Hepatitis B and C virus co-infection and the risk for hepatotoxicity of highly active antiretroviral therapy in HIV-1 infection.
OBJECTIVE
To investigate the risk of hepatotoxicity after initiation of protease inhibitor-containing highly active antiretroviral therapy (HAART) for HIV-1 infected patients with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) co-infection.


METHODS
Retrospective study with 394 HIV-1-infected patients initiating HAART at a single university clinic.


METHODS
Liver enzyme elevation (LEE) was defined as alanine aminotransferase or aspartate aminotransferase at least five times the upper limit of normal and an absolute increase of > 100 U/l. Relative risks for time to LEE were estimated using Cox proportional hazards models.


RESULTS
Of 394 patients 7% were hepatitis B surface antigen (HBsAg)-positive and 14% were anti-HCV-positive. Patients with chronic hepatitis had a higher risk for LEE compared with patients without co-infection: 37% versus 12% respectively. After adjustment for higher baseline transaminases, the presence of HBsAg or anti-HCV remained associated with an increased risk of LEE - relative risk 2.78 (95% confidence interval, 1.50-5.16) and 2.46 (95% confidence interval, 1.43-4.24) respectively. In patients with LEE, transaminases declined whether HAART was continued or modified. Of patients with chronic HBV infection 38% lost HBeAg or developed anti-HBe after initiation of HAART, and one seroconverted from HBsAg-positive to anti-HBs-positive. However, there was no clear relationship with LEE.


CONCLUSIONS
HIV-1-infected patients co-infected with HBV or HCV were at considerably higher risk of developing LEE when HAART was initiated compared with patients without co-infection, but it is usually not necessary to modify antiretroviral therapy.
den Brinker
M
M
National AIDS Therapy Evaluation Center (NATEC), Department of Internal Medicine, Academic Medical Center, University of Amsterdam, The Netherlands.
Wit
F W
FW
Wertheim-van Dillen
P M
PM
Jurriaans
S
S
Weel
J
J
van Leeuwen
R
R
Pakker
N G
NG
Reiss
P
P
Danner
S A
SA
Weverling
G J
GJ
Lange
J M
JM
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D019380:Anti-HIV Agents / Q000009:adverse effects*; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000175:diagnosis / Q000209:etiology*; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D015497:HIV-1; D019694:Hepatitis B, Chronic / Q000150:complications; D006526:Hepatitis C / Q000150:complications; D006801:Humans; D008111:Liver Function Tests; D008297:Male; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects*
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase