Modern combination antiretroviral therapy (cART) can bring HIV-1 in blood plasma to
level undetectable by standard tests, prevent the onset of acquired immune deficiency syndrome
(AIDS), and allow a near-normal life expectancy for HIV-infected individuals. Unfortunately,
cART is not curative, as within a few weeks of treatment cessation, HIV viremia in most patients
rebounds to pre-cART levels. The primary source of this rebound, and the principal barrier to a
cure, is the highly stable reservoir of latent yet replication-competent HIV-1 proviruses integrated
into the genomic DNA of resting memory CD4+ T cells. In this review, prevailing models for how
the latent reservoir is established and maintained, residual viremia and viremic rebound upon withdrawal
of cART, and the types and characteristics of cells harboring latent HIV-1 will be discussed.
Selected technologies currently being used to advance our understanding of HIV latency will also
be presented, as will a perspective on which areas of advancement are most essential for producing
the next generation of HIV-1 therapeutics.
Keywords: HIV, latency, provirus, integration, residual viremia, antiretroviral, T cell, CD4, TCR, clonal expansion, homeostatic
maintenance, multiple displacement amplification, MDA.
open access plus
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