|
Low Incidence of Hepatotoxicity in an Italian Cohort of HIV Patients
Treated with Lopinavir/Ritonavir
In
a research letter published in the September 2, 2005 issue of AIDS,
Italian researchers of the CISAI Study Group describe hepatotoxicity
in a cohort of HIV-positive patients treated with lopinavir/ritonavir
(Kaletra).
The
investigators used a database from the SCOLTA project, an on-line
pharmaco-vigilance program involving 25 Italian infectious disease
centers. A total of 755 patients were followed, over a mean observation
period of 16 months. The incidence of severe events was low despite
the high prevalence of patients co-infected with hepatitis virus
at enrollment.
Hepatotoxicity
has always been one of the most serious adverse reactions to HAART,
often making it necessary to stop the treatment and even, fortunately
rarely, putting the patient's life at risk. This is an important
consideration in the Italian population in which the prevalence
of HIV-positive patients with chronic viral
hepatitis [hepatitis
C virus (HCV) and hepatitis
B virus] reaches 50%, and these individuals have a greater risk
of hepatic toxicity.
All
the families of antiretroviral drugs have this drawback. If one
had to list the drug groups in order of their hepatic toxicity,
the non-nucleoside
reverse transcriptase inhibitors [NNRTI] (nevirapine
and efavirenz)
are the most risky classes, followed by the protease
inhibitors and the nucleoside/tide
reverse transcriptase inhibitors.
Lopinavir/ritonavir
is at present the most widely used protease inhibitor with confirmed
efficacy. The incidence of severe hepatotoxicity in patients given
this drug ranges in different studies from 2 to 11%.
The
present study investigated the incidence of severe hepatic toxicity
in a cohort of patients treated with lopinavir/ritonavir, using
data obtained in the SCOLTA
(Surveillance Cohort Long-term Toxicity Antiretrovirals) project.
This
is an on-line reporting system for adverse reactions to antiretroviral
drugs, designed by the CISAI (Coordinamento Italiano per lo Studio
Allergia e Infezione da HIV: Italian coordination for the study
of allergy and HIV infection) group. It originated as a pharmaco-vigilance
system for newly introduced drugs, and as a sentinel scheme for
unexpected or late adverse reactions
arising during any antiretroviral treatment. It works through the
internet site www.cisai.info
and involves 25 Italian infectious disease centres. Cohorts
of patients are established for each new drug as it comes onto the
market, and these patients are followed prospectively. Data collection
and follow-up procedures for the cohorts are described elsewhere.
The
investigators only analyzed grade III and IV events, using the AIDS
Clinical Trial Group scale.
Results
· A
total of 755 patients were enrolled. A large proportion (44.4%)
had co-infection with hepatitis viruses. The mean observation period
was 16.7 months.
· The
incidence of adverse reactions was 11.0 events per 100 person-years;
the incidence was lower in previously untreated (naive) patients
than those who had already received treatment, respectively 7.0
and 11.9.
·
Metabolic
adverse events were the most common, with an incidence
of 5.4;
· Hepatic
toxicity was not frequent, at 0.59 events per 100 person-years for
the whole series, 0.54 in naive patients, and 0.48 in 'experienced'
patients.
· Only
one severe event was recorded among naive patients, compared with
four in the experienced group. Four of these five patients had HCV
co-infection.
· Two
events arose after one month of treatment and the other three after
a year, confirming the multifaceted mechanisms causing this toxicity.
In all these cases the treatment had to be stopped, and the patients
regressed.
This
study comprises the biggest series to date of patients treated with
lopinavir/ritonavir and followed prospectively outside clinical
trials. In addition, this HIV-positive population had a high prevalence
of co-infection with hepatitis viruses.
The
frequency of hepatotoxicity was actually low, unlike in other studies.
This might partly be the result of methodological differences, reflecting
how the data were collected. Retrospective studies can suffer major
selection bias. Gonzalez-Requena et al. also reported a
low incidence of adverse events, but their case series was small
and was followed up for not more than one year.
The
authors conclude, “The present study found that lopinavir/ritonavir
caused only limited hepatic toxicity in this population of HIV-positive
patients with a high prevalence of co-infection with hepatitis B
virus or HCV.”
08/22/05
Reference
P
Bonfanti and others (for the CISAI Study Group). Low incidence of
hepatotoxicity in a cohort of HIV patients treated with lopinavir/ritonavir.
AIDS 19(13): 1433-1434. September 2, 2005.
|
Link
to FDA-approved Anti-HIV Drugs
|
|
|
|
|
|
