Prospective, open-label comparative study of liver toxicity in an unselected population of HIV-infected patients treated for the first time with efavirenz or nevirapine.
OBJECTIVE
To compare the two nonnucleoside reverse transcriptase inhibitors (NNRTIs) when first introduced in an antiretroviral regimen, a prospective open-label assessment of the frequency, severity, risk factors, and outcome of hepatotoxicity was performed.


METHODS
Liver enzymes were followed-up during 18 months in patients who received efavirenz (EFV; 324 patients) or nevirapine (NVP; 299).


RESULTS
The two study groups were comparable, except for the lower baseline CD4+ count found in the EFV group. No differences were found when considering the type and duration of eventual prior anti-HIV therapy; frequency and length of protease inhibitors, methadone, or anti-tubercular drug use; HCV-HBV co-infection; other hepatobiliary disorders; and alcohol-drug abuse. The frequency of overall and first-month drug interruption proved similar in the two study groups. A hepatotoxicity characterized by at least a 2-fold increase of transaminases versus baseline was significantly linked with NVP, and the number of patients showing hepatotoxicity tended to a reduction in the EFV group. Also the time to peak transaminase alterations was shorter in the NVP group. All significant differences regarding liver-pancreatic toxicities were controlled per eventual baseline hepatobiliary-pancreatic diseases, HIV stage, and concurrent drug therapies.


CONCLUSIONS
Hepatotoxicity is a significant concern in the setting of antiretroviral-treated HIV disease. NVP-based HAART may be more hepatotoxic than EFV-based HAART, and a role is played by chronic liver disorders. Although concurrent hepatobiliary disorders and the possible hepatotoxicity of antiretrovirals do not represent contraindications to nonnucleoside inhibitor use, strict monitoring is recommended.
Manfredi
Roberto
R
Department of Clinical and Experimental Medicine, Division of Infectious Diseases, University of Bologna Alma Mater Studiorum, S. Orsola Hospital, Bologna, Italy. manfredi@med.unibo.it
Calza
Leonardo
L
Chiodo
Francesco
F
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000480:Alkynes; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D001219:Aspartate Aminotransferases / Q000097:blood; D048588:Benzoxazines; D018791:CD4 Lymphocyte Count; D056486:Chemical and Drug Induced Liver Injury; D002802:Cholinesterases / Q000097:blood; D015331:Cohort Studies; D003521:Cyclopropanes; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development*; D006801:Humans; D008107:Liver Diseases / Q000097:blood / Q000201:enzymology; D008297:Male; D019829:Nevirapine / Q000009:adverse effects* / Q000627:therapeutic use; D010078:Oxazines / Q000009:adverse effects* / Q000627:therapeutic use; D011446:Prospective Studies; D012367:RNA, Viral / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D012709:Serum Albumin / Q000378:metabolism; D005723:gamma-Glutamyltransferase / Q000097:blood
D000480:Alkynes; D048588:Benzoxazines; D003521:Cyclopropanes; D010078:Oxazines; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors; D012709:Serum Albumin; D019829:Nevirapine; D005723:gamma-Glutamyltransferase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D002802:Cholinesterases; D000469:Alkaline Phosphatase; C098320:efavirenz