Newsday - June 15, 1998
Laurie Garrett - Staff Writer

So new strategies of prevention and research must be developed, experts say.

Globally, few of the tens of millions of people infected with HIV can afford currently available drugs, Dr. Peter Piot, director of the United Nations' AIDS program, UNAIDS, said in an interview. But some developing countries - notably those in Latin America - are trying to care for all their HIV and AIDS patients, despite the great cost.

"For these countries, our primary role is to keep drug prices low and offer technical support," Piot said, noting that UNAIDS can assist by negotiating drug prices with pharmaceutical manufacturers.

For the far poorer countries of Africa and Asia gripped by the majority of the world's HIV, Piot's team has developed a minimal package of care that governments are encouraged to achieve. This includes drug treatment to prevent tuberculosis and parasitic infections in the HIV-positive and treatment of opportunistic infections as they occur.

Meanwhile many HIV drugs - including protease inhibitors - are being manufactured and sold in poor countries.

"The problem is people use [the anti-HIV drugs] improperly," Piot said. "So it's the ideal situation for resistance development. We need to think of that because that could lead to a global public health crisis."

UNAIDS also strives to provide the inexpensive drug AZT to poor pregnant women. Studies show AZT can block HIV transmission to the baby.

University of California in San Francisco epidemiologist Andrew Moss thinks the benefits of anti-HIV drugs might be enhanced if more research were done on how patients take their drugs. Moss has studied homeless populations, for example, showing 90 percent of the HIV-positive among them are not on such drugs at all. And the treated 10 percent are not closely monitored by physicians.

"We don't know if we're creating a lot of resistant virus, but the first strains of multidrug-resistant HIV have been seen," Moss notes.

One way to help patients is to simplify the regimen. Several new drugs, some of them protease inhibitors, are being developed as once-a-day therapies, rather than the current three times a day. The typical HIV patient is taking 12 to 15 pills a day on a series of complicated schedules.

Throughout the western world, physicians and drug firms are trying to develop treatments for patients whose viruses have developed broad resistance to available therapy. So far, few salvage approaches appear particularly useful.

Now in clinical trial is T-20, a genetically engineered protein that blocks the virus' ability to fuse with a cell, a key step to infection. Though early data appear promising, the drug must be administered by continuous intravenous feeds, hardly likely to find widespread popularity.

Probably the most excitement revolves around attempts to block the receptors HIV uses to enter human cells. Ed Berger of the National Institute of Allergy and Infectious Diseases discovered one of these receptors, CXCR4. And Ned Landau of the Aaron Diamond AIDS Research Center found another, CCR5. If both receptors were blocked, Berger says, the virus probably couldn't spread. "People can live without CCR5," Berger said, "which is fortuitous." But if only CCR5 is blocked, HIV can transform itself into a virus that can use CXCR4.

"And unfortunately CXCR4 seems to be involved in a large number of things," Berger said. "It plays a role in cardiac development."

There may be another way to block the virus, Berger noted. HIV needs to open a cell door by, metaphorically speaking, turning several knobs simultaneously. Not only must the virus attach to the CCR5 or CXCR4 doorknobs, HIV must also turn the CD4 knob on the cell's surface, flip part of itself a special way and pop another part of itself into the cell membrane. Berger thinks there must be a multitude of ways to interfere in that sequence without causing severe toxicity in the patient.

Michael Malim of the University of Pennsylvania has found another target for drug development: the vif protein, which plays a poorly understood role in HIV infection. Experiments eliminating vif from the virus show that without it, the virus cannot infect a cell. Though no anti-vif drug has yet been developed, Malim believes it would be an excellent target for a wide range of viruses.
980615
ND980602

AEGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1980, 1998. AEGiS. All materials appearing on AEGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of AEGiS, or the party credited as the provider of the content. .