6533b7d9fe1ef96bd126c2b5
RESEARCH PRODUCT
Pre-ART HIV-1 DNA in CD4+ T cells correlates with baseline viro-immunological status and outcome in patients under first-line ART
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0301 basic medicineOncologyCD4-Positive T-LymphocytesMaleHIV InfectionsSettore MED/07chemistry.chemical_compoundHIV InfectionPharmacology (medical)ViralProspective StudiesProspective cohort studyAntiinfective agentAdult; Anti-Retroviral Agents; CD4-Positive T-Lymphocytes; DNA Viral; Female; HIV Infections; HIV-1; Humans; Male; Middle Aged; Prospective Studies; Survival Analysis; Treatment Outcome; Viral LoadMiddle AgedViral LoadvirologyHIV CD4Stavudinemedicine.anatomical_structureInfectious DiseasesTreatment Outcomehiv-1 t-lymphocytes virology blood hiv rna hiv dnaAnti-Retroviral AgentsCD4-Positive T-Lymphocyteblood hiv rnaCohorthiv dnaFemaleSurvival AnalysiViral loadARTHumanMicrobiology (medical)Adultmedicine.medical_specialtyAntiretroviral Therapy CD4 Lymphocyte Count StavudineT cellAntiretroviral TherapySettore MED/17 - MALATTIE INFETTIVENO03 medical and health sciencesInternal medicinemedicineHumanst-lymphocytesSurvival analysisPharmacologybusiness.industryProportional hazards modelHIVDNASurvival AnalysisCD4 Lymphocyte CountProspective Studie030104 developmental biologychemistryDNA ViralHIV-1Anti-Retroviral AgentbusinessDNAdescription
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/10 6 CD4+ T cells] was correlated with pre-ART HIV RNA [R 2 = +0.44, (P < 0.0001)], CD4+ T cells [R 2 = '0.58, (P < 0.0001)] and CD4/CD8 ratio [R 2 = '0.48, (P < 0.0001)], while weaker correlations were observed with CD8+ T cells (R 2 = '0.20, P = 0.01), IL-6 (R 2 = +0.16, P = 0.002) and soluble CD14 (R 2 = +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/10 6 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/10 6 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).
year | journal | country | edition | language |
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2018-09-20 |