Longitudinal Genetic Characterization Reveals That Cell Proliferation Maintains a Persistent HIV Type 1 DNA Pool...

Area of Science:

• Virology
• Immunology
• Genetics

Background:

• The stability of the human immunodeficiency virus type 1 (HIV-1) reservoir and the role of cellular proliferation in its maintenance during antiretroviral therapy (ART) are not fully understood.
• Investigating HIV-1 dynamics in different T-cell subsets and tissue compartments during effective ART is crucial for understanding viral persistence.

Purpose of the Study:

• To conduct a longitudinal analysis of HIV-1 in T-cell subsets across various tissue compartments.
• To determine the stability and genetic characteristics of the HIV-1 reservoir in individuals on long-term effective ART.

Main Methods:

• Longitudinal analysis of HIV-1 in T-cell subsets from peripheral blood, gut-associated lymphoid tissue, and lymph node tissue.
• Single-proviral sequencing of intracellular HIV-1 genomes from 8 subjects with virologic suppression on ART at two time points (7-9 months apart).

Main Results:

• HIV-1 DNA integrant frequencies remained stable over time (<4-fold difference) and were highest in memory T cells.
• Phylogenetic analyses revealed significant clonal expansions of viral sequences in treated subjects, predominantly in effector memory T cells from blood and lymph nodes.
• These expansions were largely established before therapy, indicating maintenance rather than de novo generation.

Conclusions:

• The HIV-1 DNA integrant pool in memory T cells is genetically stable during long-term effective ART.
• Cellular proliferation and the longevity of infected cells, rather than ongoing viral replication, are the primary mechanisms maintaining the HIV-1 reservoir.
• These findings have implications for strategies aimed at HIV-1 eradication.