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Early Changes in HCV Viral Load During the First 24 Hours of Treatment Exhibit a Very High Negative Predictive Value of Sustained Virological Response
in HCV/HIV Coinfected Patients
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Reported by Jules Levin
ICCAC Sept 11 2009 San Francisco
Natalia Laufer1,2, Federico Bolcic1, Eugenia Socias2, Mercedes Cabrini2, Marķa Jose Rolon2, Rita Reynoso1, Nilda Schvachsa1,
Hector Perez2, Horacio Salomon1, Pedro Cahn2, Jorge Quarleri1.
1Argentinean National Reference Center for AIDS, University of Buenos Aires, 2Fernandez Hospital, Infectious Diseases Unit, Buenos Aires, Argentina.
AUTHOR CONCLUSIONS
A correlation of HCV viral decay in the first 24 h of treatment with PEG-INF/RBV and SVR has been found in our study.
Patients who do not reach 0.9 log10 decay at 24 hours will not achieve SVR, with a very high negative predictive value. These results suggest that in HIV/HCV co-infected patients HCV therapy could be guided following very early changes in HCVVL; allowing to optimize treatment particularly in resource-limited settings, as well as in patients with pretreatment predictors of non-response, or severe toxicity.
ABSTRACT
Background: Treatment with Peg-interferon and ribavirin (PEG-INF/RBV) for HIV/HCV coinfected patients has suboptimal rates of response, with up to 60% of them failing to respond. Virologic response kinetics has emerged as the best prognosis factor of treatment outcome. We have previously reported the correlation of early changes in HCV viral load (HCVVL) and RVR and EVR(1). The aim of this study was to evaluate if HCVVL decay during the first 24 hours predicts treatment outcome.
Methods: Twenty HIV/HCV-coinfected patients on treatment with PEG-INF/RBV, had blood drawn at baseline, 24 h, 4, 12, 24, 48, and 72 wks. HCVVL (Bayer VERSANT HCV RNA 3.0 Assay) and HCV qualitative PCR (Cobas Amplicor HCV 2.0) were evaluated at each time point. Statistical analysis: One way ANOVA and ROC curves.
Results: Nineteen patients were on HAART, LT-CD4: 545 cell/ml (SD 287), 17 males. Metavir F4-F3: 50%. Genotype (Gt) 1: 74%. HCVVL decay at 24 h was statistically significantly higher (p 0.00) among responder patients (1.6 log ± 0.2) than among those who do not respond (0.5 ± 0.4). A decay < 0.9 log in HCVVL at 24 h was determined by ROC curves as the best cut-off that differentiated those non responders patients from responders, exhibiting a negative predictive value of achieving SVR of 100%, and a positive predictive value of 83.3%.
Discussion: A correlation of HCV viral decay in the first 24 h of treatment with PEG-INF/RBV and SVR has been found in our study, patients who do not reach 0.9 log decay at 24 h will not achieve SVR. These results suggest that in HIV/HCV co-infected patients HCV therapy could be guided following very early changes in HCVVL; allowing to optimize treatment particularly in resource-limited settings, as well as in patients with pretreatment predictors of non-response, or severe toxicity.
OBJECTIVES
Since the introduction of HAART, chronic HCV is one of the leading causes of morbidity/mortality in HIV patients (2,3). PEG-INF/RBV is the standard of treatment for chronic HCV infection both in patients monoinfected and coinfected with HIV (4).
Similar response rates have been achieved with PEG-INF alfa 2a and 2b (5). Achieving SVR in 14-36% for Gt1-4 and 43-73% for Gt2-3 (6).
Virological response kinetics has emerged as the best prognostic factor of treatment outcome (7).The typical decline is biphasic, with a rapid first phase lasting of 1-2 days, followed by a second phase less pronounced of HCV RNA decline (8).
The aim of this study was to evaluate if HCV viral load decay during the first 24 hours of treatment with PEG-INF/RBV in HIV/HCV coinfected patients predicts treatment outcome.
METHODS
20 HIV/HCV-coinfected patients on treatment with PEG-INF/RBV,
Blood drawn at baseline, 24 h, 4, 12, 24, 48, and 72 wks. HCV-VL (Bayer VERSANT HCV RNA 3.0 Assay) and HCV qualitative PCR (Cobas Amplicor HCV 2.0) were evaluated at each time point.
Statistical analysis: One way ANOVA and ROC curves.
REFERENCES
1. N.Laufer, et al. HCV kinetic during the first 24 hours of treatment and its relationship with RVR/EVR in HCV/HIV coinfected patients. Poster Discussion: AIDS 2008 - XVII International AIDS Conference: Abstract no. WEPDB204
2. Rockstroh JK, et al. Influence of hepatitis C virus infection on HIV-1 disease progression and response to highly active antiretroviral therapy. J Infect Dis. 2005 Sep 15;192(6):992-1002
3. Weber R, et al. Liver-related deaths in persons infected with the human immunodeficiency virus: the D:A:D study. Arch Intern Med. 2006;166(15):1632-41
4. Chung RT, et al. Peginterferon Alfa-2a plus ribavirin versus interferon alfa-2a plus ribavirin for chronic hepatitis C in HIV-coinfected persons. N Engl J Med. 2004 Jul 29;351(5):451-9.
5. Laguno M, et al. Randomized trial comparing pegylated interferon alpha-2b versus pegylated interferon alpha-2a, both plus ribavirin, to treat chronic hepatitis C in human immunodeficiency virus patients. Hepatology. 2009;49(1):22-31
6. Sulkowski M. Viral hepatitis and HIV coinfection. J Hepatol. 2008;48(2):353-67.
7. Van der eyden,E, et al. Response-guided therapy for chronic Hepatitis C virus infection in patients coinfected with HIV: a pilot trial.CID 2009; 48: 1152-9
8. Dahari, H, et al. Hepatitis C viral kinetics in special populations. Curr Hepat. 2008; 7(3): 97-100.
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