PAUSE Study Is Evaluating two Long-Acting Broadly Neutralizing Antibodies
Los Angeles, Calif. – ACTG, a global clinical trials network focused on HIV and other infectious diseases, today announced the opening of the PAUSE study (Pausing Antiretroviral Treatment Under Structured Evaluation, also known as A5416/HVTN 806/HPTN 108), the first ACTG HIV cure clinical trial to take place on the African continent. PAUSE is a phase 1, double-blind, randomized study evaluating the safety and efficacy of the two long-acting broadly neutralizing antibodies (bNAbs) 3BNC117-LS-J and 10-1074-LS-J, compared to placebo in adults living with HIV who discontinue antiretroviral therapy (ART) during a closely monitored treatment pause (known as an analytic treatment interruption).
While current ART can manage HIV very well, it does not cure it. People living with HIV have to take ART for the rest of their lives in order to suppress viral replication and protect their immune systems. Even when taking ART, people living with HIV have latent HIV reservoirs – groups of immune cells that contain HIV but do not produce new copies. When people stop taking ART, virus in the latent cells begins to multiply, thereby increasing the amount of HIV in a person’s body. The approach being studied in PAUSE represents an important part of a novel multi-component intervention that could eventually enable the immune system to control HIV in the absence of ART for weeks or months.
“In order to ensure that the HIV cure approaches we develop are broadly effective and accessible, it is vital that HIV cure research be conducted among the global population of people living with HIV,” said ACTG Chair Judith Currier, M.D., M.Sc., University of California Los Angeles. “There are key differences between the HIV epidemic in African countries and the United States; for example, there are variations in viral subtypes as well as in the sex and age distribution of HIV and prevalence of co-morbidities. By situating this study in Africa, we hope to gain important insights into how to optimize HIV cure efforts in the part of the world with the greatest HIV burden.”
This multi-center trial will enroll 48 participants between the ages of 18 and 70 who are virally suppressed on ART, with the expectation that at least 40 percent of participants will be cisgender women. Participants will be randomized in a two-to-one ratio to receive either a single intravenous infusion of 3BNC117-LS-J (30 mg/kg) and a single intravenous infusion of 10‑1074-LS-J (10 mg/kg), or a placebo for both. All participants will discontinue ART two days later. Participants will be closely monitored during their treatment interruptions over the course of 24 weeks. If they remain virally suppressed after that, they may remain off treatment for up to 72 weeks total. Participants will restart HIV treatment when they meet the criteria to do so, including CD4 count decline to below 350 copies/μL or increase in viral load to more than 1000 copies/mL for four weeks in a row, among others.
“The two bNABs being evaluated in PAUSE have shown promise in earlier studies and this study gives us the opportunity to understand that they work among African participants,” said Mina Hosseinipour, MD, MPH, University of North Carolina (UNC) project Malawi at Kamuzu Central Hospital Global, and Co-Chair of PAUSE. “This study has the potential to teach us many things, including how well-tolerated they will be, how effective they are at maintaining durable viral suppression in the absence of ART, and whether they will be associated with a decrease in the size of the latent HIV reservoir.”
PAUSE is being conducted in collaboration with the HIV Vaccine Trials Network (HVTN) and the HIV Prevention Trials Network (HPTN). It is open to select ACTG, HVTN, and HPTN clinical research sites in Africa.
“It’s exciting to see past work on broadly neutralizing human monoclonal antibodies to HIV in South Africa being leveraged as this protocol moves forward,” said Larry Corey, M.D., Principal Investigator of HVTN’s Leadership and Operations Center, headquartered at Fred Hutch Cancer Center in Seattle.
PAUSE is sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (which also co-funds ACTG, HVTN, and HPTN with other NIH institutes). The study is co-funded by the Bill & Melinda Gates Foundation (under INV-006731, INV-010579, and INV-008352). The bNAbs were manufactured by Just-Evotec and are being supplied by the Rockefeller University.
“Ensuring that HIV cure strategies work for diverse populations is key to ACTG’s HIV cure research agenda,” said Marina Caskey, MD, the Rockefeller University and Weill Cornell Medicine, and Vice-Chair of PAUSE. “We have engaged with the communities of local investigators and people living with HIV from early on in the development and design of PAUSE to ensure that we understand their priorities, needs, and challenges in order to ultimately develop and implement successful HIV cure strategies.”
PAUSE is led by Dr. Hosseinipour and Rebone Maboa, MBChB, DOHM, The Aurum Institute (Co-Chairs) and Dr. Caskey and William Hahn, MD, PhD, Fred Hutch Cancer Center (Co-Vice Chairs). ACTG is led by Dr. Currier and Joseph J. Eron, M.D., UNC (ACTG Vice-Chair).
For more information about PAUSE, please visit clinicaltrials.gov.
About ACTG
ACTG is the world’s largest and longest running clinical trials network focused on HIV and other infectious diseases and the people living with them. It is funded by NIAID and collaborating NIH Institutes under award numbers UM1 AI068636, UM1 AI107716, and UM1 AI068634. Founded in 1987, ACTG conducts research to improve the management of HIV and its comorbidities; develop a cure for HIV; and innovate treatments for tuberculosis, hepatitis B, and emerging infectious diseases. It comprises thousands of dedicated researchers, staff, and community members who are pursuing research into novel treatments and cures for infectious diseases at 65 locations across four continents, with the ultimate goal of advancing science that meaningfully impacts the lives of the people we serve.