Pioneering HIV Clinical Trial Begins in Africa: A Ray of Hope

Introduction to the PAUSE Study

The ACTG, an international network dedicated to clinical trials for HIV and other infectious diseases, announced the launch of the PAUSE study. This marks the first HIV cure trial by ACTG on the African continent. The PAUSE study, officially known as A5416/HVTN 806/HPTN 108, is a Phase 1 clinical trial that aims to evaluate the safety and effectiveness of two long-acting broadly neutralizing antibodies (bNAbs)—3BNC117-LS-J and 10-1074-LS-J—compared to a placebo. This study will focus on adults living with HIV who pause their antiretroviral therapy (ART) under structured observation.

The Challenge of HIV

Although current ART manages HIV effectively, it does not cure the disease. ART must be taken for life to keep the virus in check and maintain the immune system. Latent HIV reservoirs—clusters of immune cells harboring inactive HIV—can start producing the virus if ART is stopped, increasing the viral load in the body. The PAUSE study represents a new approach to potentially enable the immune system to control HIV without the need for continuous ART.

Why Africa?

According to ACTG Chair Dr. Judith Currier from the University of California Los Angeles, conducting HIV cure research globally ensures the development of universally effective treatments. Africa, with its unique HIV epidemic characterized by different viral subtypes and diverse demographics, offers valuable insights that can optimize HIV cure efforts. This endeavor aims to adapt treatments to the specific needs of regions burdened with the highest rates of HIV.

Structure of the PAUSE Study

The multi-center trial will enroll 48 participants aged 18 to 70 who are virally suppressed on ART. Participants will be randomly assigned in a 2:1 ratio to receive either the bNAbs or a placebo. Two days after the infusion, they will cease ART under close monitoring for 24 weeks. If they remain virally suppressed, the treatment pause could extend to 72 weeks. Participants will resume ART if their CD4 count drops below 350 copies/µL or if their viral load rises above 1000 copies/mL for four consecutive weeks.

Potential Benefits and Insights

Previous studies have shown the promise of the two bNAbs being tested. Co-Chair Dr. Mina Hosseinipour from the University of North Carolina emphasized the study's potential to provide crucial data on the antibodies' tolerance, effectiveness in maintaining viral suppression without ART, and their impact on latent HIV reservoirs among African participants.

Collaborations and Sponsors

The PAUSE study is conducted in collaboration with the HIV Vaccine Trials Network (HVTN) and the HIV Prevention Trials Network (HPTN), opening at selected ACTG, HVTN, and HPTN sites in Africa. The study, sponsored by the National Institute of Allergy and Infectious Diseases (NIAID) and co-funded by the Bill & Melinda Gates Foundation, represents a significant collaborative effort to advance HIV cure research.

Community Engagement

Marina Caskey, MD, Vice-Chair of PAUSE, underscores the importance of engaging communities from the study's inception to address local priorities and challenges. This engagement ensures the development of effective and accessible HIV cure strategies tailored to diverse populations.

Leadership and Execution

The PAUSE team is led by Dr. Hosseinipour and Rebone Maboa, with co-vice chairs Dr. Caskey and William Hahn from the Fred Hutch Cancer Center. ACTG's leadership, including Dr. Currier and Dr. Joseph J. Eron from UNC, drive the initiative to improve the management and cure of HIV.

About ACTG

Founded in 1987, ACTG is the largest and longest-running network focused on HIV and other infectious diseases. With over 65 locations across four continents, the organization aims to advance scientific research that significantly impacts those living with HIV and other infectious conditions. Funded by NIAID and other NIH Institutes, ACTG is dedicated to developing novel treatments and cures.

Conclusion

The PAUSE study is a significant step forward in HIV research, promising new insights and potential breakthroughs in finding a cure. By focusing on African populations, this study aims to ensure that future HIV treatments are both effective and universally accessible.