Liver
Toxicity Related to Raltegravir (Isentress) Is Uncommon among HIV Patients, including
those with HIV-HCV Coinfection
 | HIV
patients receiving the integrase inhibitor raltegravir (Isentress) seldom experience
drug-related liver toxicity, even if they are coinfected with hepatitis C virus
(HCV), according to a poster presentation at the 5th International AIDS Society
Conference on HIV Pathogenesis, Treatment, and Prevention (IAS 2009) last month
in Cape Town, South Africa. |
By
Liz Highleyman Raltegravir
has generally demonstrated good safety and tolerability in clinical trials, which
typically have recruited HIV patients without serious underlying conditions such
as liver disease. Therefore, HIV positive patients
with chronic viral hepatitis B or C
represent a large group for whom the tolerability of raltegravir still remains
to be assessed. Researchers
at Hospital Carlos III in Madrid, Spain, which treats many HIV-HCV
coinfected individuals, evaluated liver toxicity among antiretroviral
treatment-experienced patients who started raltegravir between December 2005
and January 2009. Out
of a total 311 patients who started the drug during this period, the present analysis
included 126 HIV monoinfected and 92 HIV-HCV coinfected participants. Most (80%)
were men, the mean age was 46 years, the median CD4 cell count was 400 cells/mm3,
and 64% had plasma HIV RNA < 50 copies/mL. At
baseline, month 1, and every 3 months thereafter, the investigators analyzed clinical
data, laboratory parameters, and liver stiffness (a method of estimating extent
of liver damage using the transient elastometry, or FibroScan, method). Liver
toxicity was classified according to baseline alanine aminotransferase (ALT) values.
Any toxicity was defined as > 1.25-fold above the upper limit of normal (31
IU/L) in patients with normal ALT at baseline, or 1.25 times the baseline level
in those who started with elevated ALT. Grade 3 (serious) hepatotoxicity was defined
as ALT increases > 3.5-fold the normal or baseline level, while grade 4 (severe
or life-threatening) liver toxicity was defined as > 5-fold the normal or baseline
level. Results  | 10
(7.9%) HIV monoinfected patients developed any degree of liver toxicity after
starting raltegravir, compared with 23 (25%) HIV-HCV coinfected patients (P <
0.001). | | Only
3 patients -- all of them coinfected -- experienced grade 3 or 4 hepatotoxicity.
| | This
occurred at 1 month in 1 patient and at 15 months in the other 2 patients with
serious hepatotoxicity. | | In
all 3 of these patients, other factors related to liver damage were also involved.
| | A
multivariate analysis revealed that HIV-HCV coinfection was the only independent
variable associated with any degree of liver toxicity (P = 0.03). | | The
main reasons for raltegravir discontinuation were poor adherence (n=5), virological
failure (n=3), and headache (n=1). |
"Elevations
in liver enzymes are rarely seen in HIV patients treated with raltegravir-containing
regimens," the investigators stated. "They are uniformly mild and no
cases of grade 3-4 hepatotoxicity could be attributed to raltegravir in our patients,
40% of whom were coinfected." Based
on these findings, they concluded, "The good hepatic safety profile of raltegravir
should be added to its overall good tolerability. Raltegravir may be an interesting
option in HIV-HCV coinfected patients." Hospital
Carlos III, Infectious Diseases Department, Madrid, Spain. 8/4/09 Reference
A
Mena, F Blanco, M Córdoba, and others. Hepatic safety profile of raltegravir
in HIV patients with chronic hepatitis C. 5th International AIDS Society Conference
on HIV Pathogenesis, Treatment, and Prevention (IAS 2009). July 19-22, 2009. Cape
Town, South Africa. Abstract
WePeB230.
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