Dynamics in HIV-DNA levels over time in HIV controllers.

Véronique Avettand‐Fenoel,Pauline Lopez,Asier Saez‐Cirion,Olivier Lambotte,Elise Gardiennet,Nicolas Noel,Laurence Meyer,Tatiana Bayan,Camille Lecuroux,Faroudy Boufassa,Pauline Trémeaux,The Codex Anrs Cohort Study Group ,Valérie Monceaux,Christine Rouzioux,Brigitte Autran

doi:10.1002/jia2.25221

Abstract

Introduction HIV controllers (HIC) maintain viraemia at low levels without antiretroviral treatment and have small HIV reservoirs. Nevertheless, they are heterogeneous regarding their risk of infection progression. The study of reservoirs can help elucidate this control. This study aimed to explore the factors implicated in the pathogenesis of HIV infection that are potentially associated with HIV reservoirs and their dynamics in HIC.MethodsIndividuals living with HIV included in the ANRS‐CODEX cohort with at least two HIV‐DNA measurements between 2009 and 2016 were selected. The total HIV‐DNA levels had been quantified prospectively from blood samples. Mixed‐effect linear models estimated the HIV‐DNA dynamics over time.ResultsThe median (interquartile range (IQR)) HIV‐DNA level was 1.5 (1.3 to 1.9) log copies/million peripheral blood mononuclear cells at inclusion (n = 202 individuals). These low levels showed heterogeneity among HIC. Lower levels were then associated with the protective HLA‐B*27/B*57 alleles and/or lower HIV‐RNA level at inclusion, negative hepatitis C virus serology, lower HIV‐suppressive capacity of specific CD8 T cells and lower levels of immune activation and inflammation. Interestingly, mathematical modelling of the dynamics of HIV‐DNA over time (840 measurements) showed that the number of infected cells decreased in 46% of HIC (follow‐up: 47.6 months) and increased in 54% of HIC. A multivariate analysis indicated that HLA‐B*27/B*57 alleles, a low level of HIV‐RNA and a low level of HIV‐DNA at inclusion were markers independently associated with this decrease.ConclusionsThese results offer new insights into the mechanisms of long‐term control in HIC. In half of HIC, the decrease in HIV‐DNA level could be linked to tighter viral control and progressive loss of infected cells. These findings allow the identification of HIC with a low risk of progression who may not need treatment.

Highlights

HIV controllers (HIC) maintain viraemia at low levels without antiretroviral treatment and have small HIV reservoirs
This study aimed to explore the factors involved in HIV pathogenesis (HIV-RNA load, activation and inflammation biomarkers, the presence of allele HLA-B*27 and/or -B*57 and specific immune responses) that could be associated with the magnitude and dynamics of blood HIV reservoirs in HIC
The question of the evolution of HIV reservoirs over the course of long-term control, which is characteristic of HIC, may offer new insights into the mechanisms of HIV persistence in HIC

Summary

Introduction

HIV controllers (HIC) maintain viraemia at low levels without antiretroviral treatment and have small HIV reservoirs. Human immunodeficiency virus type 1 (HIV-1) controllers (HIC) are a rare group of individuals living with HIV who maintain HIV viraemia at extremely low or even undetectable levels in the absence of antiretroviral treatment [1] They are a heterogeneous group composed of subsets with different characteristics; some of them experience immunologic and/or virologic progression [2,3], whereas others have an extremely high level of control over infection for years [4]. Several parameters have been associated with this spontaneous viral control (among others, protective human leucocyte antigen (HLA) alleles and effective HIV-specific CD4 and CD8 T-cell responses) [5,6] The impact of those parameters on the control of HIV replication and on the evolution of HIV reservoirs determines the long-term future of these HIC and raises the question of whether some or all of them need antiretroviral treatment. Investigating these reservoirs can help elucidate this long-term control

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