BBC News 5 Jan. 2000

Medication prescribed to HIV-infected patients causes 10% of them to suffer liver damage severe enough to merit ending the treatment, researchers have found.

The problem is particularly severe among those taking the protease inhibitor, ritonavir.

Researchers from Johns Hopkins University in Baltimore, US, found that liver damage was five times more likely among patients taking ritonavir than those taking other drugs.

The scientists had expected to find that all protease inhibitors were equally toxic to the liver.

However, patients taking ritonavir accounted for half of all those with liver damage.

Lead researcher Professor Mark Sulkowski said protease inhibitors could still be used safely, but warned that doctors should monitor liver enzyme levels for signs of trouble.

He said ritonavir should be used with caution in persons with underlying liver disease.

Doctors unsure

Although protease inhibitors have been key in lengthening survival for people with HIV and delaying full-blown AIDS, some doctors have been reluctant to prescribe them because of reported side effects.

Soon after the drugs were released for public use in 1996, several case reports indicated that they could cause liver toxicity, especially in people co-infected with the hepatitis C virus.

The mechanism by which they might cause this effect is unclear, and doctors could not be sure that the drugs were really toxic.

The Hopkins researchers analysed 211 people over a two-year period who were undergoing treatment with four different protease inhibitors: ritonavir, saquinavir, indinavir and nelfinavir.

They also looked at 87 patients who were undergoing treatment with another category of anti-HIV drugs called nucleoside analogues.

Liver toxicity

Doctors periodically collected information on patients sex, age, race, social practices, drug doses and clinical variables such as new illnesses. They also monitored liver enzyme levels using blood tests.

The doctors discovered that 10% taking protease inhibitors experienced severe liver toxicity.

The risk was only slightly higher, 12%, for those with hepatitis C.

Hepatitis C-infected patients who were not taking ritonavir, however, were more than three times as likely to develop severe liver toxicity, indicating that patients with hepatitis C co-infection may be at a greater risk for medication-related liver damage.

However, Professor Sulkowski warned that excluding every patient with hepatitis C from getting protease inhibitors would deny many the chance to benefit from the drugs.

Sean O'Leary, assistant director of operations for the Aids charity the Terrence Higgins Trust, said: "Since the widespread introduction of combination therapy in the UK the health and wellbeing of people living with HIV has improved greatly.

"However, the drugs used, which include protease inhibitors, can cause serious side effects and the Terrence Higgins Trust welcomes any research which leads to the better and safer treatment of HIV."

The research is published in the Journal of the American Medical Association.