Surviving AIDS, but still at risk

Medications that prolong life also present increased dangers

By MARILYNN MARCHIONE
mmarchione@journalsentinel.com

Posted: March 7, 2004

You probably won't see them on reality TV shows, but they are true survivors - people who have been on AIDS drugs for nearly 20 years and are successfully living with an incurable disease.

<% If Request.ServerVariables("REMOTE_ADDR") = "207.170.16.6" Then %><% End If %><% If Request.ServerVariables("REMOTE_ADDR") = "207.170.16.6" Then %><% End If %>Treating AIDS Photo/Journal Sentinel files Ralph Chrisman (right) meets with his doctor, Ian Gilson. The 56-year-old Milwaukee man was diagnosed with HIV in 1986, and he credits his medication for his survival. "I would be dead without those drugs," he says. Quotable HIV is really becoming managed so we're dealing with more traditional health risks. - David Fisk, medical director of the AIDS Resource Center Related Story Doctors: Protest higher cost for AIDS drug

New research shows the highs and lows of what life is like for them - increased risks of diabetes and other problems, but also that they are living long enough to acquire typical diseases of aging, such as cancer.

"HIV is really becoming managed so we're dealing with more traditional health risks," along with side effects that are becoming more common as more people spend decades on the drugs, said David Fisk, an assistant professor at the Medical College of Wisconsin and medical director of the AIDS Resource Center of Wisconsin.

Ralph Chrisman is an example.

The 56-year-old Milwaukee man started on AIDS medications soon after he was diagnosed with HIV in 1986, and he is well enough now to work a couple of hours a day.

"I would be dead without those drugs," he said, even though he now also needs Lipitor for high cholesterol and other medications for diabetes - problems he developed after starting AIDS treatment.

It's been almost two decades since the first AIDS drug, AZT, came on the market, and a decade since powerful drugs called protease inhibitors became available - enough time for their long-term effects to start to become apparent.

Although the drugs have allowed hundreds of thousands of HIV-infected Americans to live relatively normal lives, research suggests that taking them for many years can cause side effects that eventually catch up with many people.

Studies presented recently at the 11th annual Retrovirus Conference, a meeting of AIDS researchers in San Francisco, show that people taking AIDS drugs were more likely to develop pre-diabetes or diabetes. They also developed certain kinds of cancer, including Hodgkin's disease and lung cancer, at higher rates and at earlier ages than the general population.

"These medications are not without long-term consequences," said Karen Ivantic-Doucette, a nurse at Aurora Healthcare's Positive Health Clinic, which treats about 350 AIDS patients. And if patients have any underlying risk factors for heart disease or diabetes such as obesity when they start on the drugs, "these will make it worse," she said.

Determining which side effects are linked to AIDS drugs or to the disease itself has always been difficult. Most people who test positive for HIV go on treatment, and in the U.S. there isn't a large group of untreated HIV-positive patients to compare them with.

Drugs may directly cause some side effects or they may magnify problems that actually are caused by HIV or that were there before the patient caught the virus, such as a genetic predisposition to heart disease.

Some side effects appeared soon after certain drugs or classes of drugs were introduced. For example, protease inhibitors have been linked to risk factors for heart disease such as high cholesterol, abnormal body fat distributions and metabolic changes. Other drugs have been linked to specific neurological problems.

Sometimes patients can be switched to a different drug or combination. Or their side effects can be managed, such as giving a statin drug to control cholesterol.

But when those conditions lead to more permanent or serious long-term problems, such as diabetes, they generate a new level of concern.

"To me, that's very serious," Ivantic-Doucette said, especially for people who have a family risk for the disease. For them, the AIDS drugs become "an independent trigger added to a genetic trigger," she said.

Drugs, risk appear linked

The largest study to examine the issue gives reason for concern.

It involved more than 1,100 men in the Multicenter AIDS Cohort Study, a federally funded study based at Johns Hopkins University in Baltimore. Half of the men in the study had HIV, and the rest were an HIV-negative control group matched for age and other characteristics.

After three years, those on AIDS drugs were three times more likely to develop diabetes or hyperglycemia, a blood-sugar condition often called pre-diabetes.

The type of drug they were on made a difference. The risk was twice as high for those on protease inhibitors or the drug d4T, and four times higher for those on efavirenz, sold as Sustiva.

"Sustiva is considered the preferred drug for initial therapy. It's like water around here," Fisk said of the clinic he directs at the AIDS Resource Center.

Another study reported at the San Francisco conference looked at cancer rates for those with AIDS. It was done by doctors in Chicago and at the Centers for Disease Control and Prevention in Atlanta.

They compared cancer rates in nearly 8,000 patients at two Chicago HIV clinics with millions of Cook County and Illinois cancer registry patients. They also compared rates for 4,000 patients in the study who didn't live in Chicago with millions of patients in a federal cancer registry. Results were adjusted for factors such as age and whether people smoked.

Several cancers have long been known to be more common in people with AIDS, such as cervical cancer, Kaposi's sarcoma and non-Hodgkin's lymphoma.

Some cancers not considered related to AIDS - lung, Hodgkin's disease, melanoma, and head or neck cancers - were significantly higher among those on AIDS drugs. Rates ranged from two times higher for lung cancer to 77 times higher for Hodgkin's disease.

However, the risk for other common cancers - breast, prostate and colon - were not higher among AIDS patients.

Long-term effects

A third study raised potential concern about what happens over the long term when AIDS drugs don't fully control the disease, or when patients aren't treated.

AIDS-related dementia used to be a common debilitating complication of HIV, and AIDS drugs have dramatically reduced it, but there's been concern that less severe cognitive impairment still might be going on.

Researchers from several California hospitals and universities reported evidence that some patients on AIDS drugs, especially those with detectable amounts ofHIV in their blood, have ongoing brain damage.

Doctors did MRI and other neurological tests on about 60 HIV patients and about the same number of matched controls, adjusting for how much alcohol they regularly consume, which affects brain function and health.

People on AIDS drugs had greater ongoing loss of white matter, the infrastructure of the brain that carries nerve impulses that originate in the gray matter. Those with significantly detectable virus had more ongoing white matter loss, and those with no detectable virus in their blood had the same white matter status as the control group of people without HIV.

The rates of white matter atrophy were small and didn't cause cognitive impairment, but "it is possible that the cumulative effects of ongoing brain damage may produce such impairments in the future," the researchers warned.

There was some good news.

A study of more than 8,300 HIV patients in the U.S., Europe and Australia showed that developing high blood pressure was due to traditional risk factors - being older, male or overweight.

"They did not find a specific association with HIV drugs," as had been feared, said Constance Benson, a University of Colorado AIDS expert who was not connected with the study. "The conventional risk factors were much more important."