 AZT
(Retrovir) Ups Anemia Risk in HIV-HCV Coinfected Patients, But Rate Remains Low
By
Liz Highleyman
 Use
of AZT (zidovudine; Retrovir)
increases the risk of anemia in HIV-HCV
coinfected patients treated with pegylated
interferon plus ribavirin, but anemia remains uncommon and does not reduce
the likelihood of sustained response, according to the latest data from the Spanish
PRESCO study.
This prospective, multicenter trial included 389 HIV-HCV
coinfected participants: 49% with genotype 1, 39% with genotype 2 or 3, and 12%
with genotype 4. About three-quarters were on HAART and the median baseline CD4
cell count was 546 cells/mm3.
All participants were treated with 180
mcg/week pegylated interferon alpha-2a (Pegasys) plus 1000-1200 mg/day weight-based
ribavirin. Those who experienced early virological response (more than a 2
log drop in HCV RNA after 12 weeks) were randomly assigned to continue treatment
for either 48 or 72 weeks if they had genotype 1 or 4, or either 24 or 48 weeks
if they had genotype 2 or 3.
As
previously reported, overall, 36% of genotype 1 patients, 72% with genotype
2 or 3, and 33% with genotype 4 achieved sustained virological response (SVR).
Rapid virological response (RVR; undetectable HCV RNA at week 4) and adequate
doses of ribavirin were the best predictors of sustained response. Extended treatment
duration, however, did not reduce the relapse rate.
It is well established
that adequate ribavirin exposure minimizes the risk of relapse after completion
of therapy, but the drug can cause hemolytic anemia that requires dose reduction
or discontinuation. AZT can also cause anemia as a side effect.
As reported
in the December 21, 2007 advance online edition of the Journal of Hepatology,
the PRESCO team analyzed predictors of anemia among study participants, including
maximal decrease in hemoglobin throughout treatment, drops in hemoglobin to <
10 g/dL (moderate anemia) or < 8.5 g/dL (severe anemia), and premature ribavirin
discontinuation due to anemia. They also assessed the impact of anemia on SVR
rate.
Results
•
51 of the 389 participants
(13%) developed moderate anemia and 13 (3.3%) developed severe anemia.
•
In a multivariate analysis,
lower baseline hemoglobin (RR 0.14; P < 0.0001) and greater hemoglobin decreases
during the first 4 weeks of therapy (RR 4.74; P < 0.0001) were independent
predictors of moderate anemia at any point during the study.
•
Mean decreases in hemoglobin
from baseline through week 4 were significantly greater in patients receiving
AZT compared with other drugs (-3.09 vs -2.3 g/dL; P < 0.001).
•
Lower baseline hemoglobin
(RR 0.33; P = 0.04) and maximal hemoglobin decreases during treatment (RR 2.48;
P = 0.004] predicted treatment discontinuation due to anemia.
•
However, maximal hemoglobin
drops, frequency of moderate to severe anemia, and rates of ribavirin dose reduction
were comparable among patients who achieved SVR and those who did not.
Conclusion
In
conclusion, the study authors wrote, "Lower baseline hemoglobin predicts
maximal drops in hemoglobin and development of anemia in HIV-HCV coinfected patients
treated with pegylated interferon plus
ribavirin."
"The use of zidovudine is associated with greater
hemoglobin declines at week 4," they continued. "However, severe anemia
is relatively infrequent and seems not to have much impact on SVR."
Nevertheless,
they recommended, "Given the availability of alternative antiretroviral drugs,
it is advised to avoid zidovudine while receiving anti-HCV treatment."
02/01/08
Reference
M
Nunez, A Ocampo, K Aguirrebengoa, and others (PRESCO Team). Incidence of anaemia
and impact on sustained virological response in HIV/HCV-coinfected patients treated
with pegylated interferon plus ribavirin. Journal of Viral Hepatitis. December
21, 2007 [Epub ahead of print]. |
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