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

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).

• Authors: Francesca Ceccherini-Silberstein, Alessandro Cozzi Lepri, Claudia Alteri, Esther Merlini, Matteo Surdo, Giulia Marchetti, Maria Rosaria Capobianchi, Andrea De Luca, Nicola Gianotti, Pierluigi Viale, Massimo Andreoni, Andrea Antinori, Carlo Federico Perno, Antonella d'Arminio Monforte, ICONA Foundation Study Group
• Journal: The Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 73 Issue 12 Pg. 3460-3470 (12 01 2018) ISSN: 1460-2091 [Electronic] England
• PMID: 30247724 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Retroviral Agents
• DNA, Viral

Topics

• Adult
• Anti-Retroviral Agents (therapeutic use)
• CD4-Positive T-Lymphocytes (virology)
• DNA, Viral (analysis, genetics)
• Female
• HIV Infections (drug therapy, virology)
• HIV-1 (genetics, isolation & purification)
• Humans
• Male
• Middle Aged
• Prospective Studies
• Survival Analysis
• Treatment Outcome
• Viral Load