Study details

Doctors in Spain analysed data from 610 subjects who were using nevirapine (Viramune)-containing regimens. The subject profile at the start of the study was as follows:

• 30% female, 70% male
• 60% had AIDS
• 80% were using three anti-HIV drugs
• 20% were using four or more anti-HIV drugs
• 31% used a protease inhibitor in addition to nevirapine
• 13% had never used anti-HIV drugs
• 46% had hepatitis C virus (HCV) infection
• 9% had hepatitis B virus (HBV) infection
• average CD4+ count – 279 cells
• average viral load – about 10,000 copies

Other than the non-nuke nevirapine, drugs commonly used by subjects included the following:

• d4T (Zerit)
• 3TC (lamivudine, Epivir)
• AZT
• ddI (Videx)
• nelfinavir (Viracept)

The purpose of the study was to find out about nevirapine's impact on the liver. To do this, technicians regularly tested blood samples from study subjects checking for liver enzyme levels. This is because when the liver is damaged, levels of liver enzymes in the blood rise above their normal range. The following enzyme levels were measured:

• ALT – alanine aminotransferase
• AST – aspartate aminotransferase
• AP – alkaline phosphatase
• GGT – gammaglutamyl transferase

The researchers defined liver toxicity during the study as any increase in the liver enzymes AST or ALT that was three times greater than their level at the start of the study.

Results — toxicity

76 subjects (about 12%) developed liver toxicity (as defined previously). The following proportion of subjects had higher-than-normal levels of the following enzymes:

• 29% – GGT
• 11% – ALT
• 7% – AST
• 1% – AP

Deaths

Twelve subjects died from causes other than nevirapine-related toxicity. The causes of death were as follows:

• cancer – 5 subjects
• CMV (cytomegalovirus) – 1 subject
• TB (tuberculosis) – 1 subject
• bacterial pneumonia – 2 subjects
• swollen pancreas gland (pancreatitis) – 2 subjects
• liver damage – 1 subject

Stopping nevirapine

239 subjects (nearly 40%) stopped taking nevirapine during the study, most commonly because of rising viral load.

Hepatitis

Only 7 subjects (1%) had to stop taking nevirapine because they developed the following signs/symptoms of hepatitis:

• weakness
• fatigue
• nausea/vomiting
• fever
• jaundice

The researchers noted that six of the seven subjects were also co-infected with HCV; two were also chronic "alcohol abusers" and one had HBV. On average, hepatitis developed about two months after subjects began using nevirapine.

Who is at risk for liver damage?

Researchers came to the following conclusions about which factors place people at increased risk for liver damage associated with nevirapine use:

• for every year of prior use of anti-HIV medication before subjects used nevirapine the risk of liver damage increased by 10%
• subjects who were co-infected with HCV were twice as likely to develop liver toxicity as subjects who did not have this infection
• subjects with higher-than-normal levels of the liver enzyme ALT were 1½ times more likely to develop liver damage than subjects who had normal levels of ALT

The researchers noted that the risk of nevirapine-associated liver damage increased "steadily over time."

REFERENCE

Martínez E, Blanco JL, Arnaiz JA, et al. Hepatotoxicity in HIV-1-infected patients receiving nevirapine-containing antiretroviral therapy. AIDS 2001;15(10):1261-1268.

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Copyright © 2001 - 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.

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