Short-term Treatment With Interferon Alfa Diminishes Expression of HIV-1 and Reduces CD4⁺T-Cell Activation in Patients Coinfected With HIV and Hepatitis C Virus and Receiving Antiretroviral Therapy

Abstract

Long-term treatment with interferon (IFN) alfa plus ribavirin decreases the proviral human immunodeficiency virus type 1 (HIV) DNA level. However, the short-term impact of IFN alfa on persistent HIV and its effects on immune activation after antiretroviral therapy remain unknown. Our study showed that the cell-associated HIV RNA level and CD4(+) T-cell activation decreased in the IFN group (n = 10). No changes were detected in levels of residual plasma viremia, replication-competent reservoirs, proviral DNA, or 2-long-terminal repeat circles, although APOBEC3G, TRIM5α, BST2, and TRIM22 were upregulated in the IFN group. These data suggest that short-term treatment with IFN alfa combined with RBV decreases HIV expression, in part through inhibition of HIV transcription by TRIM22 and decrease in T-cell activation.

Short-Course Toll-Like Receptor 9 Agonist Treatment Impacts Innate Immunity and Plasma Viremia in Individuals With Human Immunodeficiency Virus Infection

“…Thus, we report the first in vivo evidence that a single drug may both enhance immunity and increase HIV-1 transcription. IFN-α is essential for immunological control of HIV infection (eg, by induction of antiretroviral restriction factors) [27,28], and studies have demonstrated that long-term treatment with exogenous IFN-α can lead to viral suppression and a decline in integrated HIV-1 DNA [29], total HIV-1 DNA [30], and CA-US HIV-1 RNA [31]. We observed increased levels of IFN-α2 and a significant upregulation of numerous ISGs.…”

Current views on interferon therapy for HIV

“…Several studies have suggested that long-term IFN-alpha therapy could reduce the size of the HIV reservoir [44][45][46][47]. Azzoni et al [44] conducted a proof-of-concept clinical trial designed to establish that IFN-alpha could suppress HIV replication in subjects where it was already partly controlled by HAART.…”

“…However, after discontinuation of IFN-alpha, HIV DNA returned to baseline levels. Finally, Moron-Lopez et al [47], performed an open, prospective, nonrandomized study to evaluate the impact of IFN-alpha on the HIV reservoir; included were 21 HIV/HCV coinfected patients who had been receiving suppressive HAART for at least 6°m onths at enrollment. Ten patients started HCV therapy with Peg-IFN-alpha-2a and RBV, while HCV therapy was deferred (control group) for the remaining 11 patients.…”

Interferon Alpha Subtype-Specific Suppression of HIV-1 InfectionIn Vivo

“…While IFN-␣2 is efficacious in the treatment of HBV and HCV, HIV-1 studies have shown much less promise (23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34). However, encouraging results from recent clinical studies (23,26,35) and new discoveries demonstrating IFN-␣ induction of antiretroviral restriction factors have led to a renewed interest in IFN-␣ therapy. IFN-␣ and antiretroviral (ARV) drugs work via different mechanisms, and IFN-␣'s unique capacity to reduce the proviral load combined with ARV therapy could lead to a functional cure for HIV-1.…”