HPTN 108/ PAUSE STUDY

HPTN 108 Study: Pausing Antiretroviral Treatment Under Structured Evaluation (PAUSE Study). The HPTN 108 Study, also known as the PAUSE Study, is a Phase 1, randomized, placebo-controlled trial investigating the safety, efficacy and tolerability of the combination of two long-acting broadly neutralizing antibodies (bNAbs), 3BNC117-LS-J and 10-1074-LS-J, in ART-treated adults living with HIV in sub-Saharan Africa. The study focuses on whether these bNAbs, administered through intravenous infusion, will be safe, well-tolerated, and capable of maintaining durable viral suppression in the absence of antiretroviral therapy (ART) during a monitored analytical treatment interruption (ATI).

Study Objectives

The primary objective of this study is to determine whether the combination of 3BNC117-LS-J and 10-1074-LS-J can effectively maintain viral suppression in people living with HIV while pausing ART, provided the bNAbs remain at therapeutic levels. The study will assess both the safety and efficacy of this innovative treatment strategy, which could represent a significant advancement in HIV management if proven effective.

Rationale

Broadly neutralizing antibodies (bNAbs) have emerged as promising tools in addressing gaps in HIV prevention, treatment, and potential cure. Analytical treatment interruption (ATI) trial designs offer a unique opportunity to simultaneously explore bNAbs’ capabilities across these domains. Early-phase clinical trials targeting various bNAb classes, such as those focusing on the CD4 binding site (e.g., VRC01, 3BNC117) and the V3 loop (e.g., 10-1074, PGT121), have shown encouraging results, highlighting both the promise and challenges in developing bNAbs as preventive and therapeutic agents.

While most bNAb studies have been conducted in the US or Europe, where clade B HIV is predominant, the burden of the pandemic is heaviest in sub-Saharan Africa, where non-clade B viruses prevail. Evaluating promising therapeutic and curative strategies in this region is crucial due to potential clade-specific virologic features and population-specific immunologic characteristics. Although 3BNC117 and 10-1074 have not been clinically tested in non-clade B regions, a combination of these bNAbs maintained viral suppression for a median of 28 weeks in 76% of chronically HIV-positive participants (13 out of 17; 15 with clade B viruses), demonstrating efficacy even without pre-selection for bNAb sensitivity.

ATIs offer a direct assessment of bNAbs’ antiviral potential, serving as in vivo biomarkers not only for therapeutic or curative efficacy but also for prophylactic capabilities. Administering bNAbs during ATI enables the evaluation of safety and efficiency, providing valuable insights into these candidate antibodies.

Investigators

• Dr Carrie Matthew (Principal Investigator)
• Prof Sinead Delany-Moretlwe (Sub Investigator)

Latest Update

August 2024

For more details about HPTN 108 Study please email rhicomms@wrhi.ac.za

Click here for further details regarding the HPTN 108 Study.