THE NEW EPIDEMIC HIV/HCV CO-INFECTION Part 5
Pegylation: Improving the action of alpha interferon
Newer forms of alpha interferon using “pegylation” have been developed. The term pegylation comes from polyethylene glycol (PEG), a substance that, put very simply, changes the way another substance is metabolized.
Attaching PEG to alpha interferon leads to a longer half-life of the interferon because it is cleared more slowly by the kidney. Since pegylation of alpha interferon lengthens the time it takes the body to clear the drug, it results in a more desirable (longer) sustained viral response, or SVR. The goal of this new technology is to attain a better end of treatment (EOT) result. More specifically, the present EOT goal is to eradicate HCV for the year following a 6-month to year-long period of treatment.
The pegylated alfa interferons, soon available from two pharmaceutical companies (Roche and Schering) require only once-weekly subcutaneous injections. The greater convenience should result in much better compliance among people being treated for HCV. Pegylated interferon alpha will also improve outcomes by slowing the metabolism of interferon alpha.
Does alpha interferon hold wider promise as an antiviral treatment? Recently, a physician posed this question to Medscape’s “Ask the Expert…” column: “Is there any role for interferon in HIV management in the absence of hepatitis C coinfection? The medical director of my clinic has decided to add low-dose interferon (approximately 30,000 U SC every week) to the patients’ HAART/IL-2 regimen.” The expert responded that, indeed, some studies have suggested that interferon-alpha has a modest antiretroviral effect, but its limitations-unwanted side effects, inconvenient administration, and attenuation of the CD4+ response-would no doubt prevent it from becoming a mainstay of HIV treatment. However, a role for the pegylated form of IFN-alpha might arise in the future, in particular for patients who are failing HAART.18
Other treatments being considered to treat HCV in coinfected people include HCV protease and helicase inhibitors, antisense oligonucleotides and ribosomes, induction, and liver transplantation.
Treating HCV with standard regimens of alpha interferon alone does not appear to improve the outcomes of coinfected people. People using ribavirin with interferon alpha appear to have better outcomes.
Current treatments for either HIV or HCV cause multiple side effects and drug interactions, and the dosing regimens remain burdensome for most patients. These problems are at least doubled in aggressive treatment of coinfected patients. As one HIV expert put it,3
It is still not clear…exactly how the determination for treatment should be made. Although there can be substantial toxicities, the potential to eradicate infection would seem to support a very aggressive approach.
-William O’Brien, MD