• Relationships Between Nevirapine Plasma Levels, Chronic Hepatitis C, and the Development of Liver Toxicity (Abstract H-1731)
  Authored by M. Nunez, V. Soriano, D. Gonzalez-Requena, J. Gonzalez-Lahoz
  Poster Presentation: View the original abstract

If themes tend to emerge at conferences, then hepatitis C and HIV was one of the themes at this year's ICAAC. Up to 35 percent of people living with HIV and AIDS may also be infected with hepatitis C. As people with HIV are living longer and longer, liver disease from hepatitis C is becoming a bigger concern. Over the last several years, many HIV/AIDS clinics have reported that liver disease was among the leading causes of death; in fact, it was a cause more often than HIV itself. HIV accelerates the course of hepatitis C disease, though not all patients with hepatitis C will progress or get sick.

In general, though, there were few striking new reports at this conference. This paper looked at the correlation of nevirapine (NVP, Viramune) drug levels and liver toxicity in patients with hepatitis C. The reasons for doing this were two fold. First, it is possible that patients with liver disease will have difficulty metabolizing drugs that pass through the liver (as do most HIV medicines) and will have higher drug levels or more toxicity. Second, it is possible that drug levels are associated with toxicity.

There appear to be two main types of liver toxicity associated with nevirapine. The first is elevation of liver enzymes without any symptoms or serious problems. This is reasonably common, and can occur at any time. However, all HIV medications can do this, and several studies show that this type of toxicity is no more common with nevirapine than with any other HIV drug. People with abnormal liver enzyme levels at baseline and people with hepatitis B or C are more likely to have this type of toxicity.

The second is quite rare, but of greater concern. This is liver inflammation with symptoms, usually a rash, that occur within the first six weeks of starting. The risk factors for this appear to be gendered -- i.e., females are more likely to have this symptom, having a high CD4 count, or perhaps taking nevirapine without being HIV infected. This appears to be more of a hypersensitivity reaction and is cause (click here for a report from Barcelona).

This small study looked simply at the first type -- that is, enzyme elevations -- in 70 people who began nevirapine-based triple combination therapy. They looked at people who had hepatitis C, who developed enzyme elevations, and at patients' drug levels. Thirty-two of 70 people in the study were hepatitis C infected. Thirty-three out of the 70 developed at least one abnormal enzyme level at one point. Those with hepatitis C were 11 times more likely to have abnormal enzymes. Those with enzyme elevations, on average, had slightly higher nevirapine blood levels than those who did not. However, there was no difference in the blood levels between those with Hepatitis C and those without. No serious liver problems developed in any patient.

The take-home point was that hepatitis C does not interfere with the metabolism of nevirapine or lead to higher drug levels. This is reassuring, but may not be true for people with very severe end stage liver disease. Those with hepatitis C were again shown to have more abnormal liver enzymes when starting nevirapine-based HAART. This is not new, and is true for all types of HAART. It does, however, emphasize the need to monitor blood tests while patients are on therapy in order to watch for toxicity. Generally, blood chemistries should be checked two to four weeks after starting a new regimen and at least every three months.