Physicians developing better strategies to begin anti-HIV therapies, says Jefferson researcher in JAMA editorial

November 27, 2001

Physicians are starting to get smarter about when to give powerful anti-HIV drugs to patients with no discernable symptoms of HIV infection. Two new studies in the Nov. 28 issue of the Journal of the American Medical Association (JAMA) add to growing evidence that certain cellular and molecular markers in the blood may help physicians gauge the appropriate time to begin treatment with HAART, or highly active antiretroviral therapy.

Rather than beginning treatment with HAART as soon as an individual finds out he or she is infected with HIV, physicians should pay close attention to the levels of CD4 lymphocytes, which is a measure of immune system strength, and HIV RNA, which represents the amount of virus present. According to Roger J. Pomerantz, M.D., professor of medicine, biochemistry and molecular pharmacology and chief of the division of infectious diseases at Jefferson Medical College of Thomas Jefferson University in Philadelphia, whose editorial accompanies the two new studies, this is a relatively new way of thinking. "When we treat people, we want tight control," says Dr. Pomerantz, who is also director of the Center for Human Virology at Jefferson Medical College. "You want no detectable virus. But it doesn't mean treat them early. Right now we know that we need to treat them at the appropriate time."

When HAART first burst on the medical scene several years ago, all those who were infected with HIV were recommended to receive treatment immediately. And with good reason. The drugs in many cases have changed AIDS from a death sentence into a chronic, manageable disease. The virus goes into hiding, plummeting to undetectable levels in the blood, lying dormant in so-called cellular reservoirs.

For all the good HAART has done for patients with HIV infection, it is not a panacea. The drugs are expensive, difficult to take and in some cases come with severe side effects, such as changes in fat distribution, lipid abnormalities, buffalo humps, wasting in the face and legs and diabetes.

These side effects have forced physicians to rethink who needs immediate therapy and who can wait.

According to Dr. Pomerantz, doctors can tell when patients need such treatment not only by clinical signs of disease but by measuring substitute markers in the blood - the CD4 lymphocyte count and HIV RNA - both of which estimate how well the immune system is working. These may be more valuable in gauging the progression of disease and deciding on the timing of treatment with HAART.

"People last year suddenly began saying, 'Hold off on treatment' until the numbers show it is appropriate," says Dr. Pomerantz. "That was just last year. That's a big change, and these studies will change the scene even more.

"These are very important papers," he says. "I predict they will change therapy for all HIV-infected individuals in the developed world." Previous studies showed that CD4 and HIV RNA measures could be used together. "The International AIDS Society and the Public Health Service came out recently with new criteria - if the viral load was more than 50,000 or the CD4 count was less than 350, then you treat. This was controversial and a real paradigm shift," he notes.

But specific recommendations may not hold up for all patients, Dr. Pomerantz points out. Some patients, particularly women, may progress to AIDS at a lower RNA level more quickly than men. Others progress very quickly with low CD4 counts to AIDS. Such patients should be closely monitored.

There is also some question whether or not a more robust immune reconstitution might occur in some patients more than others, he says. The immune systems of many patients who received HAART have been restored to a relatively healthy level.

"In the future, looking at HIV eradication, there may be subtle problems with the immune system that disappear if you let the CD4 count get too low," he says. "You might be able to wait to give HAART in some people below 200 - perhaps in young people who reconstitute the immune system much more quickly."

The next step, Dr. Pomerantz says, is to "dissect out the subgroups that may not fit in - they can wait longer before treatment, or should be treated earlier. Dissecting out these groups and stratifying them - we need to find out who fits into categories and who will and won't be helped by these statistics."

Thomas Jefferson University

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