A clinical trial testing infusions of combination antibodies in people living with HIV has begun at the National Institutes of Health. The early phase clinical trial will evaluate whether periodic infusions of two highly potent, HIV-specific, broadly neutralizing antibodies (bNAbs)-3BNC117 and 10-1074-are safe in people living with HIV. The study also will gather preliminary data on how effectively the bNAb infusions, delivered together every two to four weeks, suppress HIV following discontinuation of antiretroviral therapy (ART).
“Antiretroviral therapy suppresses HIV to very low levels, normalizes life expectancy, and prevents sexual transmission of the virus. However, these benefits are lost if an individual stops taking the medications as prescribed,” said Anthony S. Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases (NIAID), part of NIH. “If proven safe and effective, periodic infusions of potent, broadly neutralizing HIV antibodies may be a potential alternative to daily antiretroviral therapy.”
The new Phase 1 trial is being led by Michael C. Sneller, MD, and Tae-Wook Chun, PhD. Sneller is a medical officer in the NIAID Laboratory of Immunoregulation (LIR), and Chun is chief of LIR’s HIV Immunovirology Unit.
In 2016, Drs. Sneller and Chun and their collaborators found that the anti-HIV bNAb VRC01 could be safely delivered to people living with HIV, though it had only a modest effect on controlling HIV in the absence of ART. They found that the effect was modest because the virus quickly mutated in some individuals such that the antibody could no longer neutralize HIV. The two bNAbs used in the current study bind to distinct regions on an HIV surface protein, preventing the virus from entering and infecting cells. These regions are conserved, meaning they remain the same across most HIV strains. Targeting two conserved regions on the virus may reduce the risk of resistance.
“When we first began developing antiretroviral medications more than two decades ago, we found that HIV mutated to escape the effect of any single drug acting alone,” said Sneller. “However, we had remarkable success treating people with combinations of drugs, which targeted different parts of the HIV replication cycle,” he added. “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.”
The 3BNC117 and 10-1074 bNAbs were developed by Michel Nussenzweig, MD, PhD, and colleagues at Rockefeller University, New York City, with support from NIH and the Bill & Melinda Gates Foundation. The bNAbs have shown promise in nonhuman primates infected with the simian form of HIV.
The NIH study will enroll two groups of volunteers: 30 people who began ART during early HIV infection and who are still taking ART, and about 15 individuals whose HIV infections seem to be advancing at an abnormally slow rate even though they have never taken ART. Among the first group, 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 eight infusions of the combination antibodies or placebo over 24 weeks. Participants will be closely monitored and will be restarted on ART if HIV levels in their blood rise above 1,000 copies per milliliter, if there is a significant decline in levels of their protective immune cells called CD4+ T cells (link is external), or if they develop any HIV-related symptoms. All volunteers in the second group, known as “slow progressors,” will receive the combination antibody infusions on the same schedule but will remain without ART throughout the study unless they experience a significant decline in CD4+ T cells, sustained increase in HIV levels in their blood, or an opportunistic infection. Researchers will monitor both groups closely for any side effects or other adverse events. Results are expected in 2021.
Nussenzweig and Marina Caskey, MD, at Rockefeller University, are conducting a related and ongoing NIAID-supported trial evaluating the safety of infusions of the same two bNAbs in people living with long-term HIV infection. Their study will enroll approximately 40 individuals, and results are expected in 2022.
Source: National Institutes of Health (NIH)
Dear Helpdesk: Working in a Toxic Health Care Environment
March 28th 2024Dear Helpdesk is your steadfast companion, offering life coaching and workplace advice from 2 seasoned IPs for some of your most challenging real-life situations. Let us help you navigate the intersection between work and life, guiding you to navigate the dynamic world of infection prevention with confidence and grace. This article is on handling a toxic health care environment.
Product Locator: Spring and Early Mother's Day Gift Guide for Infection Prevention Personnel
March 27th 2024Whether it's a spring holiday, birthdays, or no reason at all, infection prevention personnel love to give and receive gifts that help at the end of a stressful day. Infection Control Today® offers some gift ideas for infection prevention personnel and their families.
Catching Up With Vangie Dennis, AORN 2022-2023 President at AORN 2024
March 26th 2024Infection Control Today (ICT) had the privilege of catching up with Vangie Dennis, MSN, RN, CNOR, CMLSO, at the Association of periOperative Registered Nurses' (AORN’s) International Surgical Conference & Expo 2024. As the former president of AORN and an esteemed figure in perioperative services, Vangie Dennis shared insights into her recent endeavors and the exciting new chapter she's embarked upon.
How To Optimize Your Time Management Strategies for the Busy Infection Preventionist
March 25th 2024Is your calendar resembling a chaotic masterpiece of overlapping tasks? Join the club of infection preventionists striving to balance responsibilities. Dive into proven strategies from a fellow infection preventionist to reclaim control of your time, streamline tasks, and boost productivity effectively. This is an IP Lifeline article.