An article published last week in PLoS Pathogens argues that combining antiretroviral therapy with a short course of immunotoxins, which are used in certain types of chemotherapy, could suppress HIV levels to the point that antiretrovirals are no longer needed long-term.

“Ultimately, immunotoxins will be of value in HIV treatment only if they can enable patients to stop HAART for prolonged periods, sufficient to provide a meaningful quality of life benefit,” wrote the authors.

Although still preliminary, the authors believe the idea is promising enough that it should be tested in clinical trials.

The major problem with highly active antiretroviral therapy (HAART) is that it does not completely eliminate the virus from the body.

Infected cells, called “reservoirs,” hold HIV in a dormant state. Although HAART prevents new cells from being infected, it cannot kill cells that are already infected by HIV.

As soon as HAART is stopped, the virus starts multiplying again and the infection spreads.

Over the past two decades, research groups at the National Institutes of Health have focused on developing treatments to kill the infected cells. These cells can be identified by the presence of a virus protein, called Env, on their surface.

Immunotoxins, which have been used successfully to treat a certain type of leukemia, can be designed to recognize Env and kill infected cells that display the protein.

Previous Phase 1 clinical trial results with immunotoxins in the pre-HAART era were disappointing; no antiviral or immune-enhancing effects were observed at the maximum tolerated dose, which was below the typical dose for cancer immunotoxins.

The dosage could not be increased at that time because of possible liver toxicity.

Since then, however, the authors have created a new immunotoxin that is more powerful and less toxic. So far it has only been studied in the lab.

The authors suggest that now, with the development of HAART, these Env-targeted immunotoxins may work significantly better than they did in the earlier clinical trials.

In laboratory tests in combination with HAART, the immunotoxins were able to keep HIV levels low even 30 days after HAART was stopped; without the immunotoxins, virus levels had already rebounded 30 days after HAART was stopped.

“These results highlight the particular value of combining HAART drugs, which potently block HIV replication, with Env-targeted toxins, which kill cells that are already infected,” wrote the authors.

If these results are verified in clinical trials, it could mean that people diagnosed with HIV would receive a combination of HAART and immunotoxins only temporarily, rather than having to take HAART their entire lives to ensure virus suppression.

As a result, the authors argue that “the time has come” for clinical trials to evaluate Env immunotoxins as complement therapy with HAART in treating and eradicating HIV.

Dr. Edward Berger, lead author on the paper, discussed plans for future trials with The AIDS Beacon.

“We hope to get 3B3-PE38 [a new immunotoxin] into Phase 1 clinical trials, and are in process with the FDA. It would be given only to infected people whose viral loads have been greatly suppressed by [antiretrovirals], and the [antiretrovirals] would continue during the short period (1-2 weeks) of immunotoxin treatment.”

Dr. Berger also thought the treatment could have some limited potential in post-exposure prophylaxis. Post-exposure prophylaxis is treatment given to someone who has been exposed to HIV, and can help prevent the infection from taking hold.

“Post-exposure prophylaxis is a realistic consideration, but only if administered on one or two occasions. The reason is that the PE38 [immunotoxin] portion of the [treatment] is of bacterial origin, and thus would be recognized as ‘foreign’ by the immune system, leading to production of antibodies that would neutralize the activity of the [immunotoxin]. Hence regular use for prevention would not be feasible.”

For more information, please see the study on the PLoS Pathogens website.