James McMahon

The session on HIV remission and control trials focuses on a range of studies from macaque models, to clinical trials and then social research around participants and their HIV negative partners. All abstracts included analytical treatment interruption (ATI) as a component of their presentation.

Nir Eyal provided a comprehensive review of the risks to sexual partners of participants in ATI trials and strategies to minimise transmission risk to these individuals. Then data on PET/CT imaging in the macaque model using radiolabelled anti-HIV antibodies to identify tissue reservoirs and sites of viral rebound in ATI. Impact of CD8 depletion on HIV distribution were demonstrated including revealing HIV in the brain. Thailand ATI trials from early ART-treated participants showed no/minor delay in viral rebound after different interventions: VRC01, HCQ/Vorinostat/Maraviroc, Fiebig 1 individuals and Ad26/MVA vaccine. Data on participant experiences and those declining enrolment in the Thai trials was presented. Clear understanding of ATI risks and a strong altruistic drive was reported. Jacque Wambui provided a fascinating analogy for community engagement using the example of changes in Dolutegravir recommendations for women planning pregnancy. The message? engage community early and continuously around design and conduct of ATI trials.

The common thread in this session was analytical treatment interruption (ATI): markers to predict viral rebound, review of interventions from early treated subjects in these trials and imaging modalities to identify sites of viral rebound in macaque models. Then a series of talks highlighting issues for sexual partners of ATI trial participants, social research describing experiences of ATI from participants and then the importance of community engagement in the design and conduct of these trials

Angela Wahl

The following key topics on analytical treatment interruption (ATI) in HIV remission and control trials were covered: 1) ethical aspects and the community perspective, 2) participant experiences with ATI in remission trials, 3) translating the results of non-human primate ATI studies to human clinical trials, and 4) correlates of rebound.

Nir Eyal highlighted the risks to seronegative partners of ATI trial participants and recommended ways to reduce risk. Carlo Sacdalan showed that in four Thailand ATI trials, pre-ART viral load and the CRF01_AE subtype were associated with time to viral rebound. Holly Peay revealed that in interviews of those who joined or declined participation in the Thailand ATI trials, being off ART was seen as a benefit to both groups, joiners displayed trust in the study team and a sense of altruism, and decliners considered the trials too risky. Jacque Wambui provided community concerns for ATI trials: giving and receiving informed consent, participant understandings of “remission”, “cure” and that ATI trials may not have immediate benefit, and trial justification. Francois Villinger used an immuno-PET/CT in non-human primates to show that the gut and lymph nodes were early sites of viral rebound. Tissue viral rebound preceded viremia by 7-14 days.

It is important to involve the community in ATI trial design from the beginning to ensure participant understanding of trial objectives, risks to participants and their partners, and benefits. ATI trials can consider how to reduce risk to participants’ seronegative partners through recruitment, trial operations, protective care for partners, and measures to reduce harm from any infection. Although ATI trials thus far have resulted in rebound, these studies will inform the efficacy/safety of interventions and future trial design. Tissues serving as early sources of viral rebound in animal ATI studies should be considered as important targets in HIV cure approaches.