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Pausing Antiretroviral Treatment Under Structured Evaluation (PAUSE)

Projects

A Phase I, Randomized, Placebo-Controlled Trial to Evaluate the Safety, Antiviral, and Immunomodulatory Effects of Combining Broadly Neutralizing Antibodies 3BNC117-LS-J and 10-1074-LS-J in ART-Treated Adults with HIV in sub-Saharan Africa, during a Monitored Analytical Treatment Interruption Period.

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-Anne Mathew (Principal Investigator)
  • Prof Sinead Delany-Moretlwe (Sub Investigators)
  • Dr Elizabeth Roos (Sub Investigators)
  • Dr Monique Da Fonseca (Sub Investigators)
  • Dr Juliet Vimbai Rundogo (Sub Investigators)

Latest Update

April 2024

For more details about the PAUSE Study please email rhicomms@wrhi.ac.za

Click here for further details regarding the PAUSE study.

Research and Policy Briefs

PAUSE Study

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