2010 & Beyond
BY Benjamin Ryan
November 18 2010 4:00 AM ET
Science has advanced at a snail’s pace in finding medications -- topical microbicides or oral preexposure prophylaxis -- that can prevent HIV transmission. Early studies of microbicides have informed further research, but they have so far failed to prove the agents can be effective.
Ian McGowan, a principal investigator of the Microbicide Trials Network, says the next few years will be sink or swim for microbicide research. If current studies show promise, a product may reach the market within 10 years, he predicts. Otherwise, all research will likely close up shop for good. “By 2020 we may have a toolbox,” McGowan says. “It may have pills in it; it may have gels. Depending on people’s circumstances, they may use one or the other, or they may use both.”
A big conundrum with both microbicide and PrEP research is in developing a proper dosing schedule for a product that is both convenient and effective to use in advance of unpredictable sexual encounters. Antiretroviral agents may take up to 12 hours to activate after they’re either ingested in pill form or placed in the vagina or rectum in a microbicide gel. One potential answer is the investigatory nucleoside analog EFdA, whose form mimics human cells, so it is recognized by the immune system and activated in only 15 minutes. Because it is so potent, it also lasts much longer than other antiretroviral agents.
Research is currently deducing whether administering a daily oral antiretroviral to high-risk HIV-negative populations can curb transmission. Assuming this method is effective, further studies will look to see if occasional doses -- a “disco pill,” in McGowan’s words -- are also effective. At that point, cost will become a major consideration. Will insurers pay? Will certain high-risk populations be willing to spend the money for such precautions? With luck, a successful drug would go off patent by 2020, allowing for cheaper generic versions and more widespread use.
Another option, however, is an occasional infusion of a long-acting HIV therapy, such as the potential nano formulation of Tibotec’s TMC278 compound, which the company is hoping will work as PrEP. In theory, the drug would last long enough once applied to provide protection for a month.
Test and Treat
While the jury is still out, recent signs indicate that scientists are beginning to move toward a greater consensus that starting antiretroviral treatment earlier now outweighs the risks of long-term therapy. The San Francisco department of health has made “test and treat” -- getting HIV patients on therapy as soon as possible after diagnosis -- its recommended policy.
Even if T-cell counts remain at healthy levels for years, it seems that untreated HIV still harms the body, leading to a higher risk of conditions down the line, like heart disease, cancer, and kidney failure. A University of Washington study published in The New England Journal of Medicine in 2009 found a significant survival benefit for people who began treatment when their T-cell counts were still above 500.
And also in 2009 the first randomized, controlled trial to compare the risks and benefits of earlier versus delayed treatment, the National Institutes of Health’s START study, began. The results of the study, expected by 2015, should finally provide a definitive answer to this long-running mystery. Additional research going on around the world will hopefully prove whether widespread antiretroviral treatment, by lowering overall “community viral load,” can in turn reduce infection rates.
By the middle of the decade half of all HIVers will be older than 50. As the population grays, research is putting its muscle behind trying to understand why HIV infection seems to lead to accelerated aging in long-term survivors. The research is particularly critical considering that, among the deaths in today’s older HIVers, one third are due to non–AIDS-related causes.
A major culprit under study is what’s known as immune inflammation, which has been shown to contribute to aging in non-HIVers. When any virus enters the body the immune system releases inflammatory cytokine cells. In the case of an ordinary flu, for example, these cells would help clear the body of the illness in a relatively brief period of time and would then retreat. However, in HIV patients this inflammation seems to last indefinitely and can cause major damage to other human cells. Antiretrovirals don’t stop this effect because the body maintains its inflammatory response to the low levels of virus still replicating in reservoirs. The consequence is an elevated risk of many potentially fatal conditions associated with advanced age, including heart disease, osteoporosis, diabetes, muscle wasting, liver damage, and Alzheimer’s.
The goal of research on this matter is twofold: First, to understand why HIVers have a higher incidence of age-related illnesses. And second, if inflammation is indeed a major source of the problem, to find some sort of anti-inflammatory agent that can tone down the body’s overreaction to the low levels of virus.
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