Doctors losing war on AIDS

By Tom Carter
THE WASHINGTON TIMES

Special Report

Since November, Dr. Roxanne Cox-Iyamu has seen a noticeable rise in the number of deaths among her patients at the downtown Whitman-Walker AIDS clinic.

"We used to be able to go months without seeing someone die. Now it is every few weeks," she said with a sigh. "I saw a women yesterday with four opportunistic infections. One -- mycobacterium avium -- it was the first time Iīve seen it in three or four years."

Dr. Cox-Iyamu, an infectious-disease specialist and director of the Whitman-Walker Clinic, oversees treatment of some 2,000 HIV and AIDS patients. She said her patient was experiencing total body wasting, night sweats, diarrhea and fatigue.

The patient had been on a regimen of life-saving drugs, but they were no longer effective.

Dr. Cox-Iyamu, visibly saddened, said at this stage there were few options available to help the woman and dozens of other patients for whom life-prolonging drug cocktails have failed.

The drug cocktails have produced remarkable recoveries in many AIDS patients, but they are beginning to fail in an alarming number of cases.

And that, experts say, limits the medical options for Africa and the rest of the developing world, which are being overwhelmed by the disease.

While activists, health care workers and governments recently shamed 39 pharmaceutical companies into an agreement to provide cheap drugs to treat the 25 million people in Africa with HIV/AIDS, access to drugs is not the end of the problem.

"The drugs are needed, and they will do a lot of good," said Dr. Ronald Gray, an epidemiologist at the Johns Hopkins School of Public Health with 10 yearsī experience in Uganda. "But, if this is not done properly, we are sitting on a powder keg . . .

"There is no infrastructure to deliver the care, and the nature of this complicated drug regime means that we will see treatment failure and drug resistance. Drug resistance could wipe out the utility of these drugs in just a few years." He said if drug resistance follows the historical course of tuberculosis and malaria, AIDS in Africa could become resistant to available drugs in one year, followed by massive resistance within five years.

"Iīm not by nature pessimistic -- but I am a realist, and I am concerned," he said.

At an international AIDS conference in Vancouver in 1996, scientists introduced new "drug cocktails" of protease inhibitors and anti-retroviral drugs that prevent the AIDS virus from reproducing.

After a short time on the therapy, immune systems of even the sickest AIDS patients rebounded and the virus dropped to undetectable levels in the blood.

Misplaced optimism

Optimism ran wild. Serious scientists talked of either finding a cure for the deadly disease, or long-term management of the illness as with diabetes.

Thousands of AIDS patients, literally on their death beds, like Lazarus, got up and walked, returning to relative health and a normal life.

The complicated drug therapy requires as many as 30 pills a day, each taken at different times -- some to be swallowed with food, some without, some with water, some without. And, within six months of the introduction of the drugs in the United States, the mortality rates for AIDS plummeted -- from 40,000 a year in 1996 to just 16,000 in 1999.

But five years later, at the Seventh Conference on Retroviruses and Opportunistic Infections in Chicago in January, the optimism had diminished.

The highly toxic drugs were failing in as much as 50 percent of the infected population. In addition, even where the medication continued to work, it was causing severe side effects, including high cholesterol, liver damage, kidney stones, diabetes and osteoporosis.

One of the most appalling side effects, called lipodistrophy, or body fat redistribution, creates grotesque buffalo humps, distended bellies, sunken cheeks and bone-thin arms and legs.

The AIDS virus was also adapting, mutating into drug-resistant strains immune to some or all the drugs available.

AIDS researchers at the Infectious Disease Division of the University of North Carolina at Chapel Hill found that up to 28 percent of new HIV infections exhibit some level of drug resistance. A British study released in early May came to a similar conclusion, finding that 25 percent to 27 percent of new AIDS infections were drug resistant.

Dr. Anthony Fauci of the National Institute of Allergy and Infectious Diseases dismissed those figures, saying that resistant disease is showing up in about 15 percent of new cases -- still an alarmingly high number.

Hope fades

"The mood in Chicago was reserved resignation. We realized it is going to be a long hard slog," said Dr. William Powderly of Washington University in St. Louis, who investigates side effects of AIDS drugs.

"Three or four years ago, we thought we had turned the corner -- that was wrong. . . . We are starting to see major AIDS infections in our hospital, and we donīt have much in the way of (treatment) options."

Today, many AIDS patients, fed up with the toxic side effects and the grueling pill-taking regime, have stopped taking the drugs altogether.

"I know more people not taking the drugs now than taking them," said Michael Petrelis, a co-founder of the AIDS activist organization ACT UP, by telephone from San Francisco. "Iīm not taking them anymore. I only take medicine now to fight specific, opportunistic infections. . . . We are scared, really scared."

A. Cornelius Baker, executive director of the Whitman-Walker Clinic, tried to put the best face on the current trend.

"It is a melancholy, bittersweet time. Part of our job is to give people hope, to help them grab onto life, but all of the horror around the epidemic is not behind us," he said.

With some 22 million people dead and 36 million in the world infected, the drug therapies that held such promise five years ago, have clearly lost much of their sheen.

Drug resistance grows

"We can stop the virus from being produced in at least half the people being treated. In half, it isnīt successful, and those people will develop resistant virus," said Dr. Powderly of Washington University.

Dr. Fauci said in an interview that the therapy administered to "naive" patients -- that is individuals who have never been on any of the drug cocktails -- initially work as often as 85 percent of the time if the patient adheres to the treatment and is monitored.

Over time the efficacy rate may taper off to about 60 percent, he said.

The drug cocktails do not work as well in patients who have weakened immune systems and a built-up resistance after years of inadequate drug therapy.

In effect, that creates two populations of HIV carriers -- the newly infected, who have a number of medical avenues, and the currently infected, who have far fewer options.

Dr. Fauci, while seeing the glass half-full, nevertheless called the downside of the drug regimes "sobering."

"This is a deadly disease, and these are not perfect drugs. But the people who are saying things are all bad should have been with me 20 years ago when everybody who walked in the door died," he said. "Iīd rather have a situation where some people have difficulties with the drugs but a substantial portion of the people are doing well and living healthy lives rather than everyone who comes in the door dies."

Within days of a single human immunodeficiency virus (HIV) entering the body, most commonly through sexual relations or by using shared needles to inject drugs, the virus hides, building multiple reservoirs throughout the body. At the same time, the virus attaches to and enters healthy cells to begin reproducing.

The anti-retroviral drugs block the creation of certain proteins required for the virus to reproduce, and thereby slow the advance of the disease. In the early days, physicians directed patients to hit the infection hard with a barrage of drugs and hit it early, before the immune system showed outward signs of weakness.

Today, the official guidelines on therapy are considerably more cautious and conservative. Patients do not begin the drug therapy until the viral count has mushroomed and the immune cell count has dropped. And it is often a regime of a period of time on the drugs, followed by a respite or interruption, off the drugs.

Within three weeks of stopping the drugs, HIV emerges from its hidden reservoirs to begin attacking the body again. When HIV begins to overpower the immune system, the patient develops AIDS.

"It is a war, and the immune system wins most of the battles, but eventually HIV wins the war," said Dr. Mark Dybul, at the National Institutes of Health in Bethesda. Dr. Dybul is running "interrupted" therapy clinical trials to cut the drugs and their cumulative toxicity by 50 percent. He said he does not expect science to find a cure, but rather hopes to make the disease a long-term, manageable health care problem.

"No one dies from HIV, but after a while the immune system is so weakened, it can be overcome by opportunistic infections," he said.

Soaring infection rates

While the United States, which has between 600,000 and 900,000 people with HIV, has been able to slow the rate of new infections to about 40,000 a year. The HIV/AIDS rate is skyrocketing in the rest of the world. Africa is home to 25 million of the worldīs 36 million AIDS sufferers. It is estimated that 16,000 people a day contract the disease worldwide.

"We see 40 to 50 new cases a week," said Dr. Cox-Iyamu of the Whitman-Walker Clinic. She said it is estimated that one in 20 adults in Washington are HIV positive, many without knowing it. A most alarming trend is the rising rate of infection among young homosexual men.

"There is a sense that because people arenīt dying, AIDS has gone away," said Dr. Powderly, who also heads the HIV Medicine Association, a network of 2,000 AIDS doctors. "There is no cure. It is so incredibly naive, so stupid. It is a major societal disaster.

"More and more young men are getting HIV. They think its not a big deal; they can take the drugs. Getting AIDS is still a big, big deal," he said.

And unlike other diseases that generally strike the young and the old, AIDS hits the 15-year-old to 45-year old age group -- the parents, societal leadership, and economic breadwinners, creating 13 million orphans in Africa.

With the April agreement by the worldīs top drug companies to provide inexpensive drugs to Africa and the rest of developing world, access to the life-prolonging drugs will become less difficult. But U.S. AIDS researchers caution that while drug availability is a necessary first step, just providing cheap or free drugs creates its own set of problems.

Africa has little or no health care infrastructure, and while the drugs have been made more "user friendly," the therapy is still extremely difficult to follow. The side effects are real, and the risk of creating resistant virus strains in Africa enormous.

"Even if you make all the drugs available . . . the health care infrastructure in Africa is very poor. In fact it is minimal if not absent in many countries," said Dr. Fauci, who just returned from a trip to Uganda. "Just parachuting anti-retrovirals into a country is not going to stop the (AIDS epidemic)."

An expensive battle

By some estimates it will take at least $10 billion a year in a "Marshall Plan" to save Africa from AIDS.

Harvard economist Jeffrey Sachs, along with 127 other members of the Harvard faculty, has proposed one plan for tackling AIDS in Africa.

To initially help 1 million of the 25 million AIDS sufferers in Africa, Mr. Sachs estimates it would cost $1.1 billion the first year, growing to about $7 billion or $8 billion a year by the year 2006.

The Sachs plan calls for the United States to provide one-third of the amount.

Currently, the U.S. foreign aid budget is about $7 billion, with $4 billion earmarked for Israel and Egypt. Less than $200 million of that goes to Africa. The Harvard plan would boost U.S. funding almost 10 times, to $1.5 billion a year for AIDS.

In late April, U.N. Secretary-General Kofi Annan, told conferences in Africa and the United States that $7 billion to $10 billion a year is needed from governments and private sources to wage an effective campaign against the modern plague. He said current spending on AIDS research and prevention in developing countries is about $1 billion a year.

Mr. Annan said the United Nations should take the lead in coordinating the global battle against AIDS. He said strategy is to be addressed in a special session of the General Assembly on AIDS starting June 25.

The topic is to be continued at the meeting of the Group of Seven -- the United States, Britain, Canada, France, Germany, Italy and Japan -- in Genoa, Italy, in July.

Global fund sought

"What I propose is a global fund dedicated to the battle against HIV, AIDS and other diseases," Mr. Annan told philanthropists in Philadelphia April 30.

On Friday, President Bush pledged $200 million for the fund. Secretary of State Colin Powell, who in his confirmation hearings called AIDS a national security problem, will travel to Africa at the end of the month to get a first-hand view of the pandemic.

While the drugs are less than perfect, Dr. Fauci was adamant that the world needs to face the problem.

"If we donīt make the right choices and deal with this in a comprehensive manner, I think you will see nations disintegrate, countries fall . . . We need to give them the drugs, but to just be pouring in drugs into a country wonīt solve their AIDS problem," he said.

Dr. Powderly, who has 15 years of research and treating AIDS, said that while there has been a cure for tuberculosis for 30 years, TB rates and resistant TB rates are at their highest point in years.

"It is totally naive to think that just providing the drugs to Africa, in the absence of monitoring and infrastructure, will work," he said. "The good news is that it is actually hard to get HIV. That gives us an opportunity to help people not get infected."

Word that the worldīs rich nations were prepared to contribute to a global fund to fight AIDS, malaria, TB and other infectious diseases came out of the World Bank and International Monetary Fund meetings in Washington April 30.

Reluctance to help

But it may be naive to think that Americans will support a massive infusion of aid to deal with AIDS worldwide.

A recent survey conducted by the Christian charity World Vision found that while Americans are aware of the international pandemic, they are unlikely to support more government aid to deal with the crisis. According to the survey, 61 percent of Americans are not inclined to help overseas AIDS victims, and 54 percent are not even inclined to help AIDS orphans.

"The overall poll results are alarming, especially considering the AIDS epidemic is literally ripping the fabric of society in many African nations," said Richard Stearns, World Vision president. Whether AIDS is automatically a terminal disease depends on how the disease is viewed.

"Is AIDS a death sentence? No. With the drugs we have now, I think it is a manageable, long-term health problem," said Dr. Powderly. But for people who carry the virus, every day can be a roller coaster between hope and despair.

"I still consider this a death sentence," said Mr. Baker of the Whitman-Walker Clinic. "Iīm turning 40 this year and there is never a time when you donīt feel death is just around the corner."

Hoping for a breakthrough

Mr. Baker, who has been HIV positive for several years, said that a truncated life of pill taking and toxic side effects is not enough.

"Where is the cure? Where is the vaccine?" he asked. "Tell the (AIDS researchers) 'Donīt go home. Stay late. Donīt take vacations. Find the cure. Find a vaccine.īīī

Dr. Cox-Iyamu said there is little hope for a cure, and she is not counting on a vaccine. In the meantime, she is resigned to working with the drugs that are available.

"When we first got the retroviral drugs, we saw a lot of success, and many people are still responding well, but others developed resistance or couldnīt take the side effects," she said. "As we use up the available medicines and there arenīt new ones on the horizon, the viral loads have gone back up. People are getting sick. A couple of new drugs may be available by next summer, but that will be too late for some."

Sitting in her office, decorated with pictures of her teen-age children, Dr. Cox-Iyamu said she fears for their lives.

"I am afraid for our youth," she said. "How do I defend my kids? I can only hope and pray that I have given them the proper moral code to protect themselves."

-- Anonymous, May 14, 2001