Recently published consensus recommendations discuss analytical antiretroviral treatment interruption (ATI), including who can be included and excluded and when to restart antiretroviral therapy (ART).
A group of experts in HIV recently published results of a consensus meeting that discussed analytical antiretroviral treatment interruption (ATI), because so far, no determination has been made about maximizing benefit while minimizing risk.
In these ATI studies, participants taking antiretroviral therapy (ART) stop taking the medicine to test new therapeutics. But If a person with ART-suppressed HIV stops taking medication, viral load will almost invariably rebound to high levels. ATI seeks to achieve sustained viral suppression in the absence of ART when the goal is to measure effects of novel therapeutic interventions on time to viral load rebound or altered viral setpoint.
ATIs are not yet irreplaceable for assessing the efficacy of interventions aimed at inducing HIV suppression in the absence of ART, they said. The discussion was recently published in Lancet HIV.
Trials with ATIs also intend to determine host, virological, and immunological markers that are predictive of sustained viral control off ART. But differences in ATI trial designs hinder the ability to compare efficacy and safety of interventions across trials.
The meeting was held in 2018 and included 41 experts from around the world, who discussed the scientific value, risks, benefits, and methods of ATIs. The recommendations included considerations for inclusion in ATI trials, exclusion, monitoring, and ART restart criteria.
Patients can generally be considered for inclusion if they have stable CD4 counts of 500 cells/mcL or greater. But it is also possible to consider someone with CD4 levels of 350 cells/mcL or more, the experts said. The decision of which threshold to use will depend on overall risk.
Participants should be free of other comorbidities, generally speaking; they should be excluded if they have active coinfection, cancer, or neurological issues; ART resistance; cardiovascular disease; history of AIDS-defining illness and CD4 nadir; pregnancy; and other issues. Patients should also be excluded if they are having unprotected sex or putting other partners at risk.
The stakeholders agreed that ATI studies are justifiable if the risk is understood by the participants.
Regarding monitoring while off ART, most experts agreed that weekly testing is best, at least for 12 weeks, and then possibly moving to every other week. Most individuals rebound in the first 12 weeks off ART, the experts said.
ART should be restarted if requested by the participant or by the provider, if pregnancy occurs, or if ART is needed for reasons not related to HIV, they said.
Julg B, Dee L, Ananworanich J, et al. Recommendations for analytical antiretroviral treatment interruptions in HIV research trials—report of a consensus meeting [published online March 15, 2019]. Lancet HIV. doi: 10.1016/S2352-3018(19)30052-9.