I-108 Assessing the contribution of myeloid cells to HIV-1 persistence under ART

Abstract

Assessing whether myeloid cells support HIV-1 persistence in the face of effective ART represents a significant technical challenge. As a result, there is as yet, no direct evidence that myeloid cells play any role in viral persistence in ART-suppressed individuals. As a consequence, research on myeloid cell reservoirs is falling into obscurity. Infection of macrophages can only be initiated by HIV-1 variants that have the ability to use low levels of CD4 on the cell surface. Therefore, if a functional myeloid reservoir contributes to viral persistence under effective ART, we would predict that viremia that rebounds following analytic treatment interruption (ATI), would contain viral variants that have a high affinity for CD4. We have developed an approach that allows identification of low frequency macrophage-tropic variants in rebounding viremia post ATI. Through single genome amplification (SGA), we cloned a large number of viral envelopes from plasma of individuals who underwent ATI. Furthermore, we have assessed whether macrophage-tropic viruses contributed to viral rebound in individuals who exhibited prolonged remission after receiving reduced intensity bone marrow transplant When these envelopes were used to construct recombinant molecular clones, they conferred the ability to fuse with, and replicate within primary macrophages. We believe that these results provide strong evidence for the existence of a myeloid cell reservoir in infected individuals on suppressive ART and furthermore, that this reservoir contributes to viral rebound when ART is interrupted. The longevity and the anatomic source of the reservoir from which these macrophage-tropic viruses originate, is under investigation.