A potent combination microbicide that targets SHIV-RT, HSV-2 and HPV

• Published in: PloS one Vol. 9; no. 4; p. e94547
• Main Authors: Kizima, Larisa, Rodríguez, Aixa, Kenney, Jessica, Derby, Nina, Mizenina, Olga, Menon, Radhika, Seidor, Samantha, Zhang, Shimin, Levendosky, Keith, Jean-Pierre, Ninochka, Pugach, Pavel, Villegas, Guillermo, Ford, Brian E, Gettie, Agegnehu, Blanchard, James, Piatak, Jr, Michael, Lifson, Jeffrey D, Paglini, Gabriela, Teleshova, Natalia, Zydowsky, Thomas M, Robbiani, Melissa, Fernández-Romero, José A
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.04.2014; Public Library of Science (PLoS)
• Subjects: Acetic acid; Acquired immune deficiency syndrome; AIDS; Alphapapillomavirus - drug effects; Alphapapillomavirus - physiology; Anal Canal - drug effects; Anal Canal - virology; Animals; Anorectal; Anti-Infective Agents - chemistry; Anti-Infective Agents - pharmacology; Antimicrobial agents; Biology and life sciences; Biomedical research; Caco-2 Cells; Care and treatment; Carrageenan; Carrageenan - chemistry; Carrageenan - pharmacology; Carrageenin; Councils; Diagnosis; Disease prevention; Female; Gels; HeLa Cells; Herpes simplex; Herpes Simplex - prevention & control; Herpes Simplex - virology; Herpesvirus 2, Human - drug effects; Herpesvirus 2, Human - physiology; Histology; HIV; Host-Pathogen Interactions - drug effects; Human immunodeficiency virus; Human papillomavirus; Humans; In vivo methods and tests; Infections; Laboratory animals; Macaca mulatta; Medicine and health sciences; Mice; Mice, Inbred BALB C; Microbicides; Papillomavirus infections; Papillomavirus Infections - prevention & control; Papillomavirus Infections - virology; Physiological aspects; Population; Preservatives; Pyridines - chemistry; Pyridines - pharmacology; Rectum; Rectum - drug effects; Rectum - virology; Research and Analysis Methods; Reverse Transcriptase Inhibitors - chemistry; Reverse Transcriptase Inhibitors - pharmacology; Risk factors; Sexually transmitted diseases; Simian Acquired Immunodeficiency Syndrome - prevention & control; Simian Acquired Immunodeficiency Syndrome - virology; Simian Immunodeficiency Virus - drug effects; Simian Immunodeficiency Virus - enzymology; Simian Immunodeficiency Virus - physiology; STD; Target acquisition; Treatment Outcome; Urea - analogs & derivatives; Urea - chemistry; Urea - pharmacology; Vagina; Vagina - drug effects; Vagina - virology; Viruses; Zinc; Zinc acetate; Zinc Acetate - chemistry; Zinc Acetate - pharmacology; New York; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0094547

Prevalent infection with human herpes simplex 2 (HSV-2) or human papillomavirus (HPV) is associated with increased human immunodeficiency virus (HIV) acquisition. Microbicides that target HIV as well as these sexually transmitted infections (STIs) may more effectively limit HIV incidence. Previously, we showed that a microbicide gel (MZC) containing MIV-150, zinc acetate (ZA) and carrageenan (CG) protected macaques against simian-human immunodeficiency virus (SHIV-RT) infection and that a ZC gel protected mice against HSV-2 infection. Here we evaluated a modified MZC gel (containing different buffers, co-solvents, and preservatives suitable for clinical testing) against both vaginal and rectal challenge of animals with SHIV-RT, HSV-2 or HPV. MZC was stable and safe in vitro (cell viability and monolayer integrity) and in vivo (histology). MZC protected macaques against vaginal (p<0.0001) SHIV-RT infection when applied up to 8 hours (h) prior to challenge. When used close to the time of challenge, MZC prevented rectal SHIV-RT infection of macaques similar to the CG control. MZC significantly reduced vaginal (p<0.0001) and anorectal (p = 0.0187) infection of mice when 10(6) pfu HSV-2 were applied immediately after vaginal challenge and also when 5×10(3) pfu were applied between 8 h before and 4 h after vaginal challenge (p<0.0248). Protection of mice against 8×10(6) HPV16 pseudovirus particles (HPV16 PsV) was significant for MZC applied up to 24 h before and 2 h after vaginal challenge (p<0.0001) and also if applied 2 h before or after anorectal challenge (p<0.0006). MZC provides a durable window of protection against vaginal infection with these three viruses and, against HSV-2 and HPV making it an excellent candidate microbicide for clinical use.