Antiretroviral Zinc Microbicide Gel Protects Monkeys against HIV Infection

		SUMMARY: A vaginal microbicide gel containing zinc acetate and a small dose of MIV-150, an investigational NNRTI, protected female macaque monkeys from infection with an HIV-related virus for up to 24 hours, according to a study published this month in the open access online journal PLoS ONE. A gel containing zinc alone provided partial protection.

By Liz Highleyman

An HIV prevention method that can be used by women without cooperation from their male sexual partners is a key goal of researchers and advocates worldwide.

Microbicide products that act as simple barriers have not proven effective in studies to date, but the CAPRISA-2 findings reported this past summer demonstrate that microbicides containing antiretroviral drugs can be more effective.

However, using approved drugs that are widely utilized for HIV therapy as microbicide ingredients is potentially problematic, since this could lead to drug resistance that limits future treatment options for people who do become infected.

In the present study, Jessica Kenney from the Population Council in New York City and colleagues tested the efficacy of a combination microbicide gel containing zinc and micro-molar doses of the novel non-nucleoside reverse transcriptase inhibitor (NNRTI) MIV-150 in a carrageenan base. Prior studies have shown that a microbicide containing carrageenan alone (Carraguard) did not provide significant protection.

The researchers applied vaginal gels containing zinc plus MIV-150, zinc only, MIV-150 only, or placebo to adult female macaques every day for 2 weeks; in addition, some monkeys received gel applications every other day for 4 weeks. The animals were then "challenged" with non-traumatic vaginal administration of a hybrid human/monkey immunodeficiency virus known as SHIV-RT for up to 24 hours after the last gel application.

Results

	Repeated administration of a combination gel containing 14 mM zinc acetate and 50 mcM MIV-150 afforded full protection from HIV infection.
	None of the 21 monkeys treated with this gel formulation became infected up to 24 hours after 2 weeks of daily application.
	Gel containing zinc acetate alone produced partial protection (67% at 8-24 hours after application).
	Gel containing only MIV-150 produced less effective partial protection (56% at 8 hours, falling to 11% at 24 hours after the last application).
	A majority of monkeys (11 out of 14) were still protected when zinc/MIV-150 combination gel or zinc-only gel was applied every other day for 4 weeks.
	MIV-150 did not accumulate systemically after repeated application, and MIV-150-containing gels did not select for drug-resistant virus.

Based on these findings, the study authors concluded, "A combination MIV-150/zinc acetate gel and a zinc acetate gel provide significant protection against SHIV-RT infection for up to 24 hours."

"This represents a novel advancement, identifying microbicides that do not contain antiviral 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," they added.

Given that they also provided significant protection, the researchers recommended that gels containing zinc acetate alone "should also be considered for further development and human testing, since they are not expected to promote drug resistance."

Investigator affiliations; Population Council, New York, NY; Aaron Diamond AIDS Research Center, Rockefeller University, New York, NY; Tulane National Primate Research Center, Tulane University, Covington, LA; AIDS and Cancer Virus Program, SAIC-Frederick, National Cancer Institute, Frederick, MD.

1/11/11

Reference
J Kenney, M Aravantinou, R Singer, and others. An Antiretroviral/Zinc Combination Gel Provides 24 Hours of Complete Protection against Vaginal SHIV Infection in Macaques. PLoS ONE 6(1): e15835 (Free full text). January 2011.