Antiretroviral hepatotoxicity in human immunodeficiency virus‐infected patients

Abstract

Background: Drug hepatotoxicity is a potentially serious adverse reaction of antiretroviral therapy in human immunodeficiency virus‐infected patients. The impact of this problem in the routine treatment of patients with human immunodeficiency virus infection is poorly defined. Objectives: Our aim was to determine what clinical features are associated with hepatotoxicity in human immunodeficiency virus‐infected patients receiving antiretroviral therapy. Methods: Consecutive patients in a primary care‐based human immunodeficiency virus clinic were evaluated for hepatotoxicity. Clinic records were used to obtain patient characteristics, as well as independent variables including CD4+ count, coexisting hepatitis C and current alcohol use. Results: Sixty‐five patients taking antiretroviral therapy were evaluated. Twenty‐four were identified to have antiretroviral hepatotoxicity. An age over 40 years (P=0.019), an absolute CD4+ count of less than 310 cells/mL (P=0.002) and coexisting hepatitis C infection (P=0.035) were significantly associated with hepatotoxicity. Patients older than 40 years had a sevenfold increased risk (risk ratio, 6.9; 95% confidence interval, 1.7–27.3) and those with an absolute CD4+ count of less than 310 cells/mL had a tenfold increased risk (risk ratio, 10.2; 95% confidence interval, 2.5–41.9) for antiretroviral hepatotoxicity, in comparison with those who were younger or who had a greater absolute CD4+ count. Of the eight patients documented to have coexisting hepatitis C infection, six (75%) were in the antiretroviral hepatotoxicity group. Conclusions: An age older than 40 years and an absolute CD4+ count of less than 310 cells/mL were significantly associated with antiretroviral‐induced hepatotoxicity. The majority of our patients with chronic hepatitis C had hepatotoxicity from antiretroviral therapy.

Review article: the use of potentially hepatotoxic drugs in patients with liver disease

“…Hepatic injury is well described for nearly all classes of antiretroviral drugs, especially nevirapine 85–87 Table 6. lists the agents in each HAART class and their associated DILI.…”

Hepatotoxicity of Antimicrobial Agents

“…Liver disease, not directly related to HIV infection, is a leading cause of death among people with HIV or AIDS. 102 Drug-induced hepatotoxicity is but one cause of hepatobiliary disorders in this population, but as antiretroviral strategies become more complex and survival improves, it has become increasingly important.…”

“…114,115 Both stavudine and zalcitabine have also been associated with hepatocellular injury with steatosis and lactic acidosis. 102 Lamivudine has been used extensively without liver injury, although hepatotoxicity was reported in two HIVpositive, pregnant women when lamivudine was used in conjunction with zidovudine and other antivirals. 116…”

The effects of antiretroviral treatment on liver function enzymes among HIV-infected out patients attending the Central Hospital of Yaounde, Cameroon

“…Till date, there has been broad variability in the criteria used in clinical studies to categorize the severity of hepatotoxicity. Some studies have utilized ALT parameters as minimal as two times the upper limits of normal [3] while others have employed an absolute threshold (e.g., >100 IU/ml), regardless of baseline liver function tests [4]. Surveys have reported an increased incidence of hepatic injury in HAART-treated patients and identified lifethreatening hepatotoxic events and end-stage liver disease in patients on antiretroviral [5].…”