Progressive transformation of the HIV-1 reservoir cell profile over two decades of antiviral therapy

• DOI: 10.1016/j.chom.2022.12.002
• Publication Date: 2023-01-02T15:46:26Z
• Authors: Xiaodong Lian; Kyra W. Seiger; Elizabeth M. Parsons; Ce Gao; Weiwei Sun; Gregory T. Gladkov; Isabelle C. Roseto; Kevin B. Einkauf; Matthew R. Osborn; Joshua M. Chevalier; Chenyang Jiang; Jane Blackmer; Mary Carrington; Eric S. Rosenberg; Michael M. Lederman; Deborah K. McMahon; Ronald J. Bosch; Jeffrey M. Jacobson; Rajesh T. Gandhi; Michael J. Peluso; Tae-Wook Chun; Steven G. Deeks; Xu G. Yu; Mathias Lichterfeld
• Keywords: Viremia

HIV-1 establishes a life-long reservoir of virally infected cells which cannot be eliminated by antiretroviral therapy (ART). Here, we demonstrate markedly altered viral profile long-term ART-treated individuals, characterized large clones intact proviruses preferentially integrated in heterochromatin locations, most prominently centromeric satellite/micro-satellite DNA. Longitudinal evaluations suggested that this specific configuration results from selection processes promote the persistence repressive chromatin positions, while permissive chromosomal locations are more likely to eliminated. A bias toward integration sites was also observed for study participants who maintained control after discontinuation therapy. Together, these raise possibility antiviral mechanisms during ART may induce an structure with features deep latency and, possibly, limited abilities drive rebound viremia upon treatment interruptions.