For all people living
with HIV, antiretroviral therapy (ART) unquestionably represents the best
opportunity to achieve viral suppression, conserve or recover immune function,
and prevent HIV-related diseases. ART should therefore be taken indefinitely.
interruptions may be necessary in certain challenging cases: treating another illness,
unbearable ART side-effects, etc. Also, research that tests promising
strategies like immune-based therapies and aims to achieve HIV eradication or
ART-free control of HIV viral load may require that HIV-positive volunteers
interrupt their ART and be closely monitored: an approach referred to as an ‘analytical
treatment interruption’, or ATI.
In these studies, the
use of ATIs is justified because, so far, no biomarker (a sign detected in the
blood, for example) can predict post-treatment viral control and, consequently,
help assess the efficacy of the tested strategies. Until such a biomarker is
discovered, researchers can only rely on how long the HIV viral load remains
suppressed, from the moment ART is interrupted to the first viral load rebound,
as a study endpoint.
However, viral rebounds
and potential consequences raise concerns and call for caution. Potential
consequences can include the development of a resistant virus, an acute
retroviral syndrome (signs of
HIV infection, reminiscent of the primary stages of the infection),
thrombocytopaenia (low platelet counts), AIDS-defining events and HIV-related
Another issue faced by
the scientific community is that while research employing ATIs is expanding
worldwide, clinical trial designs are so heterogeneous that comparing their
results can be challenging.
A group of HIV experts
gathered in July 2018 in the US to discuss these concerns and reach consensus
on recommendations for the use of ATIs in research. Their recommendations are
mostly based on expert opinion, but are likely to have a significant influence
on future clinical trials.
Separately, in November 2018, community
recommendations on research involving ATIs were published.