By Jeff Balke
By Aaron Reiss
By Angelica Leicht
By Dianna Wray
By Aaron Reiss
By Camilo Smith
By Craig Malisow
By Jeff Balke
Sitting at a table in his bright, sunny new apartment, John Termine invites a visitor to check out his pills. He does this as casually as if he were asking if anyone wanted a beer. They're in the kitchen, he says. In the breadbox.
Inside the white plastic box, there isn't room for even a slice of bread. Instead, Termine has crammed it full of bottle after bottle of prescription drugs and vitamins. It's a dizzying display. In one day, John Termine has to swallow about 50 pills. Some are tiny tablets, others as big as the top of a pinkie finger.
"I used to have some real colorful ones, orange ones," he says almost wistfully as he opens one bottle. "Now they're mostly beige."
They have futuristic-sounding names like Agenerase and Viriad and Vicadex AC. Termine takes them to combat the HIV that has been living inside his body since at least 1987. Seventeen of the pills are supposed to attack the virus; the rest are vitamin and mineral supplements he hopes will enhance his health.
A native of St. Louis and a hair stylist (although lately he has not been feeling well enough to work), Termine lives with his longtime partner, Brett, who is HIV-negative. Although once on Medicaid, Termine is fortunate enough to be covered by Brett's medical insurance, which pays for his pills. The average yearly cost for HIV drugs for a patient is around $20,000. But unfortunately for Termine, many of the prescription pills in the 39-year-old's collection have stopped working.
He has become resistant -- one of the biggest four-letter words in the HIV community.
"You can tell when they stop working, when your viral load goes up," he says. "You get the little skin rashes, fungus on your toenails, thrush in the mouth. You just start feeling little things pop up."
And because he has been positive for so long, he has become resistant to every single HIV medication on the market. Over the years, Termine has tried almost every drug that's become available, a number he conservatively estimates at around 40. And although his doctor has decided to keep Termine on his current regimen for now, Termine's best chance lies in the fall, when new expanded-access drugs (drugs yet to receive U.S. Food and Drug Administration approval) may become available.
Some doctors fear a supervirus, a strain of HIV that will become so powerful no drugs will be able to attack it and win. An upsurge in the number of AIDS deaths could result.
"The general public doesn't know the nuances of having to take pills and the side effects," says Termine's doctor, Shannon Schrader. "The death rate is starting to creep up, and most of us who take care of people in the community, we're seeing the number start to bump up again."
Termine's experience is what some doctors and scientists would call a perfect example of the need for HIV drug-resistance tests. Resistance tests, which appeared on the market in the mid-'90s, help clinicians determine if a patient has developed a resistance to the drugs he or she is taking. Texas's Medicaid program, which covers the largest majority of HIV-positive patients in the state, is one of only five across the country that doesn't pay for these new tests.
Termine thinks that resistance tests should be covered through Medicaid, and he wonders if he would have benefited from the tests if they'd existed when he was first diagnosed.
"I think [if we'd had the tests] we could have stretched some of my drugs out longer," he says. Without resistance tests, his doctors have had to look at his T-cell count and his viral load, and make educated guesses based on his drug history. Doctors who think the new tests should be paid for see them as a gold mine, especially considering the fact that many newly infected patients are already resistant to drugs because they have contracted a drug-resistant strain of HIV.
But not all practitioners who deal with HIV-positive clients are so quick to agree that Medicaid should pay for tests, which rarely deliver clear-cut results. Only one test on the market has received FDA approval, and some doctors consider the expensive test results difficult and confusing to read -- and say if interpreted incorrectly they could do more harm than good. These practitioners worry that the tests may become the wrong standard of care, and that public money would be better spent on reducing the number of new infections. After all, state funding for the prevention of HIV and other sexually transmitted diseases has not increased in almost ten years.
Although Termine knows the arguments, and can sympathize with both sides, right now he's got a new concern in addition to his resistance: In late May, he had several lymph nodes removed. Doctors fear some might be malignant.
"If the tests come back positive, I really have to think about what I want to do," he says. "My little body is pretty worn out."
But as quickly as he admits this, the fighter so clearly inside of this upbeat, extroverted man comes out. He hasn't given in to the virus yet, going so far as to fly to Europe for experimental treatments with human placenta and ozone. The lymph nodes might not be malignant. And as long as he can handle his resistance until there is another drug, he has a chance to extend his life a bit more.
"I don't feel hopeless," he says. "In the back of my mind, I think there's going to be something else. If I was hopeless, I would have given up a long time ago."
In the 1980s, the image of HIV was a terrifying one. If someone said "AIDS," pictures of frighteningly thin young people covered in purple Kaposi's sarcoma lesions came to mind. But with the advent of powerful protease inhibitors in the mid-'90s, the lay public developed a different picture of the dread disease. A 1996 Newsweek cover story almost giddily asked, "The End of AIDS?" Death rates fell, lives were extended, Magic Johnson declared his viral load undetectable.
The portrait of HIV became one of a chronic, manageable illness, like diabetes.
But the fanfare welcoming the new drugs masked the difficulties of taking them properly. The protease inhibitors, like all HIV medications, were expensive, had to be taken several times a day under a variety of specific circumstances and caused all sorts of short- and long-term side effects -- some serious, others merely nuisances. Numbness, diarrhea, nausea, cardiovascular illness and elevated triglyceride levels are just a few of the symptoms people such as John Termine had to accept in a trade-off for a longer life span.
"Most people who are on drugs and are HIV-positive are not very open about what they're going through," says Joel Martinez, director of The Center for AIDS, a privately funded organization in Montrose that works to educate HIV-positive people about treatment options. "People don't have the outward manifestations of the disease they once had. [But] they're not going to say, 'I've had diarrhea for six months, I'm fatigued every day.' They're not going to admit it."
In addition to the nasty side effects, fitting the drugs into a daily schedule is a task best suited for Sisyphus. Some drugs need to be taken with a gallon of water a day, some with food, others with no food. Some pills need to be refrigerated, others don't. Martinez cites studies that show even doctors and nurses often forget to finish a ten-day dose of antibiotics, yet it's expected that HIV-positive patients stick to a strict regimen for their whole lives.
So what's wrong with not complying? By not taking the drugs exactly when and how they're supposed to, HIV-positive patients increase their risk for growing resistant to them. A vicious virus, HIV reproduces rapidly inside the body. The more the virus multiplies, the greater the odds are that mutations -- changes in the virus's genes -- will appear. While some of these mutations are harmless, others are resistant to the drugs. If too many doses of the drugs are missed, the virus multiplies at a faster pace and more mutations appear, decreasing the odds that the drugs will have a beneficial effect on the body.
And as Martinez points out, even strict adherence does not necessarily mean a person will not develop resistance to certain drugs. Genetic predispositions, drug absorption problems and plain bad luck all can play a role in causing a person's HIV to develop mutations that are resistant. And as if there weren't enough to worry about, studies show an increase in the transmission of drug-resistant strains among newly infected people, especially in urban areas such as Houston, meaning that people who haven't even discovered their HIV status yet are already resistant to several drugs.
With those concerns in mind, and after urging from health care practitioners across the state, Texas's Medicaid program seems to be moving in the direction of paying for drug-resistance tests. John Hellerstedt, medical director of the Medicaid/CHIP (Children's Health Insurance Program) division, a part of the state's Health and Human Services Commission, says that Texas hasn't been unduly slow in approving the tests. It just wants to be sure the tests are worth the state's money.
"We always have to be good stewards of public funds," says Hellerstedt. "We want to make sure our policy guides people appropriately."
According to Hellerstedt, the program's medical policy committee began debating whether to pay for the tests in January, and is in the process of determining exactly what guidelines they should recommend to the senior staff of the commission. Financial impact estimates are also being drawn up. With commission approval, Medicaid may start paying for tests this summer.
There are two resistance tests available, and they are performed by a wide variety of labs across the country. Genotype tests examine the HIV virus taken from the patient, checking for certain mutations that have been linked with drug resistance. They cost $300 to $500, and doctors get the results within a few days. The more complicated phenotype tests determine which drugs can stop the virus from growing. These tests also are more expensive, costing between $700 and $1,000. Results take anywhere from two weeks to a month. At present, Texas's Medicaid program is considering paying for only genotype tests.
"I've heard that even big states have found there isn't a lot of demand for [genotype] tests," says Hellerstedt, who adds that he can't estimate what the tests might cost the state. (In Texas, Medicaid's total budget for September 1, 2001, until August 31, 2003, is $25.2 billion.)
But with the state worrying about how to pay for the drugs of indigent people (see "Getting Ugly"), and the various demands being placed on already maxed-out public funds for HIV care, The Center for AIDS' Martinez and others wonder if paying for tests is the best solution to dealing with such a complicated disease.
"I think the problem is, do we make this part of the standard of care without any kind of proof that it has a long-term effect on a person's health?" says Martinez. "Would we be better off providing greater money for ADAP [the AIDS Drug Assistance Program]? Would we be better off providing money for an ultrasensitive viral load test? There are limited resources. There is only so much money that is going to be allowed to us."
Dr. Natalie Vanek's tiny office at the Thomas Street Clinic, the largest freestanding HIV clinic in the country, is a mixture of the personal and professional. A Far Sidecalendar and Glen Campbell CDs are kept not too far from a thick booklet titled "Ninth Conference on Retroviruses and Opportunistic Infections" and a poster of colorful pills labeled "Antiretrovirals at a Glance."
Originally from a tiny north Texas town, Vanek arrived at the clinic in 1989 as a medical student. She liked it so much she never left. Now she has about 350 HIV-positive patients, all of them on public assistance.
"I like public health, and I like working with the indigent," she says brightly. "I'd rather die than work in a wound center."
Thomas Street clients are exclusively HIV-positive people who have no health insurance. John Termine was a patient at the clinic before gaining coverage through his partner. Primarily federally funded through the Ryan White CARE Act, the clinic was able to afford resistance tests only a month ago, even though private insurance companies have been paying for some of these tests for the past few years. But Vanek is not too fired up about Texas Medicaid reimbursing the cost of the tests.
"We learn as we go with HIV, and we have a lot to learn about resistance tests," she says.
Vanek's primary concern centers around the fact that there are no universally accepted standards for these tests, and it is up to the doctors to interpret the results. Unlike the tests that determine whether bacteria are resistant to a certain antibiotic, the results of HIV drug-resistance tests are often foggy.
To make her point, Vanek gives the example of a doctor wanting to know if a certain strain of bacteria is resistant to penicillin.
"If you sent [the bacteria] to the U.S. or Japan or Sweden, if you sent it all over the country, the results would be universally accepted," says Vanek. "If you got this number, there would be no debate -- it would be universally accepted as bacteria that is resistant to penicillin. But all these different companies have different [HIV resistance] tests, and they don't agree -- not even with each other. I think the companies are going to have to sit down and agree on a certain standard, but they don't want to share their proprietary information with each other."
Vanek cites a Centers for Disease Control and Prevention study where five well-known strains of HIV were sent to about 15 companies around the country for resistance testing.
"The CDC knew the strains back and forth," she says. "But there were only three companies that got it right."
While Vanek acknowledges that there are a few large companies in the United States that do trustworthy tests, she worries about what are termed "home brews," tests done by smaller regional labs that might not be as accurate but are often cheaper.
"If Medicaid is going to be paying for this, I know what Medicaid will do," she says. "They will send out bids and go with the lowest bidder, a place that may not have reputable results."
In addition, the results for most of the tests are often nebulous. The strain might be resistant, or the strain is a little resistant. If a doctor who doesn't have a lot of experience with the virus interprets the complicated results incorrectly, he or she might take the wrong course of action.
Before Medicaid agrees to spend state money on these tests, Vanek wants reassurance that the tests are of high standard and are highly reproducible (meaning the same test could be run many times by many people and the results would always be the same). While she admits there are times when running a test is a good idea (for example, on an HIV-positive pregnant woman not taking drugs who needs to start medication again), Vanek thinks the Thomas Street physicians have done "pretty good" without the tests. Instead of resistance tests, they've looked at viral load and T-cell counts, and used their deep understanding of patients' drug and health histories.
Dr. Wayne Shandera, a colleague of Vanek's at Thomas Street who has about 100 indigent HIV-positive patients, agrees with several of Vanek's points. He's especially concerned with the ability of most clinicians to read the results.
"It's poorly understood," says Shandera of the tests. "I don't understand it well, and I probably understand it better than most."
Shandera relates a recent experience that proves an attentive physician and carefully kept patient records are just as important as any resistance test. He was trying to determine which drugs to prescribe for a patient, but because he didn't have the patient's chart in front of him, he was able to work off the results of only the man's resistance test. After interpreting the results, he decided to have his nurse call the patient and change the man's medication.
"But first I told the nurse, 'Let's look up his record,' " says Shandera. "In the meantime, the chart came back and we reviewed it, and lo and behold I had had him on that medicine, and he had done worse on that medicine."
Shandera, like Vanek, would like to see the money that might be used on resistance tests spent on other programs, such as prevention, and on studies that try to discover why so many patients aren't diagnosed earlier. While the state's health department has access to the number of newly infected patients only from 1999 on, there has been a slight jump over the past three years in new infections among Hispanics. And according to Shandera, more than half the Hispanic patients diagnosed with HIV at Ben Taub already have full-blown AIDS and don't know it.
"It distresses me to see a test that will be used inappropriately -- especially in the private sphere -- when it's poorly understood, when the money on the state level could be used more effectively on prevention programs," he says.
According to Casey Blass, director of HIV and STD health resources with the state's health department, state funding for prevention "has been level since 1993." Texas spends about $27 million on prevention programs for STDs and HIV, with just over $20 million of that coming from federal funds.
But Texas is a conservative state, says Vanek.
"Nobody wants to talk about prevention in Texas, because if you want to talk about prevention, you have to talk about sex," she says. Vanek, who sees most of her new cases in minority women of childbearing age, believes that state authorities "don't realize how many young people are engaging in extremely risky behavior."
"If we're doing these tests routinely throughout the state," adds Shandera, "I fear that we're going to be faced with exorbitant costs, and we're not going to be positively changing our outcome."
When Shannon Schrader was studying to be a doctor in Kentucky in the mid '80s, he had one lecture on HIV. Medical schools just didn't talk about the disease much back then. Now, nearly 20 years later, Schrader works with about 1,000 HIV-positive patients in Houston and Harris County. Like all doctors who work with HIV, Schrader is constantly attending conferences, reading medical journals and conferring with other physicians to stay on top of the rapidly changing field. He sees indigent patients at the Montrose Clinic and has a private practice of insured patients, including John Termine.
While he acknowledges the tests are expensive, Schrader thinks Medicaid should pay for them. In the long run they might even save the state money.
"It costs more to not approve the test, because you could put someone on a regimen that they're still resistant to, and that person will develop infections and then the state will have to pay for hospitalization, et cetera," says Schrader. And whereas a genotype test can cost about $400 to perform once, keeping a patient on drugs that aren't working can cost the state several thousand dollars a month.
"I'll be honest," he adds. "In every scenario, you don't need a resistance test, because if you know the mutations as a physician and you know your patient's history, you could probably give an educated guess."
But Schrader points out that resistance testing is especially crucial among newly diagnosed patients who have yet to try any medications, and for the advanced patient like Termine where a test might discover what's left that will work.
Dr. Joseph Gathe Jr., who sees the largest number of HIV-positive patients in the Houston area (about 2,500), agrees. He estimates about 15 to 20 percent of his patients are covered through Medicaid. According to Gathe, while the tests have limitations, they will never be improved if they are not used out in the field.
"In 1994, 1995, there was a test called a viral load, which tells us how active HIV is in an individual patient's system," says Gathe. "But when the test first came out, the interpretability wasn't there and the reproducibility wasn't there. We didn't know what the test meant."
But, says Gathe, as the test was used in the medical trenches, the viral load test became better understood and more refined. Now, it's an invaluable tool for any HIV physician. According to Gathe, it's impossible to say if the resistance tests will follow this same model, but the circumstances seem similar to him.
"No matter how technology is used in somebody's laboratory, until you take that technology and put it out here in the real world to see how it fits different populations and different people, you're never going to know how good the test is," he says. "It's a complex situation, but I'm hoping [Medicaid officials] see the light and do the right thing. Without having that test, it would impair our ability to adequately take care of our patients."
Gathe agrees that if the tests are paid for by public funds, there should be certain regulations on how and when they can be ordered. And while Medicaid's Hellerstedt declined to say whether the state would pay only for tests that have been approved by the Food and Drug Administration, FDA officials are hoping their recent approval of one genotype test will help make the tests safer.
"We felt these tests were getting out there in an unregulated fashion and being introduced into interstate commerce, and we felt there needed to be standardization and uniformity," says the FDA's Andrew Dayton, who wrote the first draft of guidelines for the tests in August 2001. After about a year of review, the FDA approved the Trugene genotype test, marketed by Visible Genetics Inc., last September.
According to Dayton, it's only a matter of time before more companies try to compete with Trugene and also get approved.
"We've written the guidance documents to sort of lower the bar so it's possible to get these things cleared by a variety of different kinds of data," says Dayton. "The experts will disagree, but the key thing to remember is that we truly believe anything we clear, you're better off using it than not using it, and there's clinical data to support that."
Indeed, Visible Genetics spent six years in research and development to refine the Trugene test before it was approved, says CEO Richard Daly. And unlike home brews, Daly says, the Trugene test -- which costs around $350 -- will be easy for doctors to read. The company even promises color-coded test results: red text for resistance, amber italics for possible resistance, green for no resistance and so on.
Daly acknowledges the concerns of doctors such as Vanek and Shandera, and admits that his company's tests are just one part of treating HIV-positive patients and selecting the best drugs for them. He thinks only doctors with training in HIV should be working with HIV-positive patients. But in the end, he says, there must be room for these tests -- if they are done the right way.
"It's like what it must have been like to be a doctor who was trying to set a broken leg right after they invented the X-ray," says Daly. "Prior to that, you were wondering, 'I wonder how broken this leg really is.' And you did the best job you could. Well, this test is essentially a picture of the virus, and it allows the doctor to accurately direct the therapy. From that point of view it's incredibly cost-effective."
John Termine is in mixed spirits. The lymph nodes they removed from his body were not cancerous, but shortly after that good news, Termine learned his spleen and gall bladder were enlarged and would have to be removed. Doctors guess that their unusual growth is a side effect of long-term medication.
It's been a little over a week since the surgery to remove his two organs, and Termine is mostly resting at home, going outside a few times a day to take his two dogs for a walk. Schrader calls Termine a star patient because he does as much of his own research as he can, reading magazines for HIV-positive people and surfing on the computer, hunting down information on his condition. Ever vigilant, since the surgery he's been doing lots of fact-finding.
"I've looked everything up on the Internet," he says. "The gall bladder had so much information, but the spleen didn't have very much." He called his sister, a nurse, and she said she wasn't quite sure of the spleen's function either. But doctors have reassured Termine. He can live without it.
The kitchen is full of flower arrangements sent by friends and family. Termine almost doesn't have room for all the bouquets he received after the operation. He appreciates the good wishes, he says, although he wonders if his friends are acting too quickly.
"I'm not dying!" he says, in a good-natured voice. "It's not the funeral yet."
Termine says he was worried that going in for surgery might disrupt his pill-taking schedule. He took all of his bottles to the hospital, just in case. He was especially concerned that some pills that needed to be refrigerated would not be stored properly. So he called Schrader, who told him not to worry -- the pills could stay at room temperature for a few hours.
Sometimes Termine talks about the pills like a worried father. But there is another, more difficult dynamic at play. The pills have been a best friend and a cruel enemy. Because of the pills he has lived long enough to travel, fall in love and take his dogs for a walk this afternoon. And because of the pills he has suffered rashes, diarrhea, unexpected surgery and the jarring disappointment that comes when they just stop doing their job.
"It's a love-hate relationship," he says.
And for now, it's also a waiting game, until the fall, when he hopes Schrader will put him on a new expanded-access drug. Until then there is a life to be lived, doctor's visits to schedule and the frequent trips to the breadbox in the kitchen.
"There have been a couple of times when I just go there and stand in front of them and think, 'I cannot do this today,' " says Termine. "But then you just do it. You take them in."