HIV-DNA content in different CD4+ T-cell subsets correlates with CD4+ cell : CD8+ cell ratio or length of efficient treatment.

Lara Gibellini,Cristina Mussini,Giovanni Guaraldi,Andrea Cossarizza,Elena Bianchini,Gianluca Carnevale,Vanni Borghi,Simone Pecorini,Margherita Digaetano,Sara De Biasi,Marcello Pinti,Milena Nasi

doi:10.1097/qad.0000000000001510

Abstract

HIV establishes a latent infection at different degrees within naïve (TN) or central (TCM) and effector memory (TEM) CD4 T cell. Studying patients in whom HIV production was suppressed by combined antiretroviral therapy, our main aim was to find which factors are related or can influence intracellular viral reservoir in different CD4 T-cell subsets. We enrolled 32 HIV patients successfully treated for more than 2 years, with a CD4 T-cell count more than 500 cells/μl and plasma viremia undetectable from at least 1 year. Proviral HIV-DNA, the amount of cells expressing signal-joint T-cell receptor rearrangement excision circles and telomere length were quantified by droplet digital PCR in highly purified, sorted CD4 T-cell subsets; plasma IL-7 and IL-15 were measured by ELISA. HIV-DNA was significantly lower in TN cells compared with TCM or to TEM. Conversely, TN cells contained more signal-joint T-cell receptor rearrangement excision circles compared with TCM or to TEM; no appreciable changes were observed in telomere length. HIV-DNA content was significantly higher in TN and TCM cells, but not in TEM, from patients with shorter time of treatment, or in those with lower CD4 : CD8 ratio. Length of treatment or recovery of CD4 : CD8 ratio significantly influences viral reservoir in both TN and TCM. Measuring HIV-DNA in purified lymphocyte populations allows a better monitoring of HIV reservoir and could be useful for designing future eradication strategies.

Highlights

Combined antiretroviral therapy has dramatically reduced morbidity and mortality associated with HIV infection allowing the restoration of the CD4þ T-cell compartment and the suppression of viral production [1]
TN cells contained more signal-joint T-cell receptor rearrangement excision circles compared with TCM or to TEM; no appreciable changes were observed in telomere length
HIV-DNA content was significantly higher in TN and TCM cells, but not in TEM, from patients with shorter time of treatment, or in those with lower CD4R : CD8R ratio

Summary

Introduction

Combined antiretroviral therapy (cART) has dramatically reduced morbidity and mortality associated with HIV infection allowing the restoration of the CD4þ T-cell compartment and the suppression of viral production [1]. The pool of CD4þ T cells includes several subsets with distinct homeostatic requirements, in which HIV can establish latent infection at different degrees. Few studies have quantified HIV-DNA in different CD4þ T-cell subsets from patients with successfully suppressed viraemia. Such studies were performed on a low number of patients and report controversial data, probably due to the high interindividual variability [13]. We aimed at adding additional information to this aspect

Objectives

Methods

Results