) technetium 99m ((99m)Tc)-sulfur colloid (HIV-sized 100-nm particle, cell-free HIV surrogate) were resuspended in 3 mL of hydroxyethylcellulose gel (semen simulant) with gadoteridol and dosed via artificial phallus after simulated intercourse. Postdosing dual-isotope single photon emission computed tomography with computed tomography (SPECT/CT) and magnetic resonance (MR) images were acquired to determine the surrogates' distribution. Seven hours after dosing, vaginal biopsy and luminal samples were collected at discrete locations in 8 subjects.
  
  
  RESULTS
  SPECT/CT and MR analysis showed HIV and semen surrogate distribution with highest signal intensity in the vaginal pericervical area, without detectable signal in the uterus. One-third of the administered dose was retained in the female genital tract after 4 hours. Cell-free and cell-associated surrogate distribution coincided.
  
  
  CONCLUSIONS
  We demonstrate the feasibility of dual-isotope SPECT/CT and MR imaging to determine the distribution of HIV and semen surrogates after simulated intercourse without disrupting vaginal contents. Surrogate distribution suggests topical microbicides do not need to reach the uterus for efficacy.
authors.forename: Nicolette A
authors.initials: NA
authors.lastname: Louissaint
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Fuchs
authors.forename: Rahul P
authors.initials: RP
authors.lastname: Bakshi
authors.forename: Sridhar
authors.initials: S
authors.lastname: Nimmagadda
authors.forename: Yong
authors.initials: Y
authors.lastname: Du
authors.forename: Katarzyna J
authors.initials: KJ
authors.lastname: Macura
authors.forename: Karen E
authors.initials: KE
authors.lastname: King
authors.forename: Richard
authors.initials: R
authors.lastname: Wahl
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Goldsmith
authors.forename: Brian
authors.initials: B
authors.lastname: Caffo
authors.forename: Ying Jun
authors.initials: YJ
authors.lastname: Cao
authors.forename: Jean
authors.initials: J
authors.lastname: Anderson
authors.forename: Craig W
authors.initials: CW
authors.lastname: Hendrix
mesh_terms: D000328:Adult; D003075:Coitus / Q000502:physiology*; D005260:Female; D015658:HIV Infections / Q000635:transmission* / Q000821:virology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging; D049268:Positron-Emission Tomography; D011849:Radioactive Tracers; D019275:Radiopharmaceuticals; D012661:Semen / Q000166:cytology / Q000000981:diagnostic imaging*; D018709:Statistics, Nonparametric; D013671:Technetium Tc 99m Sulfur Colloid; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D014621:Vagina / Q000000981:diagnostic imaging / Q000502:physiology / Q000821:virology*; D055815:Young Adult
chemical_list: D011849:Radioactive Tracers; D019275:Radiopharmaceuticals; D013671:Technetium Tc 99m Sulfur Colloid