Abstract | BACKGROUND: METHODS AND FINDINGS: Rhesus macaques were vaginally challenged with SHIV-RT up to 24 h after repeated administration of microbicide versus placebo gels. Infection status was determined by measuring virologic and immunologic parameters. Combination microbicide gels containing 14 mM zinc acetate dihydrate and 50 µM MIV-150 afforded full protection (21 of 21 animals) for up to 24 h after 2 weeks of daily application. Partial protection was achieved with the MIV-150 gel (56% of control at 8 h after last application, 11% at 24 h), while the zinc acetate gel afforded more pronounced protection (67% at 8-24 h). Marked protection persisted when the zinc acetate or MIV-150/ zinc acetate gels were applied every other day for 4 weeks prior to challenge 24 h after the last gel was administered (11 of 14 protected). More MIV-150 was associated with cervical tissue 8 h after daily dosing of MIV-150/ zinc acetate versus MIV-150, while comparable MIV-150 levels were associated with vaginal tissues and at 24 h. CONCLUSIONS: A combination MIV-150/ zinc acetate gel and a zinc acetate gel provide significant protection against SHIV-RT infection for up to 24 h. This represents a novel advancement, identifying microbicides that do not contain anti-viral agents used to treat HIV infection and which can be used repeatedly and independently of coitus, and underscores the need for future clinical testing of their safety and ability to prevent HIV transmission in humans.
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Authors | Jessica Kenney, Meropi Aravantinou, Rachel Singer, Mayla Hsu, Aixa Rodriguez, Larisa Kizima, Ciby J Abraham, Radhika Menon, Samantha Seidor, Anne Chudolij, Agegnehu Gettie, James Blanchard, Jeffrey D Lifson, Michael Piatak Jr, Jose A Fernández-Romero, Thomas M Zydowsky, Melissa Robbiani |
Journal | PloS one
(PLoS One)
Vol. 6
Issue 1
Pg. e15835
(Jan 05 2011)
ISSN: 1932-6203 [Electronic] United States |
PMID | 21246052
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Anti-Retroviral Agents
- Drug Combinations
- Gels
- MIV 150
- Pyridines
- Urea
- HIV Reverse Transcriptase
- Zinc Acetate
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Topics |
- Administration, Intravaginal
- Animals
- Anti-Retroviral Agents
(administration & dosage)
- Drug Combinations
- Female
- Gels
(administration & dosage, therapeutic use)
- HIV Reverse Transcriptase
(antagonists & inhibitors)
- Humans
- Macaca
- Pyridines
(administration & dosage, therapeutic use)
- Simian Acquired Immunodeficiency Syndrome
(prevention & control)
- Simian Immunodeficiency Virus
- Treatment Outcome
- Urea
(administration & dosage, analogs & derivatives, therapeutic use)
- Zinc Acetate
(administration & dosage, therapeutic use)
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