An ordeal that does not heal: understanding barriers to a cure for HIV-1 infection

Mathias Lichterfeld; Ce Gao; Xu G Yu

doi:10.1016/j.it.2022.06.002

An ordeal that does not heal: understanding barriers to a cure for HIV-1 infection

Trends Immunol. 2022 Aug;43(8):608-616. doi: 10.1016/j.it.2022.06.002.

Authors

Mathias Lichterfeld¹, Ce Gao², Xu G Yu³

Affiliations

¹ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Infectious Disease Division, Brigham and Women's Hospital, Boston, MA 02115, USA. Electronic address: mlichterfeld@partners.org.
² Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Infectious Disease Division, Brigham and Women's Hospital, Boston, MA 02115, USA.
³ Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA; Infectious Disease Division, Brigham and Women's Hospital, Boston, MA 02115, USA. Electronic address: xyu@mgh.harvard.edu.

Abstract

With more than 38 million people living with HIV-1 (PLWH) worldwide, developing a cure for HIV-1 remains a major global health priority. Lifelong persistence of HIV-1 is frequently attributed to a pool of stable, transcriptionally silent HIV-1 proviruses, which are unaffected by currently available antiretroviral therapy (ART) or host immune activity. In this opinion article, we propose a more dynamic interpretation of HIV-1 reservoir cell biology and argue that HIV-1 proviruses frequently display residual viral transcriptional activity, making them vulnerable to longitudinal immune-mediated selection processes. Such mechanisms may, over extended periods of ART, induce an attenuated viral reservoir profile characterized by intact proviruses preferentially integrated into heterochromatin locations. We suggest that intensifying and accelerating naturally occurring selection mechanisms might represent a promising strategy for finding a potential cure for HIV-1 infection.

Keywords: HIV; cure; eradication; immune selection; latency; reservoirs.

Publication types

Review
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

CD4-Positive T-Lymphocytes
HIV Infections* / drug therapy
HIV-1*
Humans
Proviruses
Virus Latency

Abstract

Publication types

MeSH terms

Grants and funding