Research SummaryAntiretroviral treatment strategies among perinatally-infected children living with HIV-1: understanding drug resistance evolution and early viral suppression
Pediatric HIV is a growing health challenge worldwide, and has often been sidestepped by the broader compelling narrative of HIV in adults. Our research seeks to advance the field of HIV in our youngest afflicted populations, and provides evidence to streamline therapeutic strategies in children. The perinatally infected pediatric HIV model provides analytical leverage as a disease model to better understand the intricacies of HIV disease progression. The unique advantages include the fact that the infection is due to a single homogenous virus transmission event occurring at birth, thus providing a known timing of infection. Additionally, infection during the perinatal period where long-lived CD4+T cell lymphocytes are scarce due to immaturity of the infant’s immune system provides a substantial advantage when therapy is initiated early.
The overall objective of our research is to elucidate specific pathways of immune-protection and viral suppression in perinatally acquired HIV-1 using novel technological approaches including whole genome analysis, next-generation sequencing and mathematical modeling. First, by comparing long-term survivors and normal progressors we will identify specific host genetic markers and viral variants that may be associated with slow disease progression. Second, by characterizing drug resistance in minor viral populations as it emerges in children initiated on antiretroviral therapy, we could potentially streamline therapeutic strategies in children. Specifically, we will examine whether the current dose escalation strategy of nevirapine initiation in children promotes minor populations of drug resistant virus by a trial comparing strategies in treatment in order to understand the safety profile and evolution of drug resistance in relation to the first-line treatment regimen used in children. Finally, will utilize mathematical modeling techniques to decipher viral decay rates in plasma and in the long-lived viral reservoirs in the setting of early ART in infants and younger children, which could offer new insights into effective HIV control. The results of these studies could bring us closer to practical pathways towards successful virus eradication and novel therapeutic strategies for HIV infection in children.