Drug Resistance Complicates HIV Therapy
At least one in every four San Franciscans newly infected with HIV, the virus that causes AIDS, contracts a form that is resistant to one or more of the commonly used AIDS drugs, researchers said here Saturday.
As a result of this resistance, it takes at least three times as long to bring these infections under control, and more complicated drug regimens are often required, said Dr. Frederick M. Hecht of UC San Francisco.
Hecht’s remarks came on the eve of the 14th International AIDS Conference, which opens in this Mediterranean port city today. The findings are particularly alarming with respect to HIV treatment in developing countries, because the greatest increase in resistance was observed for the drugs that are least expensive--and thus more likely to be widely used in the Third World, other experts said.
In a separate study, Baltimore researchers found that, contrary to the belief of many physicians, HIV infections can be safely treated in people who are also infected with the hepatitis C virus.
Some scientists had thought that the AIDS drugs would exacerbate liver problems caused by the hepatitis, but that was not the case, Dr. Richard E. Chaisson of the Johns Hopkins University School of Medicine said. In fact, the hepatitis victims in the Baltimore study who were not treated for HIV developed AIDS and died sooner than those who were treated.
Virtually all HIV-positive people should receive anti-AIDS drugs, even if they are also infected with the hepatitis C virus, Chaisson concluded.
Both sets of findings appear in the July 10 Journal of the American Medical Assn.
San Francisco is an ideal place to study transmission of resistant strains of HIV because many AIDS drugs receive their first trials there, antiviral therapy is widely used, and increases in high-risk behavior among its young male homosexuals have meant greater AIDS transmission, Hecht said. Trends that appear in San Francisco are likely to appear elsewhere a few months or years later.
Hecht, Dr. Robert Grant and their colleagues studied 225 newly infected patients--none of whom had yet received treatment--between 1995 and 2001, using at least two different tests to determine drug resistance. Their criteria were quite stringent, requiring that a resistant virus tolerate 10 times the normal dose of a drug.
They found that about 25% of the patients had a virus resistant to reverse transcriptase inhibitors--the first and most widely used class of AIDS drugs--in 1996 but that the incidence of resistance had dropped to 7% in 1998-99, probably because of the increasing use of other drugs during the period. By 2001, however, the rate of resistance in this class resurged, to 21%.
Equally alarming was the growth of resistance to the non-nucleoside reverse transcriptase inhibitors, a new and potent class of drugs. The team found no resistance to the drugs in 1996, when they had just been introduced. But resistance levels grew to 6% in 1998-99 and 13% in 2001.
These two classes are the most likely to be used in developing countries because they are the cheapest.
For the final class of drugs, protease inhibitors, the resistance rate was 3% at the beginning of the study, 5% in 1998-99 and 7% in 2001. Hecht speculates that either the drugs in this class impair transmission or the resistant virus is somehow less viable.
The percentage of patients with resistance to more than one drug had climbed to 13% by 2001.
“Fortunately, only one of the 225 subjects was resistant to all three classes of drugs,” Hecht said.
Overall, 27.4% of the patients in 2001 had a virus resistant to at least one drug.
The patients with resistant viruses could receive effective treatment, but it was more difficult, Hecht said. For those without resistant viruses, four weeks of treatment were required to reduce the virus to undetectable levels in the blood. For those with a resistant virus, 12 weeks were required.
The researchers also expect the incidence of resistance to continue to grow in the near future.
“The question,” Hecht said, “is whether it will eventually plateau or keep growing.”
The take-home message, he concluded, is that people who engage in high-risk behaviors are now putting themselves in a position to contract a form of disease that is increasingly difficult to treat.
Hepatitis C infections are a major problem among the HIV-positive because the two viruses are spread in the same way: by intravenous drug abuse and unsafe sex. In the United States and Europe, one in every three HIV-infected people is also infected with hepatitis C, according to Dr. Glen R. Hanson, acting director of the National Institute on Drug Abuse. In some cities, more than half of HIV-infected people are co-infected.
But what to do about this has remained problematic. Some small studies had suggested that the AIDS drugs accelerated the pace of liver disease. A majority of those with both viruses, furthermore, are injection drug users, and some clinicians doubted that they would adhere to treatment regimens. As a consequence, many patients have gone untreated.
Chaisson, Dr. Mark Sulkowski and their colleagues studied 1,995 HIV-positive patients who visited HIV clinics at Hopkins between 1995 and 2001. None had AIDS, but 45% were co-infected with hepatitis C. The patients were treated by other doctors in the routine course of business. The team merely monitored the outcomes.
The team found that those with the hepatitis C virus responded as well to AIDS therapy as did those without the virus. The Hopkins clinicians gave AIDS drugs to 69% of those who were not infected by the hepatitis C virus and to 54% of those who were. And those who did not receive the drugs progressed to AIDS and died sooner.
The bottom line, Chaisson said, is that physicians should treat patients who are co-infected in the same manner they would those who do not have hepatitis C.
But he and others cautioned that treatment of hepatitis C simultaneously with AIDS treatment can, in fact, cause serious liver problems. If physicians intend to treat the hepatitis, they should do it before beginning AIDS therapy.
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Maugh is on assignment in Barcelona.
