Table 5.

Considerations for Effective and Ethical Implementation of Analytical Treatment Interruptions (People Living with HIV, Clinician-Researchers, and Policy-Makers/Bioethicists, n = 36), United States (2015–2016)

Considerations shared between clinician-researchers, policy-makers/bioethicists, and patient-participants

• Provision of adequate information to study participants about potential risks during informed consent process

• Intensive and frequent monitoring (e.g., viral load, CD4+ count)

• Need back-up regimen for study participants in case ARV resistance develops during ATIs

• Provision of clear criteria for reinstituting antiretroviral treatment, including predetermined CD4+ and HIV RNA thresholds

Considerations from clinician-researchers

• Continued research to obtain sensitive measures of the HIV reservoir, including tissues

• Development of matrix for when treatment interruptions may be indicated and not indicated (e.g., indicated with early ART, therapeutic vaccinations, or if scientists think they cured someone, and not indicated with latency-reversing agents, TLR agonist studies, and pediatric studies as they face prospect of lifelong ARV)

• HIV reservoir reduction of 2 logs or less will not delay time to viral rebound by much; need at least 3–4 logs worth reduction for at least 1 year of ART-free remission

• Development of clear criteria for viral rebound endpoint versus viral set point endpoint are needed

• Accounting for patient-to-patient variability and stochastic nature of viral rebound

• Risk reduction related to monitoring analytical treatment interruption

• Determination of whether control arms should undergo treatment interruptions

• Considerations for how ATIs would be implemented in the real world as opposed to experimental setting as this would require frequent HIV testing (functional cure is more likely than sterilizing cure)

Considerations from policy-makers/bioethicists

• Determination of which participants to enroll in treatment interruption studies, including appropriate CD4+ threshold before ATIs

• Use of minimum duration of ART to test hypothesis

• Counseling of study participants on risk of HIV transmission during treatment interruptions

• Additional research to establish relationship between reservoir assays and time to viral rebound determinations

Considerations from patient-participants

• Adequate support to study participants enrolled in treatment interruption protocols

• Minimize burdens related to frequent monitoring visits (e.g., convenient parking at research sites)

TLR, toll-like receptor.