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Prostratin: A new therapeutic agent targeting viral reservoirs
Microbicides: An essential new HIV prevention strategy
Prostratin: A new therapeutic agent targeting viral reservoirs
The positive impact of current anti-HIV treatments in decreasing the rate of AIDS progression and death among people living with HIV is undeniable. However, several studies show that even in patients with undetectable plasma viremia (<50 copies/ml), virus rebounds after the interruption of Highly Active Antiretroviral Therapy (HAART) due to the presence of pockets – or reservoirs – of latently infected cells. It is now clear that HAART alone cannot cure HIV. And since the long-term use of HAART is associated with metabolic disorders and toxicities, the identification of new anti-HIV agents with novel mechanisms of action is an important therapeutic goal.
Prostratin was initially isolated as the active constituent of extracts of the tropical plant, homalanthus nutans, used in traditional Samoan herbal medicine for the treatment of “yellow fever” (i.e., hepatitis). The potent antiviral activity of prostratin, combined with its ability to activate HIV expression from latently infected cells, indicates that prostratin may be an important candidate for further development in new anti-HIV therapeutic protocols.
In May of 2001, AIDS Research Alliance was granted an exclusive license by the National Institutes of Health (NIH) to develop prostratin as an anti-HIV drug targeting viral reservoirs. In conjunction with this license, ARA announced in November 2001 a landmark agreement to benefit the people of Samoa, whose indigenous healers have used prostratin medically for generations.
AIDS Research Alliance was then awarded an NIH grant under the NIH-Development of AIDS Related Therapeutics Program (NIH-DART) to perform pre-clinical studies for prostratin. AIDS Research Alliance also established collaborations with multiple laboratories to examine in more detail the latent virus-activating property of prostratin. Results from these experiments have been encouraging. In July 2005, AIDS Research Alliance signed an agreement with a major contract research organization to conduct the remaining pharmacokinetic and toxicology studies of prostratin. The results of these experiments are pending.
- Prostratin Review
- Prostratin Update - 2006
- Prostratin FAQ
- Korin et al., J. Virology, 76 (16), 8118-23, 2002
- Witvrouw et al., Antiviral Chemistry & Chemotherapy, 14:321-328, 2003
- Brooks et al., Immunity, 19 (3), 413-23, 2003
- Biancotto et al, J Virology, 78:10507-15, 2004
- Rullas et al., J Antiviral Chemistry & Chemotherapy 9:545-54, 2004
- (PKC) in response to prostratin or PMA. A paper was published in the journal Antiviral Chemistry & Chemotherapy (Hezareh et al., Antiviral Chemistry & Chemotherapy, 15:207-22., 2004).
Microbicides: An essential HIV prevention strategy
There is an urgent need for more methods to prevent HIV infection, especially those that put women in control. Microbicides are synthetic or natural substances – manufactured in the form of a gel, cream, suppository or film – that can neutralize or kill a microbe. Unlike condoms, an HIV microbicide could be used without the cooperation or knowledge of one’s sexual partner, offering women (and men) who lack the power to avoid sex with partners who may be HIV-infected.
Sexual contact now accounts for 95% of all HIV infections worldwide. In North America the most common sexual practice that leads to HIV infection remains anal sex. Far from being limited to men who have sex with men (MSM), more scientific reports and popular media coverage suggest that it is also a widely practiced sexual behavior in the general heterosexual population, particularly in younger people. It is well established that unprotected anal intercourse (UAI) is a risk for the development of Sexually Transmitted Disease (STD) and HIV infection in men. However, much less is known about the contribution of anal sex, and unprotected intercourse (UI) in particular, to HIV infection in women.
Vaginal microbicide development is already advanced both in the United States and abroad with several Phase III efficacy trials currently underway in Africa. Rectal microbicide development, by comparison, is in its infancy. There are critical basic questions about anal intercourse that need to be answered first. These questions relate to the behavior before, during and after anal sex, and what happens physically to the anal canal and rectum with penetration. Investigators at AIDS Research Alliance, in collaboration with UCLA, are planning studies to address these important questions. The UCLA/ARA study proposes to investigate how anal sex is commonly practiced, what symptoms individuals who have anal sex experience and how they would prefer to apply a potential rectal microbicide.
The study will recruit approximately 900 subjects in Baltimore and Los Angeles with the aim of reaching a wide range of ethnic groups and age ranges of HIV-positive and HIV-negative men and women.
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