Multi-arm, multi-stage randomised controlled trials for evaluating therapeutic HIV cure interventions.

Area of Science:

• Immunology
• Clinical Trials
• Virology

Background:

• Evaluating immune-based strategies for HIV remission requires rigorous placebo-controlled trials.
• Antiretroviral therapy interruption carries risks, necessitating innovative trial designs.
• Accelerating the development of HIV cure therapies is a critical public health goal.

Purpose of the Study:

• To explore the implementation of Multi-Arm, Multi-Stage (MAMS) trial designs for HIV cure research.
• To assess the suitability of MAMS designs for the EHVA T01 trial evaluating immune interventions.
• To enhance the efficiency of identifying effective immune-based HIV cure agents.

Main Methods:

• The EHVA T01 trial employs a multicentre, MAMS, double-blind, phase 1 and 2 design.
• Participants with HIV-1 undergo analytical treatment interruption after immune interventions.
• MAMS design allows for early stopping of ineffective arms and adaptation of the trial.

Main Results:

• MAMS designs increase the probability of identifying successful immune-based HIV cure treatments.
• This design minimizes the number of participants receiving ineffective agents during treatment interruption.
• The EHVA T01 trial aims to efficiently evaluate multiple immune interventions.

Conclusions:

• MAMS designs are a promising strategy for evaluating complex immune-based HIV cure approaches.
• This adaptive trial methodology is particularly relevant for pipelines with multiple candidate agents.
• Implementing MAMS designs in trials like EHVA T01 can expedite the path to an HIV cure.