The use of nevirapine in post-exposure prophylaxis (PEP) can potentially cause an abnormal liver function according to Italian investigators writing in the September 5th edition of AIDS. Less severe liver-related problems were also seen in people taking other PEP regimens, but in all cases resolved once the course of antiretroviral therapy was completed or stopped.
PEP is widely used after occupational exposure to HIV, and its use after potential sexual exposure to HIV is increasing. However, some clinicians are reluctant to offer PEP for non-occupational exposures, often citing a fear of side-effects. Liver problems have previously been observed with nevirapine-containing PEP regimens, and the use of the drug for PEP is now rare. Other side-effects have occured after PEP has been prescribed. Earlier this year, body fat changes were reported in a man who received two courses of PEP (see link below). In order to evaluate the effect of PEP on liver function, Italian investigators conducted a retrospective review of the medical records of 655 individuals who received PEP in Italy between 1996 and 2002.
Individuals were divided into three groups, according to the type of PEP regimen they received. Group A consisted of patients who received two NRTIs (n=207). Group B was made up of individuals who were prescribed two NRTIs and a protease inhibitor (n=429). People who received a regimen including an NNRTI were included in Group C (n=19).
To be included individuals had to have received at least five days of PEP, and have had their ALT and AST levels measured at baseline and within five days of discontinuing PEP. Changes in liver function between baseline and the second test were categorised according to a toxicity grading used by the AIDS Clinical Trials Group.
PEP was prescribed for an average of 30 days, although there were variations between the three groups of patients, with individuals treated with an NNRTI receiving an average of 25 days treatment.
Significant variations were noted between the three groups of patients in the frequency with which liver related problems occurred and in their severity. In Group A, ALTs or ASTs became mildly elevated in six cases within ten to 15 days of starting therapy, but all the individuals were able to complete their course of PEP without experiencing any further worsening of their liver function.
A total of 15 people provided with a PEP regimen including a protease inhibitor experienced an elevation in their ALT and AST levels. Two patients treated with a regimen containing AZT, 3TC plus indinavir or nelfinavir experienced a severe/moderate increase in ALT/AST levels. Moderate increases occurred in four individuals, and mild liver toxicities were observed in eight patients. A total of four patients (two with mild and two with moderate to severe increases in ALT/ASTs discontinued PEP).
Of the 19 patients treated with NNRTIs, seven received efavirenz. None of these individuals experienced alterations in their liver function. Of the twelve patients treated with nevirapine, two developed severe increases in ALT/AST levels within four weeks of starting treatment. One required hospitalisation, but both recovered promptly once PEP was stopped. A moderate elevation of ALT/AST levels occurred in one patient, involving rash and PEP was stopped at day 24. One other patients experienced a mild increase in liver function.
In all patients in all treatment groups, ALT/AST levels returned to normal once PEP was stopped.
Sixteen patients in the study were infected with hepatitis B virus or hepatitis C virus, but none of these individuals experienced any liver related side-effects.
The investigators conclude that alterations in ALT/AST levels are rare in people treated with a PEP regimen containing NRTIs with or without a protease inhibitor. However, “our study confirms previous data showing that hepatotoxicity can be more frequent and severe in nevirapine-containing regimens. Because of the high incidence of severe toxicity, nevirapine use in PEP should be restricted to highly selected cases, in which resistance...indicates nevirapine as the sole possible alternative, with a close control of the liver function.”
Further information on this website
Treatment during primary infection - PEP - overview
Nevirapine use in PEP: concerns over rash - news story
Lipodystrophy develops on HIV-negative man after receiving PEP - news story
PEP for non-occupational exposure to HIV discussed in JAMA - news story
Nevirapine - overview
Drenaggi D et al. Drug induced aminotransferase alterations during antiretroviral HIV post-exposure prophylaxis. AIDS 17: 1988 - 1990, 2003.