Newsday - February 18, 2003
Laurie Garrett

"I am living in a country with one of the highest HIV rates in the world," said Zinhle Thabethe, a young South African singer. "You know the statistics, but we are those statistics. On Saturdays, we go to funerals for our friends, our neighbors, our families." As many in the audience quietly wept, Thabethe described how she is now strong and healthy, thanks to a pilot study that provides her antiretroviral therapy. Once, she awoke every morning asking God why she was cursed with AIDS. "Now I think 'Why me? Why do I get to live, while others next to me are dying without these drugs?'"

Her question set the stage last week for this year's annual gathering of the world's top HIV researchers, who find themselves in 2003 working on two, sometimes contradictory, tracks. They are trying to push the intellectual envelopes of biology to find better treatments, a vaccine, even a cure. At the same time, they are trying to figure out how to use imperfect drugs invented nearly a decade ago to save their patients and millions of the world's poor.

The longer AIDS clinicians treat American and European HIV patients, the more complicated their care becomes. New side effects, such as heart attacks and strokes, have emerged. The virus' ability to mutate and escape drug therapy is presenting endless challenges and controversies.

For example, patients who have been on anti-HIV drugs for many years are beginning to develop serious, often lethal, cardiovascular complications. A European study of 23,468 HIV patients, who averaged 39 years of age, found that 126 had suffered heart attacks - 36 of which were fatal. Statistically, for every additional year the patients are on HIV drugs, their risk of having heart attacks increases by 26 percent, according to study leader Dr. Friis Moller of the Copenhagen HIV Programme.

There is considerable controversy over why this is happening. Some researchers insist all of the drugs, or one particular element of HIV treatment, is responsible. Some argue, it's simply HIV itself, finding new ways to destroy those it infects. Still others argue that those with HIV also happen to be high-risk cardiac subjects.

Regardless of its causes, cardiovascular disease and a host of lipid complications seen in HIV patients are driving up medical costs. Though the prices of most anti-HIV drugs have come down considerably in recent years, and generic forms are available for as little as $300 a year in some poor countries, the overall price tag of HIV treatment in the United States is rising. Dr. Michael Saag's HIV group at the University of Alabama in Birmingham showed that patients who don't have cardiac or lipid complications require an average of $17,698 a year for drugs, medical visits and tests. But once they develop heart or lipid complications, costs jump to an average $20,099 a year, with most of the increase due to hospitalizations and medications to lower cholesterol and control heart disease.

There is also considerable controversy and confusion about what ought to be done when a patient develops mutant forms of HIV that are resistant to drugs. Some researchers argue that resistance renders the drugs useless and continued use will lead to worsening disease, even death.

One of the most hotly discussed studies presented at the conference was that of Stanford's Dr. David Katzenstein. His group described 33 pregnant women in Zimbabwe who received a single dose of nevirapine during labor to prevent passing the virus to their newborns. Within eight weeks after delivery, 40 percent of the mothers had drug-resistant, mutant HIV in their bloodstreams. And more significantly, 65 percent of the new mothers had nevirapine-resistant mutant viruses in their breast milk.

A research team from Johns Hopkins School of Medicine offered further evidence of nevirapine mutation, when using it in single dose therapy to pregnant women in Uganda. Eight weeks after receiving the drug, 18 out of 66 mothers had highly drug-resistant viruses in their blood. The team made another disturbing discovery: The mutation rates varied according to what type of HIV was in the mothers before they received nevirapine. This offers the grim prospect that the drug may be more or less dangerous in various parts of the world, depending on what HIV is circulating there. None of this surprised Dr. John Mellors, of the University of Pittsburgh. He said that, "there needs to be a fundamental debate about the use of nevirapine therapy for mother-to-child transmission."

For African women like Thabathe, such a debate is far from academic. In South Africa, in particular, debate has raged over which risk is better taken - the chance of a mother transmitting HIV to her baby or the chance that drug resistant strains might pose a hazard to either the mother or her breastfeeding child. Pediatrician Jennifer Read, of the National Institutes of Health in Bethesda, headed a multinational team effort to scrutinize dozens of studies from all over the world on breast- milk transmission of HIV. She found that of 1,000 babies breastfed for one year, 94 would become infected, with odds increasing the longer a child is nursed.

All of which indicates the odds of transmitting a drug-resistant virus are fairly high. " ... The horse is already out of the barn - there already is exposure [to nevirapine]," Columbia University pediatrician Stephen Arpadi said in an interview. " ... It's only money. We have other, better drugs. Why not get more resources and apply a better regimen?"

The problem may be in choosing that "better regimen," whether for mother-to-child transmission prevention or treatment of infected adults. Most doctors treating AIDS patients in the United States closely monitor them. When resistant strains appear, patients are switched to another cocktail of anti-HIV medicines, until the medicine chest is bare.

But Dr. Steven Deeks of the University of California in San Francisco told the conference this is a mistake. He presented evidence that even a mix of drugs to which the virus is resistant is usually better for the patient than switching. Deeks argued that the mutant viruses have to give up some of their most lethal features to fight off the drugs. When drugs are switched, the viruses mutate back into their prior, tougher forms, and the illness worsens.

Regardless, the pipeline of new drugs, "is fuller than it's been for a long time," Mellors said. "We are beginning to keep up with the virus," developing new strategies. The current drugs have been redesigned, making them easier to take and lowering their toxicities. Meanwhile, he insisted, the available therapies, "can be taken in a hut in resource-scare countries."

Thabethe told the conference she was thrilled to be standing before the scientists who years ago invented the triple-therapy drugs that keep her alive. "I know you are way past that now, talking about new drugs, resistance, and all kinds of complicated science that I don't understand," Thabethe said. "But I am still busy being amazed by triple-therapy."

030218
ND030205

Always watch for outdated information. This article first appeared in 2003. This material is designed to support, not replace, the relationship that exists between you and your doctor.

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, 2003. 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. .