icon- folder.gif   Conference Reports for NATAP  
  16th CROI
Conference on Retroviruses and Opportunistic Infections Montreal, Canada
February 8-11, 2009
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Abacavir Use is Not Associated with Lack of Virologic Response in ARV-treated HIV/HCV-Coinfected Patients Receiving PEG-IFN and Ribavirin
  Reported by Jules Levin
CROI 2009 Feb 8-12 Montreal
Valerianna Amorosa, MD1,2, Jihad Slim, MD3; Karam Mounzer, MD4; Christopher Bruno, MD5, Margaret Hoffman-Terry, MD6; Zachariah Dorey-Stein, BA1; Thomas Ferrara, BS2; Laura Redmond, PharmD2; Jay Kostman, MD1; Vincent Lo Re III, MD, MSCE1,21. University of Pennsylvania, 2. Philadelphia VAMC, 3. St. Michael's Hospital, Newark, 4. Jonathan Lax Treatment Center, 5. Drexel University, 6. Lehigh Valley Hospital, Allentownx Treatment Center, 5. Drexel University, 6. Lehigh Valley Hospital, Allentown
This study, COL112238, was supported in part by funding from GlaxoSmithKline


Background: The effect of abacavir (ABC) on virologic response to combination PEG-interferon (IFN) plus ribavirin (RBV) remains unclear. Previous studies, conducted mainly in clinical trials settings, have reported conflicting results, and did not restrict analyses to subjects receiving ARV therapy. We examined whether ABC increased the risk of HCV virologic non-response during PEG-IFN + RBV therapy among ARV-treated HIV/HCV patients in coinfection clinics.
Methods: We conducted a retrospective cohort study among ARV-treated HIV/HCV patients initiating PEG-IFN alfa-2a or -2b plus RBV between Jan. 2001 and June 2007 at 6 U.S. coinfection treatment centers. ABC represented the exposure. Study outcomes included: 1) early virologic failure, defined as a <2 log IU/mL decrease in the HCV RNA at 12 weeks of therapy, and 2) sustained virologic response (SVR), defined as an undetectable HCV viral load 24 weeks after treatment discontinuation. Logistic regression models determined associations between ABC and early virologic failure and SVR. Sub-analyses were performed by genotype (GT) and among subjects with optimal weight-based doses.
Results: Among 212 subjects receiving ARVs, 74 (35%) received ABC. Overall, the median decline in HCV viral load (VL) at 12 weeks was smaller but not significantly different between ABC users and non-users (1.15 vs. 1.94 IU/mL; p=0.5). Among 137 subjects who were prescribed and maintained on weight- based PEG-IFN and RBV doses, median HCV VL declines at 12 weeks were similar for ABC users versus non-users (2.20 vs. 2.23 log IU/mL; p=0.8). Among subjects with GT 1/4, median HCV VL declines at 12 weeks were smaller for subjects prescribed ABC (1.15 vs. 1.56 log IU/mL), but this was not statistically significant (p=0.6). Early virologic failure rates in these subjects were similar between those receiving ABC versus non-users (41 [55%] vs. 69 [50%]; Adjusted OR, 0.87; 95% CI, 0.0.45-1.70). ABC use was not associated with a higher risk of early virologic failure in GT 1/4 subjects even after controlling for age, sex, race, stage of fibrosis, and baseline HCV viral load (adjusted OR, 1.0; 95% CI, 0.50-2.0). ABC use also did not decrease the risk of SVR in GT 1/4 subjects (adjusted OR 0.72; 95% CI, 0.2-2.07).
Conclusions: Among ARV-treated HIV/HCV-coinfected subjects, abacavir use was not associated with a decrease in early virologic response or SVR rates, particularly in those patients who received appropriate doses of PEG-IFN + RBV.
The response rate to HCV therapy with pegylated-interferon and ribavirin in HIV infected persons participating in clinical trials has been below the response rates noted in HCV mono-infected trials.1
Antiretrovirals themselves could play contributing roles due to additive toxicities and potential drug interactions between HIV and HCV antivirals.
The question of decreased response rates to HCV therapy on HIV-infected subjects on abacavir arose initially from a post-hoc analysis of the RIBAVIC study which demonstrated a correlation between abacaviruse and early virologic failure in a mixed genotype population.2
The theoretical reason for a decreased response on abacaviris intracellular competition.
Given already limited antiretroviral options in coinfected subjects undergoing HCV therapy, determining if and to what extent abacaviris associated with a decrease in HCV treatment response becomes more vital.
We studied this question in a retrospective North American cohort and limited the comparison to all those patients on HAART while undergoing HCV therapy.