amfAR, The Foundation for AIDS Research

Possible New Use for an Old Antiviral Drug in Attacking Latent HIV

By Jeffrey Laurence, M.D.

Dr. Mathias Lichterfeld.jpgDr. Mathias LichterfeldOne of the very first things to be tried as a potential therapy for AIDS, first in the test tube and then in people infected with HIV, was the “universal” antiviral agent known as alpha-interferon. It had a modest effect, reducing levels of virus by at most 80–90%, compared to the more than 99.99% reduction that can be obtained by standard antiretroviral therapy (ART).

Alpha-interferon is much more potent in treating hepatitis C virus (HCV)—when used in combination with another drug, ribavirin. But a couple of years ago interferon use was resurrected during experimental treatments directed at an AIDS cure. It was found that it could target T cells harboring dormant or latent HIV. Regular readers of these bulletins will recognize these cells as a key impediment to eradicating HIV.

Writing in the May issue of the Journal of Infectious Diseases, amfAR-funded scientist Mathias Lichterfeld of Massachusetts General Hospital and colleagues from China, Denmark, and Spain confirmed and extended the initial observation of interferon and its effect on HIV reservoirs. They studied a population of HIV-positive individuals who were well-controlled on ART but co-infected with HCV and therefore required additional treatment with interferon and ribavirin.

Lichterfeld and colleagues found that T cell-associated total and integrated latent HIV DNA declined by half during the period of interferon and ribavirin administration. And it was not simply due to the non-specific killing of more T cells. Rather, the cells harboring HIV were selectively targeted. It was also not due to a “shock and kill” effect, by which interferon induced HIV to grow, only to be killed by ongoing ART. Neither interferon alone, nor in combination with ribavirin, could do this in the test tube.

The authors admit that the 50% reduction in latent virus seen here is unlikely to be clinically significant. A thousandfold reduction in HIV DNA or more will probably be necessary. What this pilot study did provide was an insight into a potential new strategy for attacking HIV reservoirs, based on knowledge of the pathways that interferon might use to alter HIV DNA. They conclude, “Further investigation may be helpful for designing improved clinical strategies to target HIV-1 reservoirs that persist despite HAART [highly active antiretroviral therapy].”

Dr. Laurence is amfAR’s senior scientific consultant.