Interferon-α Produces Significant Decreases in HIV Load

Abstract

A randomized, controlled clinical trial was started in the pre-HAART era to compare the efficacy of zidovudine (AZT) and interferon-alpha (IFN-alpha) either alone or in combination to reduce HIV viremia, maintain CD4(+) cell count, and decrease time to AIDS progression and death. The purpose of the current study was to compare the effects of AZT and IFN on HIV load using modern technology. One hundred and eighty patients with CD4(+) counts above 500 cells/mm(3) were randomized to receive AZT alone, IFN-alpha alone, or AZT and IFN-alpha in combination. CD4(+) cell count and HIV load at baseline and at the last follow-up visit were compared, and time to AIDS or death was calculated by treatment group. At a mean follow-up of 45 weeks, the mean change in log HIV RNA was -0.06 for the AZT alone group, -0.47 for the AZT plus IFN-alpha group (P = 0.01 versus AZT group), and -0.35 for the IFN-alpha alone group (P = 0.02 versus AZT group). There was no significant difference among groups in change in total CD4(+) count or in time to AIDS or death. Since treatment with IFN-alpha produces significant decreases in HIV load, additional studies of IFN-alpha as part of a combination regimen are warranted.

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

“…Although therapy of HIV-1 patients with IFN-␣2 has produced decreases in viremia in some studies (24)(25)(26)(27)(28)(29)(30)(31), the use of IFN-␣2 has been based more upon its availability as a pharmaceutical-grade protein and its efficacy in treating HCV and HBV infections than upon evidence that it is the most efficacious subtype against HIV-1. Recent in vitro work (14), combined with these new in vivo results, suggest that, based on differential expression patterns, restriction factor induction, mobilization of immune effectors, and ultimate anti-HIV-1 potency, not all subtypes play redundant roles in HIV-1 infection, and therefore, they should be individually evaluated as anti-HIV-1 therapeutics.…”

“…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.…”

Characterization of the Alpha Interferon-Induced Postentry Block to HIV-1 Infection in Primary Human Macrophages and T Cells

“…For instance, though the levels of IFN-␣ and other proinflammatory cytokines are elevated during acute infection (100), perhaps serving to repress initial viral expansion and spread, higher levels of serum IFN-␣ during chronic infection seem to correlate with higher viral loads and a more rapid disease progression (57,105,114,124). Nevertheless, a small number of clinical trials with HIV-1-infected individuals have reported decreases in the viral load following treatment with exogenous IFN-␣ (1,5,41,106), indicating that our understanding of the interplay between type I IFN and HIV-1 is somewhat rudimentary and deserving of further attention.…”

A Variant Macaque-Tropic Human Immunodeficiency Virus Type 1 Is Resistant to Alpha Interferon-Induced Restriction in Pig-Tailed Macaque CD4+T Cells

“…The significance of the IFN response for controlling HIV-1 or SIV infection in vivo has remained unclear because IFN-I expression is elevated during acute infection and high levels of IFN-␣ during chronic infection typically correlate with high viral loads and rapid disease progression, suggesting that it may hasten disease (1,4,8,9). However, some clinical trials with HIV-1-infected individuals have reported decreases in viral load following treatment with exogenous IFN-␣, indicating that IFN-I responses may present a barrier to HIV-1 replication (10)(11)(12). Thus, the role of IFN-I responses in HIV-1 infection and disease remains poorly understood.…”