Safety
of Atazanavir in Patients with HIV/HCV or HIV/HBV Coinfection HIV
positive patients with pre-existing liver disease - including those coinfected
with hepatitis B or hepatitis
C virus (HBV or HCV, respectively) - are more likely to develop liver toxicity
while taking antiretroviral medications, compared with HIV
monoinfected individuals. The
second-generation protease inhibitor (PI) atazanavir
(Reyataz) is less likely to cause liver enzyme elevations than some other
drugs in its class, but more likely to cause elevated bilirubin levels, which
may cause jaundice (yellowing of the skin and whites of the eyes). A
study presented at the recent XVI International AIDS Conference in Toronto examined
the safety of atazanavir,
with or without ritonavir (Norvir),
in coinfected individuals. Researchers
from Bristol-Myers Squibb conducted an analysis that included 866 total participants
in 4 clinical trials of atazanavir: 
BMS089 (atazanavir vs atazanavir/ritonavir):
treatment-naive subjects, 162 HIV monoinfected and 37 HIV/HBV or HIV/HCV coinfected;
BMS034 (atazanavir vs efavirenz
[Sustiva]): treatment-naive subjects, 354 HIV monoinfected and 50 coinfected;
BMS043 (atazanavir vs lopinavir/ritonavir
[Kaletra]): treatment-experienced subjects, 116 HIV monoinfected and 28 coinfected;
BMS089 (atazanavir/ritonavir
vs lopinavir/ritonavir): treatment-experienced
subjects, 100 HIV monoinfected and 19 coinfected.
Results
652 total patients received unboosted atazanavir and 214 received atazanavir/ritonavir
for 48-59 weeks, representing 1100 patient-years of atazanavir exposure.
134 total patients (15%) were coinfected with HBV or HCV.
Percentages of subjects with Grade 3 or 4 (G3/4) elevations in alanine aminotransferase
(ALT) and aspartate aminotransferase (AST) are shown in the following table:
|
Study |
089 |
034 |
043 |
045 |
|
Co-Infection |
Pos |
Neg |
Pos |
Neg |
Pos |
Neg |
Pos |
Neg |
|
N |
37 |
162 |
50 |
354 |
28 |
116 |
19 |
100 |
|
ALT, G3/4,% |
atazanavir |
15 |
0 |
12 |
3 |
15 |
6 |
- |
- |
|
ALT, G3/4,% |
Atazanavir/
ritonavir |
29 |
<1 |
- |
- |
- |
- |
26 |
1 |
|
AST, G3/4,% |
atazanavir |
10 |
<1 |
10 |
<1 |
7 |
3 |
- |
- |
|
AST, G3/4,% |
Atazanavir/
ritonavir |
12 |
<1 |
- |
- |
- |
- |
11 |
2 |
Among both treatment-naive and treatment-experienced subjects, rates of Grade
3-4 ALT/AST elevation were higher for patients with HBV or HCV coinfection compared
with HIV monoinfected patients.
Grade 3-4 total bilirubin elevation rates were comparable in coinfected and HIV
monoinfected patients.
Coinfected and monoinfected subjects had similar rates of Grade 2-4 treatment-related
adverse events including jaundice and scleral icterus (yellowing of the whites
of the eyes).
Rates of treatment discontinuation due to adverse events were similar in the coinfected
and monoinfected groups.
Overall rates of adverse events and treatment discontinuations in the coinfected
patients were low.
Conclusion In
conclusion, the researchers wrote, "Similar to other [antiretrovirals], subjects
with HBV and/or HCV coinfection had a higher rate of G3/4 ALT/AST elevations."
In contrast, "G3/4 bilirubin elevations, overall [adverse events], and liver-related
[adverse events] had a comparable frequency in subjects with and without coinfection,
suggesting that atazanavir and atazanavir/ritonavir are safe treatment alternatives
in this population." 9/12/06 Reference
J
Witek, S Mc Callister, L Odeshoo, and others. Safety of atazanavir (ATV) and atazanavir/ritonavir
(ATV/r) in subjects co-infected with HIV and hepatitis B and/or C: 1100 subject-years
of treatment exposure. XVI International AIDS Conference, Toronto. August 13-18,
2006. Abstract WEPE0054/10066.
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