Interferon Alfa Therapy: Toward an Improved Treatment for HIV Infection

Abstract

Highly active antiretroviral therapy(HAART) is an expensive, lifelong treat-ment for human immunodeficiencyvirus (HIV) infection that is associatedwith significant toxicity. Despite advanc-es in treatment, there remains a need fornovel therapies for HIV infection. Onestrategy is to achieve a functional cure,in which treatment can be safely stoppeddespite the presence of residual virus, byfinding approaches that enhance the im-mune response to HIV. Such a therapywould require boosting a patient’sim-mune system to suppress viral replicationbelow clinically relevant levels, therebyeliminating the need for HAART. A ster-ilizing cure, by contrast, is one in whichall functional HIV genomes within thebody are eliminated. Latent HIV genomesrepresent a major barrier to a sterilizingcure because these genomes do notproduce viral proteins and thus cannotbe eliminated by the immune system orby current therapies [1].In this issue, Azzoni and colleaguesassessed the potential of pegylated (Peg)interferon alfa-2a to suppress HIV repli-cation [2]. In what could be a first steptowards a functional cure, they foundthat Peg–interferon alfa-2a permitted asubset of subjects to maintain low viralloads for 12–24 weeks in the absence ofHAART. Furthermore, they found thatin patients with a favorable virologic re-sponse to Peg interferon alfa-2a, levelsof HIV provirus in peripheral bloodmononuclear cells (PBMCs) werereduced. This finding suggests that Peg–interferon alfa-2a may eliminate latentHIV genomes, a possibility that wouldshed light on the search for a sterilizingas well as a functional cure for HIV.Interferon alfa is used clinically forthe treatment of hepatitis B and C virusinfections, and several studies have as-sessed the capacity of this cytokine tolimit HIV replication in vivo [3–9].Mul-tiple studies confirm that interferon alfacan reduce viral load and delay diseaseprogression in viremic patients [3,5–11].However, interferon alfa’s potential tosuppress viremia in patients with well-controlled viral loads is less clear.Recently, one study subjected HAART-treated patients with a viral load of<400 copies/mL forat least 6 months anda CD4