Hepatotoxicity in HIV-1-infected patients receiving nevirapine-containing antiretroviral therapy.
OBJECTIVE
To assess the incidence and risk factors for hepatotoxicity associated with nevirapine.


METHODS
A prospective cohort study in a teaching and referral hospital involving all consecutive patients who were prescribed a nevirapine-containing antiretroviral regimen between September 1997 and May 2000.


METHODS
Cutaneous and hepatic adverse reactions and clinical hepatitis were assessed. Blood analysis including plasma HIV-1 RNA CD4 cell counts, liver chemistry tests, and serology for hepatitis B and C viruses. Hepatotoxicity was defined as an increase of at least threefold in serum alanine aminotransferase or aspartate aminotransferase levels compared with baseline values.


RESULTS
Of a total of 610 patients, 82 (13.4%) were antiretroviral naive when commencing nevirapine, and 46.2 and 8.9% were coinfected with hepatitis C and B viruses, respectively. Median duration of exposure to nevirapine was 8.7 months (interquartile range 3.4--14.3). Hepatotoxicity developed in 76 (12.5%), an incidence of 13.1/100 person-years. Kaplan--Meier estimated incidence of hepatotoxicity at 3, 6 and 12 months was 3.7, 9.7 and 20.1%, respectively. In seven (1.1%) patients, hepatotoxicity was associated with clinical hepatitis, which was reversible upon discontinuation of therapy. Multivariate analysis identified the duration of prior exposure to antiretroviral drugs, hepatitis C virus, and higher baseline levels of alanine aminotransferase as independent risk factors for hepatotoxicity.


CONCLUSIONS
Hepatotoxicity but not clinical hepatitis was common in HIV-1-infected patients receiving nevirapine-containing regimens and the incidence steadily increased over time. Prolonged exposure to any antiretroviral therapy, coinfection with hepatitis C virus and abnormal baseline levels of alanine aminotransferase identified patients at a higher risk.
Martínez
E
E
Unit of Infectious Diseases, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Hospital Clínic Universitari, Barcelona, Spain.
Blanco
J L
JL
Arnaiz
J A
JA
Pérez-Cuevas
J B
JB
Mocroft
A
A
Cruceta
A
A
Marcos
M A
MA
Milinkovic
A
A
García-Viejo
M A
MA
Mallolas
J
J
Carné
X
X
Phillips
A
A
Gatell
J M
JM
D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008111:Liver Function Tests; D008297:Male; D019829:Nevirapine / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D011446:Prospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D012307:Risk Factors; D016896:Treatment Outcome; D019562:Viral Load
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine