Semi-solid gels function as physical barriers to human immunodeficiency virus transport in vitro.
Vaginal gels may act as physical barriers to HIV during sexual transmission. However, the extent and significance of this effect are not well understood. During male-to-female sexual transmission of HIV, semen containing infectious HIV is present within the lower female reproductive tract. In cases where a topical gel has previously been applied to the vaginal epithelium, virions must move through gel layers before reaching vulnerable tissue. This additional barrier could affect the functioning of anti-HIV microbicide gels and placebos. To better understand HIV transport in gels, we: (1) quantified diffusion coefficients of HIV virions within semi-solid delivery vehicles; and (2) tested the barrier functioning of thin gel layers in a Transwell system. Two gels used as placebos in microbicides clinical trials, hydroxyethyl cellulose (HEC) and methylcellulose (MC), were found to hinder HIV transport in vitro. The diffusion coefficients for HIV virions in undiluted HEC and MC were 4±2 x 10⁻¹² and 7±1 x 10⁻¹² cm²/s, respectively. These are almost 10,000 times lower than the diffusion coefficient for HIV in water. Substantial gel dilution (80%:diluent/gel, v/v) was required before diffusion coefficients rose to even two orders of magnitude lower than those in water. In the Transwell system, gel layers of approximately 150-μm thickness reduced HIV transport. There was a log reduction in the amount of HIV that had breached the Transwell membrane after 0-, 4-, and 8-h incubations. The ability of a gel to function as a physical barrier to HIV transport from semen to tissue will also depend on its distribution over the epithelium and effects of dilution by vaginal fluids or semen. Results here can serve as a baseline for future design of products that act as barriers to HIV transmission. The potential barrier function of placebo gels should be considered in the design and interpretation of microbicides clinical trials.
Lai
Bonnie E
BE
Department of Biomedical Engineering, Duke University, Durham, NC 27708, USA.
Geonnotti
Anthony R
AR
Desoto
Michael G
MG
Montefiori
David C
DC
Katz
David F
DF
D000282:Administration, Intravaginal; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D002482:Cellulose / Q000031:analogs & derivatives; D004058:Diffusion; D015195:Drug Design; D005260:Female; D005782:Gels; D015658:HIV Infections / Q000517:prevention & control* / Q000635:transmission; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008297:Male; D008747:Methylcellulose; D014621:Vagina / Q000821:virology; D014622:Vaginal Creams, Foams, and Jellies / Q000008:administration & dosage / Q000627:therapeutic use
D019380:Anti-HIV Agents; D000890:Anti-Infective Agents; D005782:Gels; D014622:Vaginal Creams, Foams, and Jellies; D002482:Cellulose; C002283:hydroxyethylcellulose; D008747:Methylcellulose