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AZT Causes Anemia During Ribavirin/Interferon Therapy; EPO Improves Anemia
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Reported by Jules Levin
"Effect of AZT on Anemia and Epoetin-a use During Pegylated Interferon/Ribavirin Therapy for HCV in HIV-infected Persons"
Daniel Arvarez reported these study results at the 12th CROI (Feb 2005). Among HCV/HIV co-infected patients treated with pegylated interferon/ribavirin (PEG/RBV), we hypothesized that anemia and epoetin-a (EPO) use would be more common among patients treated with AZT. To test this hypothesis, we retrospectively evaluated hemoglobin (Hb) changes and EPO use among co-infected patients treated with PEG/RBV.
Eligible patients completed at least 12 weeks of PEG (a2a or a2b, Pegasys or PegIntron)/weight based RBV (800 to 1400 mg/day) therapy and had hemoglobin levels measured at treatment weeks 4 & 12. EPO use was prospectively recorded.
There were 217 eligible patients: male, 77%; mean age, 47 yrs; black, 35%; Pega-2b, 65%; daily RBV dose 800 mg, 12%, 1000 mg, 42%, 1200 mg, 19%; 1400 mg, 17%.
ART with AZT, 29%; ART without AZT, 52%; no ART, 19%.
Median CD4 count, 501 cells (IQR 363-738).
No significant differences were observed in pre-treatment characteristics between AZT users & non-AZT users, including mean Hb (AZT, 14.7 g/dL; no AZT, 14.6 g/dL).
At week 4, the mean Hb decrease was greater in AZT users (3.13 g/dL) compared with non-AZT users (1.96 g/dL); p<0.0001), and a Hb decrease of 5 or more g/dL was observed in 13% and 3% of AZT users & non-users, respectively (p<0.01).
In addition, RBV dose reduction was more frequent in patients on AZT compared with those not on AZT (47% >17%, p<0.0001).
EPO use was more common among patients on AZT compared with those not on AZT at treatment weeks 4 (39% > 13%, p<0.0001) and 12 (47% > 23%, p<0.0001). However, Hb levels increased following EPO use in all patients and at treatment week 12, the mean HB level was similar in AZT users (12.9 g/dL) & non-AZT users (12.9 g/dL). At week 12, AZT use was not associated with treatment discontinuation (AZT, 25%; no AZT 34%, p=0.27) or week 12 virologic failure (AZT, 41%; no AZT, 47%, p=0.44); [ed note: likely due to EPO use].
The study authors concluded that among HCV/HIV coinfected patients treated with PEG/RBV, patients on AZT had substantially greater Hb decline after 4 weeks & were more likely to use EPO than those not on AZT. While our data suggest that RBV dose reduction and EPO can effectively stabilize Hb levels without adversely affecting early vrologic response, patients on AZT must be monitored closely for treatment-related anemia and may require greater utilization of EPO than patients on other ART regimens.
Edit note from Jules Levin: there are several important considerations. (1) if possible, you may want to consider use of abacavir and/or tenofovir during PEG/RBV therapy, as these two drugs appear safer when used in combination with RBV. (2) the "d" drugs, d4T & ddI, also can have safety issues when combined with RBV; ddI is not recommended during RBV therapy as it may precipitate ddI toxicities; as well, d4T may also be associated with toxicity when used along with RBV although this is not as well established as the toxicity concerns of combining ddI & RBV. (3) reducing RBV dose, particularly during the first 12 weeks of PEG/RBV therapy can reduce viral response rates to PEG/RBV & reduce your chance to achieve a sustained viral response, clearance & eradication of HCV from the blood & liver. Studies show that dose reduction of RBV is associated with reduced viral response rates of PEG/RBV, particularly dose reduction during the first 12 weeks after starting PEG/RBV. Studies show that reducing RBV dose is more likely to reduce sustained viral response rates than reducing pegylated interferon dose. (4) EPO use can reverse the development of anemia during RBV/PEG therapy & can help to maintain RBV dose, which ought to result in an improved capacity to achieve a sustained viral response.
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