Alpha interferon makes a comeback as HIV treatment

While the corridors of the Hynes Convention Centre in Boston, home to the 10th Conference Retroviruses and Opportunistic Infections, were buzzing with excitement at the prospect of more than a dozen novel antiretrovirals in the pipeline, a hitherto tired, old and familiar friend, interferon, reappeared on Wednesday under a new guise, and with surprising results.

Early in the HIV epidemic, interferon-alpha (IFN-alpha) was found to have activity against HIV in the test tube, but early trials were soon abandoned when easier to take and, at the time, less toxic drugs, like AZT, became available.

Now that IFN-alpha has been improved and reformulated as pegylated interferon-alpha (PEG-IFN-alpha), it can be injected just once a week, and at lower doses than the usual 1.5 micrograms/kg used as the standard of care alongside ribavirin in the treatment of Hepatitis C infection. This makes the drug somewhat more tolerable. A study published in AIDS in 2001 showed that PEG-IFN-alpha had both antiviral and immunostimulating properties in vivo and a report at ICAAC later that year showed that PEG-IFN-alpha reduced viral load by more than 0.5 log, sustained over 12 weeks in individuals on HAART with detectable viral load.

In Wednesday’s presentation from Germany, 10 stable, asymptomatic individuals with no prior therapy and infected with HIV within the past two years (and not co-infected with hepatitis B or C) were randomised to two arms. Those in the treatment arm received low-dose (80 microgram) PEG-IFN-alpha once a week for 24 weeks. Results were reported here to 24 weeks.

The control group, which included two women, lost between 6-176 CD4 T-cells (average decrease from 535 to 450 cells/mm³), and experienced a slight increase in HIV-1 RNA from 3.8 to 4.4 logs.

The on-treatment arm, all of whom were male, gained between 92-208 CD4 cells (average increase from 462 to 611 cells/mm³), and HIV-1 RNA declined between 0.8 and 1.3 logs (average decrease from 4.1 to 3.1 logs).

PEG-IFN-alpha is not without adverse effects, and there were three reports of mild flu-symptoms, three reports of injection site redness and swelling, one report of a more serious injection site reaction, granulomatus, and one report of fatigue. However, there were no lab abnormalities, including no reports of neutropenia (low white blood count), and no reports of depression, which are usually seen at higher doses.

Whilst this pilot study was in recently-infected individuals, PEG-IFN-alpha could potentially be utilised as part of a salvage therapy regimen and is a likely candidate for lengthening the time off standard therapy during Structured Treatment Interruptions. Further studies are currently underway in France and Germany looking at combining PEG-IFN-alpha with HAART.