Broadly Neutralizing Antibody Sparks Treatment-Free HIV Remission

A combination therapy that attacks the viral reservoir may be crucial to controlling HIV replication without medication.

In addition to traditional antiretroviral therapy (ART), an experimental combination of a broadly neutralizing antibody (bNAB) and an immune stimulatory compound resulted in HIV suppression for 6 months without treatment in monkeys, according to a press release from the National Institutes of Health.

The study was funded in part by the National Institute of Allergy and Infectious Disease (NIAID) and presented at the 25th Conference on Retroviruses and Opportunistic Infections.

The authors hypothesize the new treatment may target the HIV viral reservoir, which is the key to prevent viral replication in the absence of ART.

The study results may inform approaches to achieve drug-free remission in humans with HIV, according to the release.

“HIV excels at evading the immune system by hiding out in certain immune cells. The virus can be suppressed to very low levels with antiretroviral therapy, but quickly rebounds to high levels if a person stops taking medications as prescribed,” said Anthony S. Fauci, MD, NIAID director. “The findings from this early stage research offer further evidence that achieving sustained viral remission without daily medication might be possible. This potential application is yet another example of how the research community is using powerful, broadly neutralizing antibodies in multiple experimental applications to protect against and treat HIV.”

Included in the study were 44 rhesus macaques with simian human immunodeficiency virus who were administered ART to elicit viral suppression. Monkeys continued to use ART throughout the experimental therapy and for an additional 16 weeks.

After 96 weeks of ART, the monkeys were divided into 4 groups: a cohort administered 5 infusions of the bNAB, PGT121; a cohort that received 10 administrations of an investigational immune stimulant, GD-9620; a cohort administered both treatments; and a control cohort, according to the release.

The goal of the trial was to determine whether the antibody-immune stimulant combination could curb viral replication compared with ART.

Following ART discontinuation, all 11 control monkeys experienced viral rebound after a median of 21 days compared with 6 out of 11 monkeys in the combination therapy cohort that experienced viral rebound after a median of 112 days, according to the release.

Despite the viral rebound, the monkeys in the combination group had viral loads more than 100-fold lower than the control group. These animals were also observed to have less viral DNA in their lymph nodes, which suggests the viral reservoir was reduced, the authors noted.

Notably, adding GS-960 was observed to extend the length of viral suppression and drastically reduce the viral reservoir, according to the release.

Further studies that examine the action of GS-960 and those that explore strategies that expand on this action could help researchers reduce viral reservoirs in humans with HIV, according to the release. The goal would be to suppress HIV without daily treatment.

“Our findings suggest that the development of interventions to activate and eliminate a fraction of the viral reservoir might be possible,” said principal investigator Dan Barouch, MD, PhD. “Although we are still a long way off from having a cure for HIV, our data suggest a strategy for targeting the viral reservoir that can be further explored.”