Mentored Scientist Award

Antiretroviral (ARV) therapy has greatly reduced HIV-related mortality, but treated patients still display excess mortality compared to HIV-negative individuals. This mortality is mostly driven by "non-AIDS defining conditions" such as cardiovascular and hepatic disease as well as non-AIDS related malignancies. One theory about the etiology of this excess mortality is that some patients with HIV may have systemic inflammation and/or states of hypercoagulability which persist during effective ARV therapy; these states may be central to the pathogenesis of the excess mortality seen in treated HIV patients. These theories have led many to revisit the question of the optimal timing of ARV initiation ("when to start"). While most now recommend ARV initiation when a patient's CD4+ count is 350 cells/µL, there is mounting evidence suggesting possible long-term benefits of earlier initiation. This, however, has not been clearly demonstrated in randomized trials. Despite the links between levels of inflammatory biomarkers and mortality in some long-term treated patients, little is known about these biomarkers in the early stages of HIV infection. Similarly, little is known about these biomarkers and their evolution during ARV initiation. It therefore remains unknown how early different inflammatory states might be established, and whether early initiation of ARVs might prevent these from becoming chronic. We therefore aim to study the levels of well-validated biomarkers of inflammation and hypercoagulability in three patient groups: 1) patients initiating ARVs early, 2) patients deferring ARV therapy for the first several years of their disease, and 3) HIV-negative patients. The results of this study are expected to provide important information about HIV pathogenesis, inform ARV treatment decisions, and lay the groundwork for more intensive and prospective studies of these critical questions.