A human colorectal explant culture to evaluate topical microbicides for the prevention of HIV infection.
A human colorectal explant culture was developed to assess the safety and efficacy of topical microbicides proposed for use in humans. Because any product marketed for vaginal application will likely be used for anal intercourse, it is important to evaluate these products in colorectal explant tissue. Microbicides tested included cellulose acetate 1,2-benzenedicarboxylate (CAP), PRO 2000, SPL7013, Vena Gel, and UC781, along with their accompanying placebos. Colorectal tissues were exposed to microbicides overnight and either fixed in formalin to evaluate toxicity by histological analysis or placed in 1-(4,5-dimethylthiazol-2-yl)-3,5-diphenylformazan (MTT) to quantitatively determine tissue viability. Histological analysis showed minimal toxicity for CAP, UC781, and Vena Gel. Shedding of epithelium with intact lamina propria occurred for the PRO 2000 and SPL7013 products, and shedding of epithelium and necrosis of the lamina propria occurred in explants cultured with nonoxynol-9. The MTT assay confirmed these results for PRO 2000 (4% and 0.5%), SPL7013 (and placebo), and nonoxynol-9 but also demonstrated reduced viability for CAP. However, viability of tissues treated with all products was not significantly different from that of the medium control. Efficacy of the microbicides was evaluated by measuring human immunodeficiency virus type 1 (HIV-1) infection of explants in the absence or presence of products. All microbicide formulations tested were highly effective in preventing HIV infection. However, explants treated with some of the placebo formulations also exhibited a lower level of infection. Most of the products developed for vaginal application showed minimal toxicity and were effective in reducing HIV-1 infection in colorectal tissues. These results suggest that this model is useful for evaluating the safety and efficacy of topical microbicides when used rectally.
Abner
Sheila R
SR
HIV and Retrovirology Branch, Division of HIV/AIDS Prevention, National Center for HIV, STD, and TB Prevention, Centers for Disease Control and Prevention, Atlanta, and Surgical Service, Emory University School of Medicine, Decatur, Georgia, USA.
Guenthner
Patricia C
PC
Guarner
Jeannette
J
Hancock
Kelly A
KA
Cummins
James E
JE
Fink
Aaron
A
Gilmore
G Thomas
GT
Staley
Charles
C
Ward
Albert
A
Ali
Odessa
O
Binderow
Sander
S
Cohen
Stephen
S
Grohskopf
Lisa A
LA
Paxton
Lynn
L
Hart
Clyde E
CE
Dezzutti
Charlene S
CS
D000890:Anti-Infective Agents / Q000494:pharmacology*; D044966:Anti-Retroviral Agents / Q000494:pharmacology* / Q000633:toxicity; D002478:Cells, Cultured; D003106:Colon / Q000187:drug effects / Q000473:pathology; D004353:Drug Evaluation, Preclinical; D015658:HIV Infections / Q000517:prevention & control*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000473:pathology; D009336:Necrosis / Q000473:pathology; D009924:Organ Culture Techniques
D000890:Anti-Infective Agents; D044966:Anti-Retroviral Agents