HIV evolution and diversity in ART-treated patients

Area of Science:

• Virology
• Immunology
• Genetics

Background:

• Antiretroviral therapy (ART) aims to suppress HIV replication.
• The persistence of HIV genetic diversity during ART is not fully understood.
• Mechanisms maintaining the viral reservoir under ART require further elucidation.

Purpose of the Study:

• To review methods for analyzing intra-patient HIV genetic diversity during ART.
• To discuss the impact of ART on HIV diversity, viral evolution, and drug resistance.
• To explore the role of infected cell proliferation in maintaining the HIV reservoir.

Main Methods:

• Review of existing literature on HIV genetic diversity and evolution.
• Analysis of intra-patient HIV sequence data.
• Examination of viral compartmentalization and drug resistance mechanisms.

Main Results:

• ART affects pre-existing HIV diversity, but viral evolution and replication during therapy remain debated.
• HIV compartmentalization exists across different body tissues.
• Proliferation of latently infected CD4+ T cells before and during ART contributes to the viral reservoir.
• Expanded cell clones with intact proviruses act as a source for residual viremia and potential viral rebound.

Conclusions:

• Proliferation of infected cells, rather than solely ongoing viral replication, is a key mechanism for maintaining the HIV reservoir during ART.
• Identical viral sequences in plasma and cells suggest clonal expansion.
• Understanding HIV diversity and infected cell dynamics may lead to strategies for HIV eradication or control without ART.