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Pre-ART HIV-1 DNA in CD4+ T cells correlates with baseline viro-immunological status and outcome in patients under first-line ART

Ceccherini-Silberstein, F; Cozzi Lepri, A; Alteri, C; Merlini, E; Surdo, M; Marchetti, G; Capobianchi, MR; ... ICONA Foundation Study Group, ; + view all (2018) Pre-ART HIV-1 DNA in CD4+ T cells correlates with baseline viro-immunological status and outcome in patients under first-line ART. Journal of Antimicrobial Chemotherapy 10.1093/jac/dky350. Green open access

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Abstract

OBJECTIVES: We evaluated the association between pre-ART HIV DNA and HIV-infected participant characteristics at baseline as well as with their response to first-line ART. METHODS: Four hundred and thirty-three patients from the ICONA cohort, starting first-line ART after the year 2000, were analysed. Pre-ART HIV DNA was quantified with the modified COBAS TaqMan HIV-1 Test and normalized by CD4+ T cells. Linear correlation between pre-ART HIV DNA and other continuous markers (HIV RNA, CD4 count, markers of inflammation and coagulation) at baseline was evaluated by means of Pearson correlation coefficient and a linear regression model. Survival analyses and Cox regression models were used to study the association between pre-ART HIV DNA and time to viro-immunoclinical events. RESULTS: Pre-ART HIV DNA [median (IQR): 10 702 (3397-36 632) copies/106 CD4+ T cells] was correlated with pre-ART HIV RNA [R2 = +0.44, (P < 0.0001)], CD4+ T cells [R2 = -0.58, (P < 0.0001)] and CD4/CD8 ratio [R2 = -0.48, (P < 0.0001)], while weaker correlations were observed with CD8+ T cells (R2 = -0.20, P = 0.01), IL-6 (R2 = +0.16, P = 0.002) and soluble CD14 (R2 = +0.09, P = 0.05). Patients with higher pre-ART HIV DNA showed lower rate and delayed virological response (defined as HIV RNA ≤50 copies/mL), compared with those having lower HIV DNA (67.2% for >10 000, 81.1% for 1000-10 000 and 86.4% for 10-1000 copies/106 CD4+ T cells; P = 0.0004). Higher pre-ART HIV DNA was also correlated with increased risk of virological rebound (defined as HIV RNA >50 copies/mL) by 24 months (17.2% for >10 000, 7.4% for 1000-10 000 and 4.3% for 10-1000 copies/106 CD4+ T cells; P = 0.0048). Adjusted HRs of all virological rebound definitions confirmed these findings (P ≤ 0.02). CONCLUSIONS: Pre-ART HIV DNA, along with HIV RNA and CD4+ T cell count, should be considered as a new staging marker to better identify people at lower (or higher) risk of viral rebound following achievement of virological suppression (≤50 copies/mL).

Type: Article
Title: Pre-ART HIV-1 DNA in CD4+ T cells correlates with baseline viro-immunological status and outcome in patients under first-line ART
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/jac/dky350
Publisher version: http://dx.doi.org/10.1093/jac/dky350
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: hiv-1 t-lymphocyte virology blood hiv rna hiv dna
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute for Global Health > Infection and Population Health
URI: https://discovery.ucl.ac.uk/id/eprint/10058042
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