Summary

There have been isolated reports that some HIV-positive people who are also co-infected with hepatitis B or C virus may be at increased risk of liver damage from HAART. The drugs that make up combinations used in HAART are processed by the liver, and the use of these drugs may pose an additional burden for livers already damaged by hepatitis. Researchers at Johns Hopkins University monitored nearly 300 HIV-positive subjects who were co-infected with hepatitis B or C virus. Researchers prescribed various anti-HIV regimens and monitored the subjects over a period of two years to observe the impact of HAART on the liver. According to their results, the researchers found that most subjects with long-term hepatitis virus infection were able to tolerate HAART. Ritonavir was the only drug associated with severe liver damage.

Study details

Researchers reported details on 298 HIV-positive subjects (75 females and 233 males), about 54 per cent of whom were injection drug users. Subjects were divided into two groups, based on which treatment they received:

• HAART
• Nukes only (AZT, ddC, ddI, d4T, 3TC)

Among people who received HAART, key lab values were as follows:

• Median CD4+ count - 109 cells
• Median viral load - 55,000 copies

Among people who received nukes alone, key lab values were as follows:

• Median CD4+ count - 215 cells
• Median viral load - 23,000 copies

While there are many liver enzymes, researchers choose to monitor only two:

• ALT (alanine aminotransferase)
• AST (aspartate aminotransferase)

When the liver is damaged, high levels of liver enzymes appear in the blood. Researchers therefore detected liver damage by regularly checking for high liver enzymes in subjects' blood.

Results - liver toxicity

Severe liver damage occurred in 31 subjects or 10 per cent of the study's 298 subjects. It took as little as two months and as long as five months before severe liver toxicity appeared. The median time was four months.

Four subjects died within 90 days of being diagnosed with severe liver damage. The doctors noted, however, that none of these deaths were due to liver-related problems.

Results - liver damage and hepatitis

Researchers found that 88 per cent of subjects who were infected with HIV and either hepatitis B or C viruses did not experience severe liver damage during the study.

Results - liver damage and protease inhibitors

The researchers found that nearly half the cases of severe liver toxicity occurred in people who were taking ritonavir. Moreover, according to the researchers calculations, people who took ritonavir were five times more likely to experience severe liver damage than those who were not taking this drug. Other protease inhibitors - indinavir, nelfinavir and saquinavir - were not associated with the development of severe liver damage.

The doctors state that their results suggest that anti-HIV therapy should not be "withheld" from HIV-positive people who also have chronic viral hepatitis.

REFERENCE

1. Sulkowski MS, Thomas DL, Chaisson RE, Moore RD. Hepatotoxicity associated with antiretroviral therapy in adults infected with human immunodeficiency virus and the role of hepatitis C or B virus infection. Journal of the American Medical Association 2000;283(1):74-80.

20000201
CATE10506

Copyright © 2000 - TreatmentUpdate. Reproduced with permission. Reproduction of this article (other than one copy for personal reference) must be cleared through the Editor, The Canadian AIDS Treatment Information Exchange, 555 Richmond St. West, Suite 505, Box 1104, Toronto, ON, M5V 3B1 • Phone: 416-203-7122 • Toll Free: 1-800-263-1638 • Fax: 416-203-8284  http://www.catie.ca