# Tools to Quantify and Characterize the Persistent Reservoir in People with HIV-1: Focus on Non-B Subtypes

## TL;DR

This paper reviews tools for measuring HIV-1 reservoirs, emphasizing the need for standardized methods to study non-B subtypes prevalent globally.

## Contribution

The paper highlights the adaptation of existing HIV-1 reservoir quantification tools for non-B subtypes and advocates for global standardization.

## Key findings

- Current tools for measuring HIV-1 reservoirs are mainly developed for subtype B.
- Non-B subtypes dominate global HIV-1 infections but lack standardized reservoir analysis tools.
- Standardized and accessible tools are needed to study subtype-specific reservoir dynamics.

## Abstract

Human immunodeficiency virus type 1 (HIV-1) continues to be a major global health burden. Combination antiretroviral therapy (cART) effectively abrogates HIV-1 replication and has transformed HIV-1 infection from a fatal to chronic disease. While ART can suppress viremia to undetectable levels in people living with HIV-1 (PWH), a small reservoir of cells infected with replication-competent HIV-1 persists and can lead to viral rebound upon ART interruption. This persistent HIV-1 reservoir can be quantified and characterized by measuring replication of infectious HIV-1 using a quantitative viral outgrowth assay (qVOA), or by measuring HIV-1 DNA, RNA, or protein levels as a proxy for the reservoir. Tools to quantify the reservoir in these distinct molecular compartments have been developed for HIV-1 subtype B, which is predominant in the Global North. However, non-B subtypes constitute the majority of HIV-1 infections worldwide. Here, we discuss the wide range of reservoir quantitation and characterization tools, explore their limitations, and, where applicable, their adaptations to non-B subtypes. We conclude that standardized tools should be used to characterize reservoir dynamics of HIV-1 B and non-B subtypes. These tests should be well-validated and accessible to all laboratories world-wide to be able to draw conclusions about subtype-specific reservoir dynamics.