Remission Achieved in Simian Form of HIV

Monkeys infected with SIV were successfully able to suppress SIV even without antiretroviral therapy.

Monkeys infected with SIV, the simian form of HIV, recently achieved remission due to an experimental treatment involving antiretroviral therapy and an antibody. The experimental treatment has also restored a majority of the immune cells the infection eradicated, which antiretroviral therapy (ART) is unable to do.

Suppression was observed for as long as 23 months since completing the treatment, according to a press release from the National Institutes of Health, which conducted the study along with Emory University.

“Our data suggest that the immune systems of these animals are controlling SIV replication in the absence of antiretroviral therapy,” said co-leader of the study Anthony S. Fauci, MD. “The experimental treatment regimen appears to have given the immune systems of the monkeys the necessary boost to put the virus into sustained remission. The precise mechanisms of this effect are unclear and will be actively pursued since they could have important implications for the control of HIV infection in humans in the absence of ART. At this point it is also unclear whether the findings of the newly reported animal study will translate into a clinical benefit for HIV-infected people.”

In the study, 18 rhesus macaques were infected with SIV. After 5 weeks of infection, the monkeys received 90-days on antiretroviral therapy.

After 9 weeks, 11 monkeys received infusions of an antibody every 3 weeks for 23 weeks. The laboratory-derived monkey antibody against the a4b7 integrin cellular receptor is similar to vedolizumab, a drug that treats ulcerative colitis and Crohn’s disease, according to the press release.

The other monkeys included in the study received placebo infusions. All treatment stopped at 32 weeks after infection.

Scientists discovered that all 18 monkeys suppressed HIV by week 3 on antiretroviral therapy. They also found that after stopping treatment, the SIV levels in the control group increased.

The monkeys who received the experimental infusions also rebounded to high levels of SIV, but regained control within 4 weeks, while some never rebounded. These monkeys continued to suppress their infection in both blood and gastrointestinal tissues for 23 months, according to the study.

Antiretroviral therapy suppresses HIV/SIV to undetectable levels, but the virus may still be in the genetic material of infected immune cells, even when suppressed. If treatment with antiretroviral therapy is stopped, viral levels will rebound within in weeks due to genetic materials in viral reservoirs.

This requires that patients with HIV must take antiretroviral therapy daily for the rest of their lives, which may be challenging to adhere to, and may have long-term side effects.

“The new findings suggest an alternative form of HIV therapy that may eliminate a requirement for lifelong daily ART, potentially improving the quality of life for people living with the virus and reducing the staggering, unmet cost of antiretroviral therapy for the 37 million people worldwide who need it,” said senior author of the study Aftab A. Ansari, PhD.

Veolizumab is an antibody to the a4b7 integrin receptor, which is present in high levels on the immune cells infected with HIV/SIV, according to the press release. The purpose of the antibody is to prevent immune cells from going to gastrointestinal tissues where HIV/SIV replicate and viral reservoirs form.

However, the mechanism behind the antibody’s regulation of SIV replication is still unknown.

“If we could figure out how the antibody works, then an effective HIV vaccine could be modeled on that mechanism,” Dr Ansari said. “That is the most important implication of our findings.”

While it is unclear if these findings will translate to humans, the scientists have taken steps to find out in a small clinical trial that tests whether a 30-week course of vedolizumab is safe, tolerable, and can suppress HIV without antiretroviral therapy. The results are expected by the end of 2017, National Institutes of Health concluded.