Grant: Project Grant

Antiretroviral therapy halts HIV replication and reduces virus levels in blood to below clinical detection limits, thereby reducing HIV-related morbidity, mortality and transmission. But, these therapies are not curative because HIV persists within infected cells called "cellular reservoirs" that can reactivate at any time to produce HIV. While receiving therapy, some people living with HIV experience a perplexing phenomenon called "persistent low-level viremia" (PLLV), where virus levels in blood suddenly rise into the low-detectable range despite previous suppression. Current HIV treatment guidelines presume that PLLV is caused by adherence problems and/or the emergence of HIV drug resistance, and universally recommend that the drug regimen be changed. Nevertheless, medication changes often fail to resolve the viremia, indicating that PLLV can have other causes. It was only recently that studies confirmed what has long been suspected: namely that, during therapy, cellular HIV reservoirs can divide to make many copies of themselves, which can reactivate to produce enough HIV to be detected clinically. The finding that PLLV can originate from the reservoir - and that in some cases, the viremia is not even infectious - ranks among the most important recent discoveries in HIV, one that merits in-depth scientific follow-up and timely translation into clinical practice (as treatment modification will not only be ineffective, but possibly harmful, in such cases). Our multidisciplinary project leverages a unique registry of all people living with HIV in British Columbia who have ever accessed treatment, linked to a large sample repository, to address remaining biomedical and clinical knowledge gaps in our understanding of PLLV, with the ultimate goal of updating clinical guidance on how PLLV should be investigated and managed clinically. Our findings will advance HIV reservoir research and improve clinical care of people living with HIV in BC and internationally.