What is the clinical evidence from this study?

Study design: Other. Population: SIV infection (n=22). Intervention: Post-treatment control (PTC) vs. Non-controllers (NC). Primary outcome: Total SIV-DNA in circulating CD4+ T cells at day 14 post-ATI (copies/10^6 cells) (p=0.010).

What question did this study set out to answer?

This research aims to understand the mechanisms for controlling SIV after the interruption of antiretroviral therapy.

March 2, 2026Open Access

Post-treatment SIV control is associated with specific features of viral persistence before and after treatment interruption

Key Result

Post-treatment SIV controllers maintained significantly lower levels of SIV-DNA in circulating CD4+ T cells compared to non-controllers at day 14 post-treatment interruption.

Key Points

This research aims to understand the mechanisms for controlling SIV after the interruption of antiretroviral therapy.
Conducted longitudinal analysis in cynomolgus macaques infected with SIVmac251
Compared viral markers in controllers versus non-controllers before and after treatment interruption
Analyzed correlations between intact provirus levels and immune responses
Controllers have lower levels of SIV DNA and intact proviruses, both before and after treatment interruption
Fewer intact proviruses correlate with stronger CD8⁺ T-cell suppression and lower viral rebound
Markers of post-treatment control are detectable in lymph nodes prior to and in blood shortly after treatment interruption

Structured PICO

Does early antiretroviral therapy initiation and subsequent interruption affect SIV reservoir size and intact provirus levels in cynomolgus macaques?

Population

SIVmac251-infected male cynomolgus macaques (pVISCONTI study)

Intervention

Antiretroviral therapy (ART) initiated at week 4 or week 24 post-infection, maintained for 2 years, followed by analytical treatment interruption (ATI)

Comparator

Non-controllers (NCs) vs Post-treatment controllers (PTCs), and never-treated macaques

Outcome

Levels of SIV DNA, intact proviruses, transcriptional activity, and viral evolution in blood and tissuessurrogate

In a macaque model of SIV, post-treatment control is associated with a restricted viral reservoir and fewer intact proviruses in lymph nodes before treatment interruption, suggesting immune responses shape the reservoir during treatment.

Main Result

Absolute Event Rate: 13% vs 21%

p-value: p=0.010

Limitations

Limited accessibility of lymph node tissues
NFL amplification could not be achieved for all macaques due to very low reservoir levels in non-lymphoid tissues

Abstract

Mechanisms underlying durable control of HIV after antiretroviral therapy interruption remain poorly understood. Here we provide a comprehensive longitudinal analysis in a non-human primate model of post-treatment control using SIVmac251-infected male cynomolgus macaques (pVISCONTI study). Controllers exhibit lower levels of SIV DNA, intact proviruses, transcriptional activity, and viral evolution compared to non-controllers in blood and tissues long after therapy interruption. Before interruption, controllers already have fewer intact proviruses in lymph nodes, and this difference persists in blood shortly after interruption, prior to viral rebound. Intact provirus levels in lymph nodes before interruption negatively correlate with CD8⁺ T-cell capacity to suppress SIV and reflect rebound magnitude. The study demonstrates that markers of post-treatment control are detectable in lymph nodes before therapy interruption and in blood shortly after, and suggests that host immune responses may shape intact provirus profiles during treatment.

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