Phase 1 Clinical Trial Set to Evaluate Broadly Neutralizing Antibodies for Safety in HIV Patients

Antiretroviral therapy (ART) has become the standard of treatment used to suppress HIV to low levels and decrease the likelihood of sexual transmission of the virus. However, the benefits of ART are dependent on if patients adhere to their prescribed treatment regimens.

Now, in a new phase 1 clinical trial sponsored by the National Institutes of Health, investigators are evaluating whether it is safe to administer infusions of 2 broadly neutralizing antibodies (bNAbs) in people living with HIV.

“If proven safe and effective, periodic infusions of potent, broadly neutralizing HIV antibodies may be a potential alternative to daily antiretroviral therapy,” Anthony Fauci, MD, director of the NIH’s National Institute of Allergy and Infectious Diseases (NIAID), said in a recent statement.

The bNAbs being assessed—3BNC117 and 10-1074—were developed at Rockerfeller University by Michel Nussenzweig, MD, PhD, and other investigators with support from the NIH and the Bill & Melinda Gates Foundation. These bNAbs have already demonstrated promise in trials with nonhuman primates infected with the simian form of HIV.

The new study will be led by Michael C. Sneller, MD, medical officer in the NIAID Laboratory of Immunoregulation (LIR) and Tae-Wook Chun, PhD, chief of LIR’s HIV Immunovirology Unit. The intention of the study will be to determine if the bNAbs are safe, as well as gather preliminary data on the effectiveness of the infusions delivered together at various time periods to suppress HIV following the discontinuation of ART.

In 2016, Drs. Sneller and Chun discovered that the bNAb VCR01 was able to be safely delivered to people living with HIV. However, the investigators also found that the effect was modest in the absence of ART because the virus was able to mutate quickly, inhibiting the antibody’s ability to neutralize HIV.

“We had remarkable success treating people with combinations of drugs, which targeted different parts of the HIV replication cycle,” said Dr. Sneller, “Our group hypothesized that a combination approach to infusions of broadly neutralizing antibodies might also help avoid the development of resistance that has been observed following treatment with individual bNAbs.”

In the new phase 1 trial, the investigators are using 2 bNAbs that bind to specific regions on the HIV surface protein and can prevent the virus from entering and infecting cells. The regions were selected because they remain the same across most strains of HIV. By targeting 2 regions, the risk of resistance may be reduced.

This study will enroll about 45 individuals into 2 volunteer groups: 30 individuals who began ART during early HIV infection and who are still taking ART and about 15 individuals who have never taken ART and whose HIV infections seem to be advancing at an abnormally slow rate.

In the first group, the volunteers will stop taking ART a few days after being assigned at random to receive either infusions of the combination antibodies or a saline placebo; this group will receive a total of 8 infusions of the combination antibodies or placebo over the course of 24 weeks.

Investigators will closely monitor the participants, who will be restarted on ART if HIV levels in their blood rise above 1,000 copies per ML, if there is a significant decline in levels of their CD4+ T cells, or if they develop any HIV-related symptoms.

All volunteers in the second group will receive the combination antibody infusions on the same schedule but will remain without ART throughout the study unless they experience a severe decline in CD4+ T cells, an increase in HIV levels in their blood, or an infection.

Both groups will be monitored closely for any side effects or adverse events that may occur.

Trial results are expected in 2021.

Another NIAID-supported study is also being conducted by investigators at Rockefeller University, which is evaluating the safety of infusions of the same 2 bNAbs in people living with long-term HIV infection. This study will enroll 40 individuals and results are expected in 2022.