Abstract

BackgroundThe HIV-1 DNA reservoir is an important marker that reflects viro-immunological status and can be affected by multiple viral or cellular factors. Determining the potential factors associated with the size of the HIV-1 DNA reservoir benefits the surveillance of disease progression and antiretroviral treatments.MethodsWe conducted a case control study to explore the factors that may affect the level of HIV-1 DNA. The level of HIV-1 total DNA in peripheral blood at 5 time points was quantified by quantitative PCR. Chronically HIV-1-infected patients whose cell-associated HIV-1 DNA levels were below the detection limit after receiving antiretroviral therapy (ART) for 96 weeks were identified (group 1), and patients who still had detectable levels of cell-associated HIV-1 DNA after ATR treatment were used as the control (group 2).ResultsTwenty-one patients with ultralow levels of cell-associated HIV-1 DNA [<20 copies/106 peripheral blood mononuclear cells (PBMCs)] presented with a lower CD8+ T-cell count (average: 511 ± 191 versus 715 ± 256 cells/μL, p = 0.013) and a higher CD4/CD8 ratio (average: 1.04 ± 0.37 versus 0.72 ± 0.32, respectively, p = 0.002) at week 96. In the multivariate analysis, patients with a higher CD4/CD8 ratio at week 96 were more likely to have levels of HIV-1 DNA below the detection limit (per 0.1 increase, OR = 1.29, 95% CI, 1.05–1.59, p = 0.017).ConclusionAfter matching baseline HIV-1 DNA levels, a higher CD4/CD8 ratio at week 96 was the only factor associated with an ultralow level of HIV-1 DNA. The CD4/CD8 ratio can be used as an easy biomarker to help monitor patients on ART who will be selected to participate in eradication studies.

Highlights

  • The HIV-1 DNA reservoir is an important marker that reflects viro-immunological status and can be affected by multiple viral or cellular factors

  • We focused on analyzing other factors associated with below-detection-level DNA by matching baseline HIV-1 DNA levels between the two groups and found that the CD4/CD8 ratio at week 96 was the only factor associated with an ultralow HIV-1 DNA level

  • Baseline characteristics of the patients In the case control study, the 69 patients with successful treatment were selected from the cohorts and were stratified into two groups according to the level of cellassociated HIV-1 DNA after 96 weeks of antiretroviral therapy (ART)

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Summary

Introduction

The HIV-1 DNA reservoir is an important marker that reflects viro-immunological status and can be affected by multiple viral or cellular factors. Determining the potential factors associated with the size of the HIV-1 DNA reservoir benefits the surveillance of disease progression and antiretroviral treatments. The. The level of peripheral blood mononuclear cell (PBMC)associated HIV-1 DNA can be affected by multiple factors, including the plasma viral load, the peripheral CD4+ Tlymphocyte count, the timing of ART initiation and the duration of ART treatment as well as the immune activation status [11,12,13,14,15,16,17]. Determining the potential viral or cellular factors that are associated with the size of the HIV-1 DNA reservoir benefits the surveillance of disease progression and antiretroviral treatments. In the current case control study, we identified 21 patients with chronic HIV-1 infection who had undetectable cell-associated HIV-1 DNA levels after 2 years of ART treatment. We focused on analyzing other factors associated with below-detection-level DNA by matching baseline HIV-1 DNA levels between the two groups and found that the CD4/CD8 ratio at week 96 was the only factor associated with an ultralow HIV-1 DNA level

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