Complex HIV Treatments Demand Greater MD Expertise

 SAN FRANCISCO--As AIDS has become a chronic disease, not necessarily a fatal one, HIV-infected patients are increasingly turning to family physicians and other primary care providers for medical care. And such providers are getting on-the-job experience in delivering a very complex therapy--antiretroviral drugs.

"Not every primary care doctor will do antiretroviral therapy, and not all should. But we’re now being called on to be AIDS experts," Bruce Soloway, MD, said at the American Academy of Family Physicians 1998 Scientific Assembly. "We need to focus not only on understanding HIV and treating symptoms early but also on managing risk for the disease."

AIDS statistics tell the story. Between 1995 and 1997, for example, AIDS deaths in New York City dropped 60% to 65%. "We now know that the more intense the treatment--the more drugs used--the lower the death rate," said Dr. Soloway, vice president of the Institute for Family Health, New York City.

The turnaround in AIDS treatment--moving from single treatments to combinations of drugs--stems from the work of Dr. David Ho, of the Aaron Diamond AIDS Research Center, New York, showing that HIV can reproduce itself at an enormously high rate--10 billion new viral particles per day. These replications are a constant source of genetic diversity, producing strains resistant to single therapies such as zidovudine (Retrovir, AZT).

New combinations of powerful drugs, including the protease inhibitors, however, successfully suppress viral replication and the evolution of resistant strains. Yet weak antiretroviral therapy is surprisingly worse than no treatment at all.

"It is too weak to stop the virus from reproducing but strong enough to exert selective pressure that favors resistant strains," Dr. Soloway said. With no treatment, the virus continues to replicate but does not produce resistant strains.

A major problem with antiretroviral therapy is getting patients to adhere to it, he said. Many patients are taking 15 to 20 pills a day as therapy, and suffering serious side effects, such as elevated cholesterol, that may demand even more drugs. But when patients miss doses, or stop taking some of their drugs, they are in real danger. "That’s when resistant strains crop up," he said. And some patients already have highly resistant viruses when they start a new therapy.

"The key is to try to ensure that the first regimen is successful," Dr. Soloway said. To raise the chances of success, he advises using three agents, including one protease inhibitor; counseling the patients about how to adhere to a schedule for taking the drugs; and taking precautions to minimize side effects.

Unfortunately, cross resistance is common among HIV drugs of the same class, and there are currently only three classes of HIV agents. "That’s why salvage therapy is less likely to succeed than the initial therapy," Dr. Soloway said.

Primary care physicians need to take into account several factors when considering whether to treat HIV patients with antiretroviral therapy, including the likelihood of disease progression, the patient’s lifestyle and attitudes, and any obstacles to adherence to a drug regimen. Dr. Soloway advises starting treatment when the HIV viral load is greater than 5,000 copies/mL and the CD4 count is less than 500 cells/mm³.

"If the patient can’t adhere to a drug regimen, you’re actually doing more harm than good by treating him," Dr. Soloway said. "The result of partial treatment, or treatment in which the patient starts and stops taking the drugs, is the development of resistant virus."

If the drug therapy does need to be stopped for any reason--say the patient is pregnant and in the first trimester--all three drugs should be stopped at the same time, he added.

Providing pregnant women with antiretroviral therapy in the second and third trimester of pregnancy is beneficial, Dr. Soloway said. Since 1992 when AZT was first used in pregnancy, the risk of transmission from HIV-infected mothers to their babies has dropped from 25% to 8%.

"There’s a clear relationship between viral load and perinatal transmission," Dr. Soloway said. While acknowledging that there are no long-term safety studies on the use of these drugs in pregnancy, he noted that there has, to date, been no evidence of serious side effects.

Besides treating HIV patients, the primary care provider also needs to help patients reduce their AIDS risk, Dr. Soloway said. "Keep in mind the current statistics: Two-thirds of new AIDS patients are minorities, one-half are heterosexual, and one-third are women."

He pointed out that having another sexually transmitted disease, such as herpes or gonorrhea, increases a person’s risk of sexually transmitted HIV infection. "We need to emphasize to our patients that the more sex partners they have, the more they are at risk, and that condoms should be used in any sexual encounter outside of a monogamous relationship," Dr. Soloway said.