Researchers point in the direction of possible candidates in the anti-HIV arsenal
by Chael Needle
LifeGuide
[Treatment Horizons]
As we celebrate the transition of old into new, we might turn our attention to three new HIV/AIDS healthcare and treatment possibilities that bear consideration as they develop.
On the microbicide front, researchers led by Luiz Castello Branco, at the Oswaldo Cruz Institute, Brazil, are studying a topical algae-based gel that has been shown to be highly effective against the sexual transmission of HIV. Dolabella diterpene, derived from the algae Dictyota pfaffii, native to coastal Brazil, stopped ninety-five percent of HIV replication in immune system cells in the first phase of trials. The new gel works to inhibit two enzymes necessary in the process of viral replication and infection of other cells. Researchers foresee few side effects because it is a naturally occurring substance. The second phase is set to start in February; researchers hope that the gel will be available in seven years. No HIV-preventative microbicide is currently available.
Detecting drug-resistant strains of HIV, one of the most common culprits in the failure of antiretroviral therapy, as quickly as possible may give patients in treatment a better tool to predict the drugs to which they may develop resistance. Researchers at Duke University Medical Center have developed a seemingly more forward-looking way of determining which drug-resistant strains may be in a patient’s bloodstream: a highly sensitive test that detects particular genetic mutations in HIV known to be associated with particular forms of drug resistance. The key phrase here is “highly sensitive.” While current tests can detect drug-resistant strains if they comprise at least twenty percent of a patient’s viral load, this new test can detect these strains even if they comprise one percent of a viral load. The test also has a unique capability, at least among commercially available tests, to detect when a virus molecule has more than one mutation, which may be a boon
when it comes to detecting multiple drug-resistant strains.
The test, developed and researched by Feng Gao, M.D., associate professor of medicine, along with Fangping Cai, Haifeng Chen, Charles B. Hicks, John A. Bartlett, and Jun Zhu, may also provide more information about how HIV develops drug resistance and shed light on possible new treatments that could be more resistance-proof. Researchers have also suggested that the test may also hold the potential to detect mutations that confer drug resistance in infectious agents—beyond HIV—that cause disease, such as hepatitis B, hepatitis C, and tuberculosis. The researchers have applied for a patent on the technology, with an eye toward its commercial uses as a diagnostic test. The results will be published in the February issue of Nature Methods.
While currently available drug classes fight HIV within CD4 cells, CCR5 antagonists aim to work by preventing HIV from infecting cells via its main entry route, the CCR5 coreceptor. For treatment-naive patients, HIV uses the CCR5 coreceptor as an entryway in approximately eighty to eighty-five percent of these cases. In treatment-experienced patients, HIV uses the CCR5 coreceptor approximately fifty to sixty percent of the time. HIV can also use the CXCR4 coreceptor as an entryway. The tendency for the virus to use either or both is called “tropism.”
Maraviroc, an investigational CCR5 antagonist currently in ongoing Phase III trials, will be made available to HIV/AIDS patients with CCR5-tropic HIV-1 whose treatment options are few or none due to resistance or intolerance, announced Pfizer, the company that is researching the drug. Pfizer plans to establish a multinational Expanded Access Program (EAP) to make maraviroc available to this patient population. Enrollment of patients from over thirty countries will begin in the next few months, pending regulatory review and approvals of the EAP study protocol. Following review of the data from the two Phase III maraviroc registrational trials, Pfizer plans to submit applications for marketing approval in both the U.S. and Europe. In other ongoing trials researchers have been studying the effects of maraviroc in patients with HIV-1 that can use R5 and/or X4 coreceptors as entryways to cells.
Chael Needle wrote about viral load as a marker of disease progression in the December 2006 issue.
January 2007
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