Hepatitis C viral kinetics during treatment with peg IFN-alpha-2b in HIV/HCV coinfected patients as a function of baseline CD4+ T-cell counts

Abstract

Background: HIV/hepatitis C virus (HCV) coinfected patients are known to have lower sustained viral response (SVR) rates than HCV monoinfected patients. However, the role of CD4+ T-cell counts on viral kinetics and outcome is not fully understood.

Methods: HCV RNA kinetics (bDNA v3, lower limit of detection [LD] = 615 IU/mL) was analyzed in 32 HIV/HCV coinfected persons treated with Pegylated-interferon-alpha2b (1.5 microg/kg weekly) and ribavirin (1-1.2 g daily) for 48 weeks and compared with results obtained from 12 HCV monoinfected patients treated with the same regimen.

Results: Baseline CD4+ T-cell counts > or =450 cells/mm3 were significantly (P < 0.002) associated with SVR in coinfected genotype 1 patients. First phase decline was significantly lower among patients with low as compared with high CD4 counts (P < 0.03) and among coinfected compared with monoinfected patients (P < 0.002). Second phase decline slope showed a similar trend for coinfected patients.

Conclusions: Low baseline CD4+ T-cell count is associated with slower HCV viral kinetics and worse response to treatment among HIV coinfected patients, suggesting HCV treatment response depends on immune status. HCV genotype 1 coinfected patients have slower first phase viral kinetics than HCV monoinfected patients. First phase viral decline (>1.0 log) and second phase viral decline slope (>0.3 log/wk) are excellent predictors of SVR for coinfected patients.

Conflict of interest statement

Conflict of Interest Statement

None of the other authors have any conflicts of interest to report.

Figures

Figure 1. HCV response to treatment is associated with high baseline CD4+ T cell counts in HIV/HCV co-infected patients

HCV genotype 1 patients co-infected with HIV that have baseline CD4+ T cell counts < 450 cells/mm3 show 0% SVR and ETR, while those with baseline CD4+ T cell counts ≥ 450 cells/mm3 show significantly (P=0.002) higher ETR (76%) and SVR (29%). The same trend is found for HCV genotype 2 patients. NR-non response, VB-viral breakthrough, REL- end-of-treatment response with relapse, SVR-sustained viral response.

Figure 2. HCV kinetics as function of baseline CD4+ T cell counts and of HCV genotype in patients co-infected with HIV

Co-infected patients with HCV genotype 1 show significantly (P+ T cell counts < 450 cells/mm3 show slower decline than do patients with higher baseline CD4+ T cell counts (* for genotype 1 patients P<0.03 in days 3, 28–84). Dashed horizontal line represents LOD-limit of detection (<615 IU/mL).

Figure 3. First phase decline and 2nd phase slope as function of CD4+ Tcell count and genotype in co-infected patients versus mono-infected patients

Among co-infected patients, those with baseline CD4+ T cell counts < 450 cells/mm3 had significantly lower 1st phase decline (P<0.03) and a trend for slower 2nd phase decline slope than patients with higher CD4 counts. Moreover, mono-infected patients had significantly (P<0.02) faster 1st phase decline than co-infected patients, but non-significantly different 2nd phase decline slope (within the first 28 days). Co-infected genotype 2–3 patients had faster viral kinetics than genotype 1 patients, similar to genotype 2–3 mono-infected patients. ND: end-point not determined.