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No Significant Association between Nevirapine (Viramune) and Liver Enzyme Elevation Regardless of Pregnancy Status

A new study of more than 2000 women published in the November 27, 2009 issue of AIDS found no significant link between use of the NNRTI nevirapine (Viramune) and liver enzyme elevation. Nevirapine use was not associated with liver toxicity in pregnant or non-pregnant women, but pregnancy itself increased the risk of liver problems in women with HIV.

Antiretroviral therapy (ART) during pregnancy significantly reduces the risk of mother-to-child transmission of HIV. Nevirapine is commonly used for this purpose in resource-limited settings, though U.S. treatment guidelines recommend that pregnant women should received a complete combination ART regimen.

Current guidelines advise that nevirapine should not be used as first-line therapy by women with a CD4 count above 250 cells/mm³ or men with more than 400cells/mm³. There is some evidence that use of with nevirapine during pregnancy is associated with an increased risk of liver toxicity, especially if a woman has a CD4 cell count above 250 cells/mm³ when she starts therapy.

Investigators therefore conducted a retrospective study to see if the association between nevirapine and liver toxicity differed according to pregnancy status. They analyzed medical records from 2050 HIV positive women: 1229 (60%) pregnant women on ART in 2 multicenter, prospective cohorts -- the Women and Infants Transmission Study and the International Maternal Pediatric Adolescent AIDS Clinical Trials protocol P1025 -- and 821 (40%) non-pregnant women from the prospective Women's Interagency HIV Study cohort.

The pregnant women were significantly younger, less likely to have viral hepatitis coinfection, and on average had higher CD4 cell counts, lower viral loads, and shorter duration of HIV infection than the non-pregnant group. However, about three-quarters of women in both groups had CD4 counts above 250 cells/mm³ (recommendations against using nevirapine for such patients were instituted in the mid-2000s).

The researchers looked at 2 outcomes: Any liver enzyme elevation (grade 1-4), and severe liver enzyme elevation (grade 3-4). Elevated liver enzymes, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST), are a sign of liver inflammation, and may occur due to drug toxicity, viral hepatitis, or a variety of other causes.

Results

• Among the pregnant women, 174 (14.2%) developed any liver enzyme elevations and 15 (1.2%) developed severe elevations.
• Among non-pregnant women, the corresponding figures were 75 (9.1%) and 5 (0.6%), respectively.
• A similar proportion of nevirapine recipients and women who never took nevirapine experienced severe liver enzyme elevations (0.8% vs 1%, respectively).
• Nevirapine was not significantly associated with risk of liver enzyme elevation, regardless of pregnancy status.
• However, pregnancy was associated overall with an increased risk of both any liver enzyme elevation and severe elevation.
• The association of pregnancy and liver enzyme elevation was observed regardless of prior history of ART or nevirapine exposure.

Based on these findings, the study authors concluded that there was no significant association between nevirapine and liver enzyme elevation, regardless of pregnancy status. They also found that pregnancy itself increased the risk of liver toxicity in women with HIV.

Finally, they wrote, "While we support close monitoring of pregnant women for clinical or laboratory evidence of hepatotoxicity with any ART regimen, our results challenge the notion that nevirapine is uniquely associated with hepatotoxicity during pregnancy."

12/1/09

Reference

DW Ouyang, DE Shapiro, M Lu, and others. Increased risk of hepatotoxicity in HIV-infected pregnant women receiving antiretroviral therapy independent of nevirapine exposure (Abstract). AIDS 23(18): 2425-2430. November 27, 2009.