HIV This Week

Saxena BB, Han YA, Fu D, Rathnam P, Singh M, Laurence J, Lerner S. Sustained release of microbicides by newly engineered vaginal rings. AIDS. 2009 May;23(8):917-22.

An effective vaginal microbicide against sexual HIV transmission remains elusive, with requirements for adherence to appropriate application of effective, nontoxic products being a major deterrent. Saxena and colleagues explored methods to enable sustained release of combinations of antiretroviral microbicides, utilizing intravaginal rings composed of biosoluble Acacia gum or non-biodegradable hydrogel of 2-hydroxyethyl methacrylate and sodium methacrylate, materials approved for use by the United States Food and Drug Administration. The reverse transcriptase inhibitors TMC120, PMPA, 3’-azido-3’-deoxythymidine, and a newly characterized anti-HIV agent, Boc-lysinated betulonic acid, were incorporated into vaginal rings with different combinations. Daily and cumulative release rates of these inhibitors in ring eluates were determined by high-performance liquid chromatography, gas chromatography, or immunoassay. Anti-HIV effects were measured by assessment of p24 Gag antigen in T-cell cultures exposed to HIV-1 isolates. Drug release rates were sustained at concentrations higher than the minimum effective dose for HIV inhibition. The release was maintained for no less than 15 and 28 days from the Acacia gum and 2-hydroxyethyl methacrylate and sodium methacrylate rings, respectively. Boc-lysinated betulonic acid showed more than 90% inhibition of HIV-1 infection in H9 cells, with little toxicity to normal cells. The intravaginal rings described here are capable of efficacious drug delivery. Incorporation of several antiretroviral agents, including betulinol derivatives, which act at multiple levels of the HIV life cycle, may provide a synergistic effect to achieve higher efficacy on the inhibition of HIV infection.

Editors’ note: Although many participants in microbicide gel trials report the unexpected benefit of improved sexual satisfaction with gel use, work is proceeding with alternate microbicide delivery systems that have other potential advantages. Those include sustained delivery through a ring that could be put into position monthly, for example. Not having to insert a microbicide before each sex act would likely appeal to many women, particularly if the vaginal ring releases locally active, effective, and safe antiretroviral drugs for prevention.

Legal barriers to conducting public health research on methods of protection for anal intercourse were lifted in the United States in 2003 when the US Supreme Court invalidated all state antisodomy laws. Although research funding has been available for the development of rectal microbicides, the female condom, which has already been approved for vaginal use, has not been evaluated for anal use. Although there is no evidence that the female condom is safe for anal intercourse, it has already been taken up for off-label use by some men who have sex with men. This demonstrates the urgent need for more protection options for anal intercourse and, more immediately, the need to evaluate the safety and efficacy of the female condom for anal intercourse.

Editors’ note: Among men aged 25 to 44 years in the USA, 3.9% report having had anal sex with another man and 40% report having had anal sex with a woman. It is estimated that four times as many women in the USA practice anal sex than do men who have sex with men. Although the ‘female condom’ is recommended by some health providers and health promoters for anal sex, it has not been assessed for safety, ease of insertion (for example, should the inner ring be removed?), or efficacy. With the development and testing of rectal microbicides lagging behind vaginal products, quick studies to determine the optimal method for using the female condom during anal intercourse are needed now.

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