No evidence for ongoing replication on ART in SIV-infected macaques

Area of Science:

• Virology
• Immunology
• Primate Models

Background:

• Assessing human immunodeficiency virus type 1 (HIV-1) replication under optimal antiretroviral therapy (ART) is difficult.
• Existing clinical samples limit the sensitivity for detecting viral evolution during ART.
• Nonhuman primate (NHP) models offer better control over pre-ART evolution and enable more comprehensive analyses.

Purpose of the Study:

• To develop a highly sensitive method for detecting viral evolution during ART.
• To evaluate ongoing viral replication in a controlled NHP model under long-term ART.
• To validate the NHP model's relevance for HIV-1 cure studies.

Main Methods:

• Infection of 21 rhesus macaques (RMs) with barcoded simian immunodeficiency virus (SIVmac239M).
• Early initiation of ART to minimize baseline genetic diversity, with treatment duration ranging from 285 to 1200 days.
• Molecular evolution analyses of near-full-length (nFL) SIV DNA and RNA sequences from various tissues and plasma.
• Treatment interruption in four animals to assess rebound viremia.

Main Results:

• No significant changes in SIV DNA populations were detected in PBMCs, lymph nodes, and spleen during ART.
• Near-full-length SIV RNA sequences from rebound plasma viremia after ART cessation showed no evidence of evolution.
• The study demonstrated a lack of appreciable ongoing replication on effective ART.

Conclusions:

• Effective ART significantly suppresses HIV-1 replication and evolution.
• The NHP model provides a robust platform for studying HIV-1 persistence and potential cure strategies.
• Findings support the emerging consensus on the limited viral replication during effective ART.