Given
that drug-related hepatotoxicity (liver toxicity) is an important complication
of antiretroviral therapy, researchers
conducted a retrospective cohort study to assess the incidence of and risk factors
for hepatotoxicity among HIV-infected individuals
taking HAART in South Africa.
The study, described in the June 2007 issue
of AIDS, included participants in a workplace HIV care program that uses
a first-line regimen consisting of efavirenz
(Sustiva) plus AZT (Retrovir)
plus 3TC (Epivir), and provides
routine clinical and laboratory monitoring. Almost all (95%) received efavirenz-based
regimens, but 5% instead took nevirapine
(Viramune).
The analysis included 868 patients who started their first
HAART regimen between November 2002 and December 2005, and who had baseline and
follow-up alanine transaminase (ALT) and aspartate aminotransferase (AST) liver
enzyme tests. Most (94%) were male, the median age was 41 years, the median nadir
(lowest-ever) CD4 cell count was 136 cells/mm3, and the median viral load was
4.7 log copies/mL. Among those with available test results, 20.7% were positive
for hepatitis B surface antigen (HBsAg). More than
half had a history of tuberculosis (TB),
and 25% received treatment for active TB while on HAART.
The researchers
identified severe liver toxicity occurring during the first 12 months on HAART.
Severe hepatotoxicity was defined as ALT or AST levels greater than 5 times the
upper limit of normal for patients starting with normal values, or 3.6 times the
baseline value if already elevated.
Potential
risk factors -- including concomitant medication use, tuberculosis, and hepatitis
B and C coinfection -- were determined from clinical records, database queries,
and serological testing. Associations with hepatotoxicity were investigated using
Cox proportional hazards modeling.
Results
• Among the 868 subjects followed
for a median 239 days, 97 subjects (11%) experienced at least moderate hepatotoxicity
(19.7 episodes per 100 person-years [PY]).
•
These included 40 subjects (4.6%) with severe hepatotoxicity (7.7 episodes
per 100 PY).
• Even
among patients with severe episodes, however, the clinical impact was "modest"
in most cases.
• 8
subjects (20%) changed therapy due to liver toxicity.
•
Among patients with severe episodes, there was 1 death due to liver
failure.
• Concurrent
use of drugs for TB treatment or prophylaxis increased the risk of severe liver
toxicity by 8.5-fold.
• Being
HBsAg positive increased the risk by 3.0-fold.
•
Having a nadir CD4 count below 100 cells/mm3 increased the risk by
1.9 fold.
• Baseline liver enzyme elevation
did not predict severe hepatotoxicity while on HAART.
•
The proportion of patients with severe hepatotoxicity while on HAART
(4.6%) was similar to the proportion with liver enzyme elevations > 5 times
the upper limit of normal before starting antiretroviral
therapy (4.0%).
Conclusion
In
conclusion, the authors wrote, "In this African antiretroviral therapy cohort,
we found a low incidence of and minimal morbidity due to hepatotoxicity. HBsAg
and concomitant tuberculosis therapy significantly increased the risk of hepatotoxicity."
Aurum
Institute for Health Research, Johannesburg, South Africa; Johns Hopkins University
School of Medicine, Baltimore, MD; Toga Laboratories, Johannesburg, South Africa;
University of Pretoria, South Africa; London School of Hygiene and Tropical Medicine,
London, UK.
07/06/07
Reference CJ
Hoffmann, S Charalambous, CL Thio, and others. Hepatotoxicity in an African antiretroviral
therapy cohort: the effect of tuberculosis and hepatitis B. AIDS 21(10):
1301-1308. June 2007.
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Given
that drug-related hepatotoxicity (liver toxicity) is an important complication
of 
