HCV RNA decline in the first 24 h exhibits high negative predictive value of sustained virologic response in HIV/HCV genotype 1 co-infected patients treated with peginterferon and ribavirin

Abstract

Background: Treatment with Peg-interferon and ribavirin (PEG-IFN/RBV) for HIV patients co-infected with hepatitis C virus (HCV) genotype 1 has suboptimal rates of response. Viral kinetics has emerged as one of the best prognostic factors of treatment outcome.

Methods: Twenty HIV/HCV genotype 1 co-infected patients in treatment with PEG-IFN/RBV, had blood drawn at baseline, 24 h, 4, 12, 24, 48, and 72 weeks. HCV-RNA levels were evaluated at each time point. ROC curves were used to evaluate the log10 HCV-RNA decay at 24 h that exhibits the best predictive value of achieving response. Genomic characterization of HCV NS5A at both interferon sensitivity-determining region (ISDR) and protein-kinase binding (PKRBD) domains were performed in order to evaluate its heterogeneity and association with 24 h HCV-RNA decay and SVR.

Results: Non-responder patients exhibited a mean of 0.7 log10 (SD 0.74 log10) HCV-RNA decay at 24 h, whereas responder-patients presented 1.6 log10 (SD 0.28 log10), p = 0.04. A reduction in HCV viral load from baseline to 24 h of < 1.4 had a negative predictive value for achieving SVR of 100% and a positive predictive value of 50%. HCV genotype 1 isolates from patients with a decrease of HCV-RNA at 24 h > 1.4 log10, exhibited 3.1(SD 1.5) amino acids substitutions in ISDR and 4.8(SD 2.3) in PKRBD regions and 1.6(SD 0.7) and 2.4(SD 1.3), respectively, in those patients presenting lower reduction in HCV-RNA.

Conclusions: HIV/HCV genotype 1 co-infected patients with a decrease in HCV-VL at 24 h > 1.4 log10 are more likely to achieve SVR when treated with PEG-IFN/RBV than those with lower levels of HCV-RNA decay. Along with other host-related and viral-related prognostic factors in HIV/HCV co-infected patients, this very early time point of evaluation could be of relevance in the management of HCV-specific treatment.

Figure 1

HCV 24h viral load decrease (median and range) according to the achievement of RVR, EVR (complete and partial), SVR and null response (NR). cEVR: complete early virological response; pEVR: partial early virological response; RVR: rapid virological response; NR: null response

Figure 2

HCV viral load kinetics during treatment with PEG-IFN/RBV divided by viral response. SVR: sustained virological response. No SVR: absence of sustained virological response.

Figure 3

Area under the receiver operating characteristic curve, to evaluate the performance of HCV-RNA log₁₀ decay at 24h with sustained virological response as the state variable.

Figure 4

Basal HCV ISDR and PKRBD amino acids sequences of 19 HCV-HIV co-infected patients. Patients 6, 13 and 14 were SVR, and 1, 2, 3, 4, 5, 7, 8, 9, 10, 11, 12, 15, 16, 17, 18 and 19 were NR. M62321 were used as references sequences to compare mutations. HCV-J (D90208) also was included.