Shocking Latent HIV, Enhancing Immune Defense with a Single Drug

Last month we highlighted the work of scientists from the amfAR Institute for HIV Cure Research at the University of California, San Francisco, and their identification of a new pathway to induce HIV out of its latent state. Such activation renders the virus vulnerable to attack by the immune system. Unfortunately, many of the drugs currently being studied as such latency reversing agents work much better in the test tube than in patients.

  Dr. Ole Søgaard

Dr. Ole Søgaard

Writing in the June issue of the journal Clinical Infectious Diseases, amfAR-funded scientist Dr. Ole Søgaard of Aarhus University in Denmark, with colleagues from there and the University of Copenhagen, joining an international team from Barcelona, Berlin, Belgium, Boston, San Francisco, and Philadelphia, report on an experimental drug with the capacity not only to activate latent HIV, but also to enhance the patient’s innate immune defenses against the activated virus.

Lefitolimod, also known as MGN1703, activates a protein known as TLR9, found on the surface of many types of immune cells. It belongs to a class of agents known as “immune surveillance reactivators,” which induce production of immune hormones, such as interferon-alpha, and enhance the function of dendritic cells, B cells, and natural killer cells. All of these cell types form part of our innate defense against HIV. Lefitolimod is currently in advanced stages of testing in colon cancer patients.

Based on promising studies in the test tube with cells from HIV-infected patients, Søgaard and associates sought to test the drug’s effects in patients themselves.

Fifteen adults taking effective antiretroviral therapy (ART) for at least one year were enrolled in the study. Lefitolimod was injected under the skin twice a week for four weeks. In 40% of the participants, HIV levels dramatically increased, from undetectable (less than 20 copies) to over 1500 copies, consistent with the role of a latency reversing agent. In addition, the researchers observed an enhancement of all immune responses evaluated.

The authors noted that the use of another drug to enhance TLR7, a related immune surveillance reactivator, in monkeys infected with the simian form of HIV also showed promising results, but only when combined with a therapeutic vaccine.

They concluded that their research is “the first clinical trial using a single drug in HIV-1-infected individuals on ART with the aim of both enhancing innate immunity and activating the HIV-1 reservoir.”

Further studies are underway in this promising area of cure research.

Dr. Laurence is amfAR’s senior scientific consultant.