Newsday - August 29, 1989
Laurie Garrett

Most base their treatment decisions on T-cell counts, the levels of the immune system's disease-fighting T4 cells versus the suppressive T-8 cells. When T-4 cell counts drop precipitously physicians are moved to take action, even if the patient has no other symptoms.

At Downstate Medical Center in Brooklyn, says Dr. Sheldon Landesman, anyone with a T4 count below 200 istreated prophylactically with either the drug bactrim or aerosolized pentamidine to prevent pneumonia.

The Downstate group also starts HIV patients on AZT (azidothymidine) therapy when the T-cell count drops. Although the drug does seem to slow down the disease process by attacking viral reproduction, it does have serious drawbacks; over time it destroys bone marrow, leading to life-threatening anemia. Less than 20 percent of all people with HIV are able to tolerate the drug for six months or more, according to the National Cancer Institute. But until alternative anti-HIV drugs are available, said Landesman, AZT remains essential.

Landesman and colleague Dr. William McCormick said it's not uncommon to see a patient gain over 40 pounds within a few weeks of starting AZT therapy. "They really pork right up," chuckled McCormick. "The disease stabilizes, and they feel better."

Dr. Lawrence Deyton of the National Institute of Allergy and Infectious Diseases said he has a long talk with his patients when their T-cell count drops below 200. "I say, this is where you are, and these are the therapies that are open to you."

He, too, recommends AZT and aerosolized pentamidine. "And I say my job, at that point, is to help you understand your disease."

San Francisco General Hospital's Dr. Donald Abrams looks at a combination of falling T-cell count and lymph node inflammation as a cue that it is time to start therapy. But AZT is not the only option he provides. "Basically at that point I tell them about all the protocols [experimental drug programs] that are available and increase their appointments to every three months, so I can watch them closely."

Overdependence on T-cell count can be risky, and Dr. Richard DiGioia of Washington, D.C., has documented wild fluctuations that do not correlate well with the disease state. "This is one reason I remain uncertain as to the exact benefit of early use of AZT," DiGioia said.

There is another problem - resistance," said Downstate's Dr. Jack Dehovitz. "Patients seem to get clear benefit from AZT for somewhere between six and eighteen months, but then the disease takes its course. And we assume the virus has become resistant to AZT."

RESEARCHERS ALL OVER the world have noted the AZT resistance problem, and Dehovitz anticipates HIV treatment will shortly become more complicated as other anti-viral drugs - such as ddI and ddC, which are still being tested - become available. Then, he said, physicians will start a patient on, for example, AZT and switch to ddI when resistance develops.

During the asymptomatic stage of HIV infection many patients, regardless of their T-cell count, choose to concentrate on changing their lifestyle, sleeping more, stopping drug and alcohol use and altering their diet in the belief these efforts will help their bodies fight off the virus. "None of this is proven to help," Abrams said. "The key word here is evidence - there isn't any."

NIAID's Deyton is also skeptical, but said, "My own gestalt is that someday somebody will go to Stockholm to pick up the Nobel Prize for isolating the substance that is emitted in the brain during stress, that down-regulates the immune system. We all know it's there, we just can't find it." Deyton tells his patients to find some sort of stress reduction that works for them: meditation, exercise, reduced work load.

Most people learn they have AIDS, however, long after they were initially infected and have developed symptoms. Typically, the first symptoms include shortness of breath caused by pneumonia parasites, purplish spots on the skin - which are Kaposi's sarcoma tumors - rapid weight loss, diarrhea and a variety of lingering infections indicative of a damaged immune system. At that point the T cells have already been devastated, and the body is falling victim to a legion of microorganisms that, to a healthy person, are harmless or easily treated.

The AIDS-ologist then becomes an infectious disease specialist, monitoring and treating herpes, yeast infections, pneumonia, parasites and bacteria in the brain, viral attacks on the eyes and a host of agents that destroy the digestive system. Cancer, too, becomes a problem as tumors develop on the skin, in the lymphatic system and in the brain.

Dehovitz has found that patients who fail to get treated early for such opportunistic infections are at greater risk for a second bout later on. "We see people who don't come in here for PCP treatment until they're literally gasping for breath trying to make it up the stairs," he said, "and the damage to their lungs is severe."

If, however, the patient sees a physician at the first sign of each new AIDS-related illness, there is a reasonably effective arsenal of medical weapons to draw upon for treatment of some opportunistic infections and tumors:

Acyclovir attacks both herpes simplex and zoster viruses.

Tuberculosis, an increasingly common problem among HIV-infected people, is treated with antibiotics, such as isoniazid and rifampin.

Fluconizole shows promise in the prevention of cryptoccocal meningitis, a devastating brain disease that causes dementia. If the disorder develops, amphotericin B treatment can help.

Another brain infection, produced by toxoplasmosis, may at times be treated with pyrimethamine.

Candida yeast infections are tackled with clotrimazole and ketoconazole.

Ribavirin and gamma globulin injections may help slow the disease process in HIV-infected babies, although both uses are highly controversial.

Nevertheless, some infections defy treatment. For example, nobody can explain what agents are responsible for the wasting syndrome and dramatic weight loss in AZT patients. Cryptosporidia parasites are at least partially responsible and cannot, as yet, be controlled effectively with any medication.

Nearly half of all AIDS patients suffer from mycobacterium avium, a bacterial disease of the lungs that promotes the typical wasting syndrome. There is no effective therapy.

Although 10 percent of all AIDS patients suffer blood disorders related to their decreased ability to produce blood clots, there is no standard therapy for this problem.

Except for Kaposi's sarcoma, the tumors associated with AIDS have thus far defied effective treatment.

Finally, many of the drugs cannot be tolerated by babies and small children infected with HIV. Infant care requires tremendous expertise and is best handled at one of the nation's regional centers for pediatric AIDS.

A key factor complicating pediatric treatment is the inability to diagnose HIV infection in the first 12 to 18 months of life. During that time, the child does not produce antibodies of its own, but has received antibodies from the mother. As a result, HIV blood tests only detect the mother's antibodies.

THE DIFFICULTY, said pediatrician Jim Oleske of Newark's Children's Hospital, cuts profoundly to the core of medical ethics. "There are plenty of reasons to think starting treatment with AZT and bactrim and other drugs right at birth would hold off the virus," he said. But only half the children born to HIV-positive mothers are infected. "Do we wait to confirm the baby is infected before giving it a toxic drug or go ahead and treat?" Oleske asked.

Even more troubling for Oleske are the ethical debates surrounding possible in utero treatment of fetuses. There is a growing sentiment in favor of giving HIV-positive mothers AZT during the third trimester of pregnancy in hopes of preventing infection of the fetus. "That one's a close call," Oleske said. "I'm really not sure how I feel about it."

In the long run, American AIDS care increasingly resembles cancer treatment, which draws upon a battery of drugs and other treatments, all of which have loathsome side effects. Oncologists now view most cancers as chronic diseases that may persist for several years and require a high level of physician expertise.

Similarly, a racial gap exists in disease survival time for both cancer and AIDS. Black women and children, for example, rarely survive two years after HIV diagnosis, compared to over five years for white males. Similarly, whites are more likely than blacks to survive all types of cancer longer than five years.

"Look," said Oleske, "we're talking about a disease [AIDS] that is increasingly hitting poor people. And that means poor people's medicine, which is frankly terrible in this country."

* * *

Drug Options

The following have been approved by the Food and Drug Administration for the treatment of AIDS and related disorders.

Drug: (AZT) Azidothymidine

Target: HIV

Goal of Treatment: Block viral reproduction and slow the progression of the AIDS disease process

For Whom: Patients who have had pneumocystis carinii pneumonia (PCP) or have a T-cell count lower than 500

Shortcomings: Pills must be taken every four hours, requiring patients to interrupt sleep. Can cause severe anemia, bone marrow depletion or fatigue; the drug may be too dangerous for some patients to take at all. Cost: at least $8,000 a year. * Drug: Aerosol Pentamidine

Target: (PCP)

Goal of Treatment: Prophylaxis, to prevent PCP, the most common opportunistic infection in AIDS patients

For Whom: Those who have had a bout of PCP and a T-cell count lower than 200

Shortcomings: Cost: About $3,600 a year * Drug: Ganciclovir

Target: Cytomegalovirus (CMV)

Goal of Treatment: Prevent or slow CMV-induced blindness

For Whom: Any patient with CMV retinitis

Shortcomings: Cannot be taken with AZT. Studies of the drug did not involve placebos, so effectiveness is still unclear. Cost: About $8,000 a year. * Drug: Erythropoietin

Target: Kidney; red blood cell production

Goal of Treatment: Prevent severe blood anemia

For Whom: Those with severe anemia associated with AIDS or AZT treatments; those whose blood level has decreased by at least 15 percent

Shortcomings: Toxicity studies are yet to be completed.

Drug: Alpha Interferon

Target: Kaposi's sarcoma

Goal of Treatment: Block tumor growth

For Whom: Patients with Kaposi's sarcoma

Shortcomings: Side effects of fatigue, chills, headaches and some types of anemia are possible.

SOURCE: Food and Drug Administration
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