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Efavirenz Levels Normal in People Coinfected with HBV or HCV
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8th International Workshop on Pharmacology of HIV Therapy
April 16-18, 2007, Budapest
Mark Mascolini
Efavirenz concentrations in people coinfected with hepatitis B or C (HBV or HCV) generally matched levels of people infected only with HIV through 24 months of follow-up in a Lisbon study [1]. Earlier research by a different group found higher rates of toxic efavirenz levels in HCV-coinfected people with cirrhosis than in those without cirrhosis [2], but that study did not evaluate whether HCV pushes efavirenz levels higher or whether high efavirenz levels further liver damage in people with less advanced liver disease.
Higher efavirenz concentrations might be expected in people with hepatitis-related liver damage because the nonnucleoside depends on the liver for its metabolism and excretion. A sick liver might metabolize efavirenz inefficiently and so allow levels of the drug to build up, possibly to toxic volumes. The cirrhosis study did not find toxic protease inhibitor (PI) levels in people with cirrhotic livers, even though PIs also use the liver for their metabolism [2].
Sofia Pereira (New University of Lisbon) and colleagues at a Lisbon hospital studied 27 people taking efavirenz for more than 1 month, including 18 without coinfection and with normal liver function and 9 HBV- or HCV-coinfected people with mild liver impairment (Child-Pugh class A). The researchers measured efavirenz levels 8 to 14 hours after dosing at least every 6 months through 24 months of follow-up.
The study groups did not differ much in age, gender, or body mass index. Majorities in both groups used AZT and 3TC with efavirenz. Time taking efavirenz was slightly but not significantly longer in the people with hepatitis and liver impairment (20 months) than in those with a healthy liver (14 months). Pereira also measured three markers of liver function in all study participants: hepatocyte (liver cell) integrity, cholestasis (slowed or stopped bile flow), and liver mass. The two groups did not differ in any of these measures.
Efavirenz levels proved significantly lower at the start of follow-up in coinfected people (1.56 +/- 0.93 mg/L) than in people infected only with HIV (1.86 +/- 0.16 mg/L) (P = 0.036). But concentrations of the nonnucleoside did not differ significantly between the two groups at months 6, 12, 18, or 24.
Alanine aminotransferase (ALT) readings were significantly lower in the coinfected group at month 24, averaging 34 +/- 3 IU/L versus 58 +/- 9 IU/L in people infected only with HIV (P = 0.0297). But Pereira doubts that difference has any clinical meaning because the aspartate aminotransferase (AST)/ALT ratio was near normal in both groups.
The Lisbon team concluded that HBV or HCV in itself does not predispose people to higher--possibly toxic--efavirenz concentrations. Pereira suggested that people coinfected with HBV or HCV do not have to adjust their efavirenz dose because of coinfection alone. And she saw no need for extra-vigilant therapeutic drug monitoring in coinfected people taking efavirenz.
References
1. Pereira S, Caixas U, Branco T, et al. Does HCV or HBV infection influence efavirenz plasma concentrations in HIV-infected patients with well-compensated disease? 8th International Workshop on Pharmacology of HIV Therapy. April 16-18, 2007. Budapest. Abstract 4.
2. Barreiro P, Rodriguez-Novoa S, Labarga P, et al. Influence of liver fibrosis stage on plasma levels of antiretroviral drugs in HIV-infected patients with chronic hepatitis C. J Infect Dis. 2007;195:973-979.
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