The Wall Street Journal - Monday, February 1, 1999
Elyse Tanouye, Staff Reporter of The Wall Street Journal

Her doctor, Michael Saag, director of the AIDS clinic at the University of Alabama at Birmingham, immediately put her on powerful combinations of AIDS drugs, including the then-experimental protease inhibitors. Like so many other patients, she saw the HIV in her blood drop to undetectable levels, and she remained in good health for two years.

But last year, the virus came roaring back. Since then she has battled infection after infection, including three bouts of pneumonia. And now doctors say she's an example of a devastating new development in the fight against AIDS: "late failures" who responded well to the new drug therapies and then suddenly stopped responding.

Dr. Saag, who was one of the first doctors in the world to use the new drugs and witness their awesome power in subduing HIV, is both baffled and alarmed. Over the past year, he has observed many patients like Rabbi Culpeper.

"We're seeing a lot of people who have resistant virus; for whatever reason, their viral load is up and we can't get it back down," he says. "People who lost control go in a downward spiral and ultimately die. They just waste away and die." Dr. Saag estimates that half of his patients who previously did well on the drugs are seeing the virus return.

'Impressive Enemy'

Scott Hammer, chief of infectious diseases at Columbia Presbyterian medical center in New York, says the virus is returning in some of his patients whose viruses were previously undetectable using the most sensitive of tests. In San Francisco, Donald Abrams, another top AIDS doctor, says he has some patients who have responded to the drugs for up to three years and are "now starting to have changes in their numbers" of virus copies in their blood samples. "No one presumes the drugs will work forever," Dr. Abrams says. "The virus has always been a very impressive enemy."

At an AIDS conference in Chicago this week, researchers are expected to report disheartening findings from Merck & Co.'s long-running trial of a regimen including its drug Crixivan. According to the research, the percentage of patients with very low levels of virus copies in their blood has dropped to about two-thirds after three years from 90% early in the study.

Some researchers maintain that late failures represent a small fraction of the large numbers of patients who have generally done well on the drug. Moreover, they believe patients who succeed in driving the virus down to very low levels usually don't fail if they continue to take their medicines religiously.

Rabbi Culpeper, a tall, thin woman with a dry sense of humor, says she initially missed a few midday doses of medicines, in part because she was hiding her condition and pill-taking. But now, she seems the model patient. During a recent clinic checkup, she laughs as Dr. Saag sprinkles Yiddish words onto a page of her 3-inch-thick medical chart -- Volume III of her clinic record. When the visit is completed, she changes the paper on the examining table as she chats with Dr. Saag. "You can tell she's a former nurse," he says.

Rabbi Culpeper worked as an operating-room nurse in her native San Francisco during summer and winter breaks while attending the Jewish Theological Seminary in New York City. During one of those stints, she was accidentally stuck with a needle. It was Jan. 14, 1994: "Certain dates are seared into my memory," she says. She was immediately tested for HIV infection, and she was retested six months later. Both tests were negative.

By August 1995, Rabbi Culpeper had completed her rabbinical studies and begun working at a synagogue in Montgomery, Ala. After two months, she noticed her throat felt sore and yeasty. Her new job required a lot of speaking and singing, and she thought she just wasn't using her voice properly.

Oral Thrush

But a check by her doctor found she had oral thrush, an unusual infection among the healthy but common in people with immune deficiencies. An HIV test, to her disbelief, this time came back positive. At first she thought, "Here in Alabama they don't know what they're doing," and she insisted on a second test by an infectious-disease specialist. Two weeks later, that test result was positive.

She began preparations to resign her pulpit and return to San Francisco for treatment, but friends at the San Francisco hospital where she worked referred her to Dr. Saag's clinic, just two hours away in Birmingham. "My doctor's first words to me when I came here in tears was, 'This can be a chronic, manageable disease,' " she says. "I live by those words."

Dr. Saag right away put her on AZT, 3TC, and Crixivan, which was still in clinical trials. "Ironically, I was getting better AIDS care in Alabama than I would have in San Francisco and New York," she says. Some of her friends in those cities were waiting in lotteries for Crixivan.

The drugs initially worked powerfully against the virus. Before the drug therapy, she had 160,000 virus copies per blood sample; after a month of taking the drug cocktail, the number fell to 1,900. About a year ago, her virus count dropped to undetectable levels.

But she paid a high price -- debilitating side effects that included kidney stones, rashes, pain and diarrhea. At times when she was immobilized by the side effects, she thought, "This type of life isn't worth living." Still, her health was relatively good until about a year ago when the virus "broke through" and began proliferating.

Today, nearly out of options, Rabbi Culpeper is playing a grim waiting game, hoping to avoid serious opportunistic infections before new drugs come out. She regularly checks the clinic bulletin board to see if there's anything new among the 40 to 60 ongoing clinical trials. One experimental drug, called T-20, looks promising because it aims to gum up the mechanisms the HIV virus uses to enter patients' cells. But Rabbi Culpeper says she is trying to hold out until another version, dubbed by Dr. Saag as "son of T-20," is available.

Some of Dr. Saag's other patients haven't been able to hang on. One, Atlanta realtor Ben Davis, was the first person ever to try Merck's Crixivan. Before taking Crixivan in August 1993, Mr. Davis's virus count was one million per sample of blood, and he would have died within a year, Dr. Saag says. Within the first two months of Crixivan therapy, Mr. Davis's viral load dropped to 1,000 virus copies per sample.

By October, "everyone was very excited," Dr. Saag recalls. "It was the first time I thought of the word 'cure.' " But a month later his viral load began to creep back up, and it was clear by January that the drug wasn't working as well as it had. He died last April.

So many others among Dr. Saag's AIDS patients died around the same time that Jan Fuller, a clinic nurse, asked Dr. Saag to reinstate grief counseling, a service that had been discontinued a few years ago after patients began doing well on the new drug regimens. "A lot of our buddies died -- my heart broke," says Ms. Fuller.

Too Effective?

Dr. Saag and his staff struggle to understand why the virus is returning in some patients. Are some patients dropping their strict drug-therapy regimens? Are the low levels of virus that remain in the body despite intense drug therapy continuing to replicate, producing mutant versions that defy treatment and proliferate? One new theory is that the drug therapy, ironically, may be so effective at driving the virus down that the immune system thinks the threat is gone and halts its attack.

Along with theories, there are provocative experimental strategies. One involves taking patients off the drugs for a while to allow virus levels to rise just enough to spark a reaction by the immune system. Other tests will look at giving patients an HIV vaccine after initial drug therapy drives the virus down -- and then seeing whether the immune system can control the remaining viruses.

Rabbi Culpeper and other patients in her position are benefiting from the race to find new therapies. But the looming question for the rabbi is whether the new treatments will arrive in time. "Yes, I do think they will come up with something," she says. "I continue to make plans as if AIDS for me and everyone is a chronic, manageable disease. But it doesn't feel that way now."

990201
WJ990201

Copyright © 1999 - The Wall Street Journal. Reproduction of this article (other than one copy for personal reference) must be cleared through the WSJ Permissions Desk.

Always watch for outdated information. This article first appeared in 1999. 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, 1999. 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. .