Over-the-counter personal lubricants are used frequently during vaginal and anal intercourse, but they have not been extensively tested for biological effects that might influence HIV transmission. We evaluated the in vitro toxicity anti-HIV-1 activity and osmolality of popular lubricants. A total of 41 lubricants were examined and compared to Gynol II and Carraguard as positive and negative controls for toxicity, respectively. Cytotoxicity was assessed using the XTT assay. The MAGI assay with R5 and X4 HIV-1 laboratory strains was used to evaluate antiviral activity. The effect of the lubricants on differentiated Caco-2 cell monolayers (transepithelial electrical resistance, TEER) was also measured. None of the lubricants tested showed significant activity against HIV-1. Surprisingly, four of them, Astroglide Liquid, Astroglide Warming Liquid, Astroglide Glycerin & Paraben-Free Liquid, and Astroglide Silken Secret, significantly enhanced HIV-1 replication (p<0.0001). A common ingredient in three of these preparations is polyquaternium-15. In vitro testing of a chemically related compound (MADQUAT) confirmed that this similarly augmented HIV-1 replication. Most of the lubricants were found to be hyperosmolar and the TEER value dropped approximately 60% 2 h after exposure to all lubricants tested. Cells treated with Carraguard, saline, and cell controls maintained about 100% initial TEER value after 2-6 h. We have identified four lubricants that significantly increase HIV-1 replication in vitro. In addition, the epithelial damage caused by these and many other lubricants may have implications for enhancing HIV transmission in vivo. These data emphasize the importance of performing more rigorous safety testing on these products.

Abstract:We report the development of a combined confocal Raman spectroscopy (CRS) and optical coherence tomography (OCT) instrument (CRS-OCT) capable of measuring analytes in targeted biological tissues with sub-100-micron spatial resolution. The OCT subsystem was used to measure depth-resolved tissue morphology and guide the acquisition of chemically-specific Raman spectra. To demonstrate its utility, the instrument was used to accurately measure depth-resolved, physiologicallyrelevant concentrations of Tenofovir, a microbicide drug used to prevent the sexual transmission of HIV, in ex vivo tissue samples.

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Objective-We used a new optical imaging technique to compare human intravaginal coating distributions of Conceptrol® and Advantage™. These gels are surrogates for future microbicidal gels, differing in molecular structures and biophysical properties.Methods-For each protocol, a 3-mL gel bolus was inserted to the posterior fornix while the woman was in the supine position. She then either: (1) remained supine (10 min); or (2) sat up (1 min), stood up (1 min), sat down (1 min), and returned to supine for a net elapsed time of 10 min. The imaging device is sized/shaped like a phallus, and measurements while the device was inserted provide data that simulate peri-intromission coating.Results-Coating by Advantage™ was more extensive and uniform than coating by Conceptrol®, with smaller bare spots of uncoated epithelium. Change in posture tended to increase extent and uniformity of coating, details differing between gels.Conclusions-Results are consistent with predictions of mechanistic coating theory, using gel rheological data as inputs.

An optical device has been developed for imaging the human vaginal epithelial surfaces, and quantitatively measuring distributions of coating thickness of drug delivery formulations—such as gels—applied for prophylaxis, contraception or therapy. The device consists of a rigid endoscope contained within a 27-mm-diam hollow, polished-transparent polycarbonate tube (150mm long) with a hemispherical cap. Illumination is from a xenon arc. The device is inserted into, and remains stationary within the vagina. A custom gearing mechanism moves the endoscope relative to the tube, so that it views epithelial surfaces immediately apposing its outer surface (i.e., 150mm long by 360° azimuthal angle). Thus, with the tube fixed relative to the vagina, the endoscope sites local regions at distinct and measurable locations that span the vaginal epithelium. The returning light path is split between a video camera and photomultiplier. Excitation and emission filters in the light path enable measurement of fluorescence of the sited region. Thus, the instrument captures video images simultaneously with photometric measurement of fluorescence of each video field [∼10mm diameter; formulations are labeled with 0.1%w∕w United States Pharmacoepia (USP) injectable sodium fluorescein]. Position, time and fluorescence measurements are continuously displayed (on video) and recorded (to a computer database). The photomultiplier output is digitized to quantify fluorescence of the endoscope field of view. Quantification of the thickness of formulation coating of a surface sited by the device is achieved due to the linear relationship between thickness and fluorescence intensity for biologically relevant thin layers (of the order of 0.5mm). Summary measures of coating have been developed, focusing upon extent, location and uniformity. The device has begun to be applied in human studies of model formulations for prophylaxis against infection with HIV and other sexually transmitted pathogens.