Antiretroviral therapies (ART) have significantly extended the life expectancy of people living with HIV and also play a crucial role in preventing HIV transmission. These medications work by inhibiting the replication of HIV within the body. However, despite their effectiveness, ART cannot cure HIV because the virus remains hidden in infected cells known as “cellular reservoirs.” These reservoirs have the potential to reactivate at any time, releasing infectious virus, which is why lifelong ART is necessary.

Under normal circumstances, ART reduces HIV plasma viral loads (the amount of HIV in the blood) to undetectable levels. However, some individuals experience “persistent low-level viremia” during therapy, where viral loads unexpectedly become detectable again. HIV treatment guidelines typically attribute this to issues such as poor drug absorption, inconsistent adherence, or the development of drug resistance, often recommending a change in therapy. Unfortunately, switching therapies doesn’t always resolve the issue, and recent scientific discoveries have shed light on why.

It has been found that sometimes HIV reservoirs undergo clonal expansion, where they divide and produce multiple copies of themselves. When these reservoirs reactivate, they can release enough HIV into the bloodstream to be detected, even if the virus is not infectious. In such cases, changing therapies is ineffective and can lead to unnecessary anxiety and side effects from new medications.

Despite these breakthroughs, there is much we still don’t understand. Who is most at risk for persistent low-level viremia? How long does this phenomenon typically last? What are the clinical implications? Additionally, we lack reliable clinical tests to determine whether viremia stems from cellular reservoirs or other causes, as well as information on how often the virus is infectious in these instances. Most importantly, current clinical guidelines need to be updated to reflect this new knowledge, enabling healthcare providers to make more informed treatment decisions.

In this project, our multidisciplinary team – comprising epidemiologists, basic scientists, clinicians, people living with HIV, and HIV diagnostic experts from across Canada – aims to advance our understanding in this area. Our ultimate goal is to improve care for people living with HIV by providing clearer insights into persistent low-level viremia and updating treatment guidelines accordingly.