Abstract
Understanding the distribution of microbicide and human immunodeficiency virus (HIV) within the gastrointestinal tract is critical to development of rectal HIV microbicides. A hydroxyethylcellulose-based microbicide surrogate or viscosity-matched semen surrogate, labeled with gadolinium-DTPA (diethylene triamine pentaacetic acid) and 99mTechnetium-sulfur colloid, was administered to three subjects under varying experimental conditions to evaluate effects of enema, coital simulation, and microbicide or semen simulant over 5 h duration. Quantitative assessment used single photon emission computed tomography (SPECT)/computed tomography (CT) and magnetic resonance imaging (MRI) imaging, and sigmoidoscopic sampling. Over 4 h, radiolabel migrated cephalad in all studies by a median (interquartile range) of 50% (29-102%; P<0.001), as far as the splenic flexure (approximately 60 cm) in 12% of studies. There was a correlation in concentration profile between endoscopic sampling and SPECT assessments. HIV-sized particles migrate retrograde, 60 cm in some studies, 4 h after simulated ejaculation in our model. SPECT/CT, MRI, and endoscopy can be used quantitatively to facilitate rational development of microbicides for rectal use.
Publication types
-
Comparative Study
-
Evaluation Study
-
Research Support, N.I.H., Extramural
MeSH terms
-
Administration, Rectal
-
Adult
-
Anti-HIV Agents / administration & dosage
-
Anti-HIV Agents / metabolism*
-
Anti-HIV Agents / therapeutic use
-
Anti-Infective Agents, Local / administration & dosage
-
Anti-Infective Agents, Local / metabolism*
-
Anti-Infective Agents, Local / therapeutic use
-
Cellulose / administration & dosage
-
Cellulose / analogs & derivatives*
-
Cellulose / metabolism
-
Cellulose / therapeutic use
-
Coitus
-
Contrast Media
-
Diagnostic Imaging / methods*
-
Ejaculation
-
Enema
-
Feasibility Studies
-
Gadolinium DTPA / administration & dosage
-
Gels
-
HIV Infections / metabolism*
-
HIV Infections / pathology
-
HIV Infections / prevention & control
-
Humans
-
Magnetic Resonance Imaging
-
Pilot Projects
-
Radiopharmaceuticals / administration & dosage
-
Rectum / metabolism*
-
Rectum / pathology
-
Semen / metabolism
-
Sigmoidoscopy*
-
Technetium Tc 99m Sulfur Colloid / administration & dosage
-
Time Factors
-
Tissue Distribution
-
Tomography, Emission-Computed, Single-Photon
-
Tomography, X-Ray Computed
-
Unsafe Sex
Substances
-
Anti-HIV Agents
-
Anti-Infective Agents, Local
-
Contrast Media
-
Gels
-
Radiopharmaceuticals
-
Technetium Tc 99m Sulfur Colloid
-
Cellulose
-
hydroxyethylcellulose
-
Gadolinium DTPA