AIDS researchers don't like to admit that the field is in a slump, but it is hard to escape that conclusion.
There have been no major breakthroughs since the development of protease inhibitors six years ago. Many patients have stopped taking anti-AIDS drugs because of a growing incidence of both side effects and resistance to the drugs by the AIDS virus. And people continue to be infected at a rate that hasn't changed for a decade.
Clearly, any better control of the AIDS epidemic is going to take a lot longer than scientists had expected or predicted even a few years ago.
Nowhere was this more apparent than at the ninth annual Retrovirus Conference in Seattle last month. Although researchers reported glimmers of hope in several new approaches to AIDS drugs, it will require years of hard work before any of those hopes are realized.
"It's becoming more and more difficult to make a major breakthrough" in AIDS research, said Dr. Raymond Schinazi of Emory University in Atlanta. "All the easy stuff has already been done."
Progress in the last two or three years has been "absolutely glacial," said Lee Klosinski, director of programs for AIDS Project Los Angeles.
"We weren't expecting a great deal this year, and we didn't get it," added Dr. Harvey A. Elder of Loma Linda University Medical Center.
And while the pace of research has seemingly slowed, the progress of the epidemic has not. Therapeutic advances have slashed the U.S. AIDS death rate from 40,000 per year to 15,000, but the number of new infections has held steady at about 40,000 per year. As a consequence, almost 1 million Americans are living with an HIV infection, according to new estimates from the federal Centers for Disease Control and Prevention.
And as people are spending longer times taking AIDS drugs, new complications are becoming apparent. Foremost among them are a number of side effects caused by the drugs themselves, ranging from simple nausea and lethargy to abnormal fat distribution on the body, high cholesterol levels, diabetes and now, new research suggests, an increased risk of heart attacks.
The side effects can be so severe that many patients are abandoning therapy, with disastrous consequences. New data show that those who quit taking drugs are much more likely to develop AIDS or to die.
Meanwhile, those who are doing well on the drugs are also facing some new problems that they didn't expect.
Particularly alarming to physicians at the recent meeting is the growing incidence of liver disease caused by co-infection by the hepatitis B and C viruses.
"We're becoming liver doctors as much as anything else," said Dr. David Stone, an AIDS treatment specialist at Lemuel Shattuck Hospital in Boston. "Fifty percent of our patients' deaths since 1999 have been from liver disease."
"In the past, these patients didn't live long enough for their hepatitis infections to become a problem," added Elder. "Now we have to treat for both HIV and hepatitis."
Protease Inhibitors' Side Effects Puzzle Doctors
There has been a gross change in researchers' mood since the introduction of protease inhibitors six years ago. Their powerful antiviral effect led scientists to hope that we were on the road to controlling the AIDS epidemic.
But the side effects of the drugs and the growing resistance of the virus to therapy have dampened enthusiasm.
Many of the side effects of therapy have been attributed to the protease inhibitors specifically, especially increases in cholesterol levels and dysfunctions in fat metabolism. Now, possibly as a result of those changes in lipid metabolism, the drugs are also being linked to heart attacks.
Dr. Scott Holmberg and his colleagues at the CDC in Atlanta studied 5,675 HIV-positive people in eight cities, half of whom were taking protease inhibitors. Heart attacks were rare in this group, probably because the patients were relatively young.
Nonetheless, there were 13 heart attacks among those taking protease inhibitors, compared with only two among the patients not taking the drugs--a more than fivefold increase in risk.
"It would be unusual to see relative risk ratios like that" unless the drugs were causing it, Holmberg said. "We think we are seeing an early but still relatively small problem."
A study at UC San Diego called those results into question, however.
Dr. Samuel Bozette and his colleagues examined the records of 36,766 HIV-positive veterans over the same time period covered by the CDC study and found no increase in heart attacks among those taking protease inhibitors.
"This complication [heart attacks] does not seem to be changing," Bozette said.
It is not clear which study is correct, noted Dr. Harold Jaffe, who is in charge of AIDS programs at CDC, adding that more research is needed.