Using Tobacco to Prevent HIV
By Jeffrey Laurence, M.D.
January 17, 2006—Nature usually favors females.
Males have a shorter life expectancy, a higher death rate at all ages and, with the exception of autoimmune conditions, respond poorly to most diseases when compared to females. Sex differences are also seen in response to infections in adults and in infants, as demonstrated dramatically for mother-to-fetus transmission of most viruses and bacteria; the burden on males is typically twice that of females.
HIV is a major exception.
As eloquently reviewed by Dr. Kenneth Mayer, amfAR Program Board member, in the January 1, 2006 issue of the Journal of Infectious Diseases, the majority of HIV-infected women acquire the virus through heterosexual intercourse, and this reflects their inherent biological and social vulnerability. What is needed are prevention measures under a woman's control, such as microbicides.
A microbicide is a material—typically a foam, gel or cream resembling a vaginal lubricant or local contraceptive—which, when applied vaginally or rectally, blocks viral transmission.
Dr. Mayer points out that the concept of such anti-HIV protection has existed for over a decade, but there are many stumbling blocks. These include side effects; one promising anti-HIV microbicide, nonoxynol-9 (N-9), actually facilitated HIV spread in large clinical trials as it caused small abrasions in vaginal and cervical linings. Another is cost. Large pharmaceutical companies foresee very little profit in microbicides; the ideal product must be easy to manufacture from inexpensive raw materials, and easy to store.
Finally, there is the necessity for large clinical trials. Unexpectedly large: women in microbicide trials, both those receiving the test product and those receiving the placebo, are encouraged to use condoms, resulting in low rates of new HIV infections. While reducing new infections is always good news, this has already doomed two large microbicide trials—they had to be stopped early as they had no hope of ever proving that the test product was more effective than the placebo, despite the researchers having reached their patient enrollment goals.
All of these problems will require the types of innovative research amfAR promulgates. An example of one intriguing solution appeared in the December 2005 issue of FASEB Journal. amfAR grantee Dr. Julian Ma of St. George's Hospital Medical School in London took on an unusual challenge. He knew the doses of most microbicides needed to protect monkeys when the monkey AIDS virus is introduced into the vagina. He recognized that most would need to be applied at least 2-3 times per week. Scale that up to a minimum goal of protecting 10 million women, and one would need to produce more than 8,000 pounds of microbicide a year.
There was only one way that Dr. Ma could conceive of approaching that challenge in an economical manner, and it involved an unlikely health product: tobacco.
Dr. Ma reported on a unique method of making large amounts of one promising anti-HIV microbicide, cyanovirin. Cyanovirin is a small protein taken from a bacterium normally found in water. It latches on to the outer coat of all known AIDS viruses, preventing them from infecting a cell. Utilizing a nifty way of getting the gene that makes cyanovirin into plants—it's carried on a bacterium that infects a wide range of plants—Dr. Ma's group subverted a tobacco plant's normal protein engineering system into making industrial quantities of the microbicide.
The anti-HIV activity of the material made by the tobacco plant rivaled that of cyanovirin manufactured by standard means, even when it was not separated out from the tobacco plant's usual proteins. Ma noted that making cyanovirin in tobacco plants benefits from the low cost of initial investment, high output, and availability of such plants in the very areas hardest hit by the AIDS pandemic.
We'll keep you informed of Dr. Ma’s progress.
Dr. Laurence is senior scientific consultant for programs at amfAR.amfAR.