Hepatitis C therapy with interferon-α and ribavirin reduces CD4 T-cell-associated HIV-1 DNA in HIV-1/hepatitis C virus-coinfected patients

Abstract

Combined treatment with interferon alpha (IFN-α) and ribavirin (RBV) can effectively cure HCV infection in a significant proportion of patients, but effects of this regimen on cellular reservoirs for human immunodeficiency virus type 1 (HIV-1) are unknown. Here, we show that treatment with IFN-α/RBV led to a moderate but significant and sustained decline of HIV-1 DNA in CD4 T cells from HIV-1/hepatitis C virus-coinfected patients receiving highly active antiretroviral therapy (n = 12). However, in vitro experiments failed to demonstrate an effect of pharmacological doses of IFN-α on HIV-1 reactivation. Together, these data suggest that treatment with IFN-α/RBV can moderately reduce the reservoir of HIV-1-infected CD4 T cells that persists despite suppressive antiretroviral therapy.

Keywords: HIV-1 reservoir; HIV-1/HCV coinfection; interferon-α; ribavirin.

Figure 1.

Reduction of CD4 T-cell–associated human immunodeficiency virus type 1 (HIV-1) DNA during interferon alpha (IFN-α)/ribavirin (RBV) treatment in HIV-1/hepatitis C virus (HCV)–coinfected patients. A, Time intervals during which changes in HIV-1 DNA were evaluated in HIV-1/HCV-coinfected patients. B–D, Changes in total (left panels) and integrated (right panels) HIV-1 DNA in CD4 T cells from HIV-1/HCV-coinfected study patients during time intervals I (B), II (C), and III (D). Amplification of integrated HIV-1 DNA was unsuccessful in 2 study subjects. Patient 1: ; Patient 2: ; Patient 3: ; Patient 4: ; Patient 5: ; Patient 6: ; Patient 7: ; Patient 8: ; Patient 9: ; Patient 10: ; Patient 11: ; Patient 12: . E, Fold change of HIV-1 DNA in indicated time intervals. Data reflect median and range. F, Inverse association between maximum CD4 T-cell changes during HCV therapy and corresponding absolute and relative changes in CD4 T-cell–associated integrated HIV-1 DNA. Spearman correlation coefficients are shown. G, Analysis of HIV-1 RNA and total or integrated HIV-1 DNA in primary CD4 T cells from highly active antiretroviral therapy–treated patients after in vitro exposure to IFN-α, IFN-α + RBV, or panobinostat. *P = .06 in comparison to untreated control. H, IRF7 mRNA expression in CD4 T cells after in vitro exposure to IFN-α, RBV or IFN-α + RBV.