Abacavir (Ziagen) in HAART Regimen May Reduce Response to Hepatitis C Treatment in Coinfected Individuals

HIV-HCV coinfected individuals tend to experience more rapid liver disease progression and respond less well to anti-HCV treatment compared with HIV negative hepatitis C patients.

Specific antiretroviral drugs in patients’ HAART regimens may influence how well they respond to hepatitis C treatment, according to a study presented at the recent 58th Annual Meeting of the American Association for the Study of Liver Diseases in Boston (November 2-6, 2007).

Current HIV-HCV coinfection treatment guidelines state that the nucleoside reverse transcriptase inhibitors (NRTIs) ddI (didanosine, Videx) and AZT (zidovudine, Retrovir) should not be used by patients taking ribavirin to treat hepatitis C, due to the risk of intensified additive side effects (mitochondrial toxicity with ddI, anemia with AZT). However, little is know about the influence on anti-HCV therapy of abacavir (Ziagen), which is a guanosine analog like ribavirin.

Investigators conducted a retrospective analysis that included all 426 HIV-HCV coinfected patients receiving first-line pegylated interferon plus ribavirin therapy between 2002 and 2005 at 3 Spanish hospitals.

Most (80%) were men, the mean age was 41 years, 80% were on HAART, and the mean CD4 count was 567 cells/mm³. At baseline, the mean HCV RNA level was 5.8 log IU/ml, 65% had HCV genotypes 1 or 4, and 40% had Metavir scores > F3.

Results

·         The overall sustained virological response (SVR) rate was 38% (26% for genotypes 1 or 4, 61% for genotypes 2 or 3).

·         Factors associated with lack of SVR in a multivariate analysis were:

o        Higher baseline HCV RNA (odds ratio [OR] 10.31; P <0.001);

o        HCV genotype 1 or 4 (OR 7.75; P <0.001);

o        Metavir score > F3 (4.03; P = 0.01);

o        Lower ribavirin plasma trough level (OR 1.64; P = 0.04).

·         The use of abacavir predicted lack of SVR when ribavirin levels were not included in the model (OR 2.04; P = 0.03)

·         The negative impact of abacavir on HCV suppression was recognized at weeks 4, 12, 48, and 72.

·         However, it was not appreciable in the subset of patients with ribavirin plasma trough levels > 2.2 mcg/ml.

Conclusion

“The use of abacavir is associated with a poorer response to pegylated interferon plus ribavirin in HIV-HCV [coinfected] patients,” the researchers concluded. “This negative impact may be overcome by high ribavirin exposure, suggesting that an inhibitory competition exists between ribavirin and abacavir.

Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain; Hepatology Unit, Hospital Valme, Sevilla, Spain; Service of Infectious Diseases, Hospital La Princesa, Madrid, Spain; Service of Internal Medicine, Hospital Puerta del Mar, Cadiz, Spain; Service of Internal Medicine, Hospital Juan Ramón Jiménez, Huelva, Spain; Service of Internal Medicine, Hospital Reina Sofía, Córdoba, Spain.

11/16/07

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