Pre-ART HIV-1 DNA in CD4+ T cells correlates with baseline VIRO-immunological status and outcome in patients under first-line ART
- Authors: Ceccherini-Silberstein F.; Cozzi Lepri A.; Alteri C.; Merlini E.; Surdo M.; Marchetti G.; Capobianchi M.R.; De Luca A.; Gianotti N.; Viale P.; Andreoni M.; Antinori A.; Perno C.F.; D'Arminio Monforte A.; Castagna A.; Castelli F.; Cauda R.; Di Perri G.; Galli M.; Iardino R.; Ippolito G.; Lazzarin A.; Marchetti G.C.; Rezza G.; Von Schloesser F.; Cozzi-Lepri A.; Girardi E.; Lo Caputo S.; Mussini C.; Puoti M.; Ammassari A.; Balotta C.; Bandera A.; Bonfanti P.; Bonora S.; Borderi M.; Calcagno A.; Calza L.; Cingolani A.; Cinque P.; Di Biagio A.; Gori A.; Guaraldi G.; Lapadula G.; Lichtner M.; Madeddu G.; Maggiolo F.; Marcotullio S.; Monno L.; Nozza S.; Quiros Roldan E.; Rossotti R.; Rusconi S.; Santoro M.M.; Saracino A.; Zaccarelli M.; Fanti I.; Galli L.; Lorenzini P.; Rodano A.; Shanyinde M.; Tavelli A.; Carletti F.; Carrara S.; Di Caro A.; Graziano S.; Petrone F.; Prota G.; Quartu S.; Truffa S.; Giacometti A.; Costantini A.; Barocci V.; Angarano G.; Santoro C.; Suardi C.; Donati V.; Verucchi G.; Minardi C.; Quirino T.; Abeli C.; Manconi P.E.; Piano P.; Cacopardo B.; Celesia B.; Vecchiet J.; Falasca K.; Sighinolfi L.; Segala D.; Blanc P.; Vichi F.; Cassola G.; Viscoli C.; Alessandrini A.; Bobbio N.; Mazzarello G.; Mastroianni C.; Pozzetto I.; Molteni C.; Chiodera A.; Milini P.; Nunnari G.; Pellicano G.; Rizzardini G.; Moioli M.C.; Piolini R.; Ridolfo A.L.; Salpietro S.; Tincati C.; Puzzolante C.; Chirianni A.; Borgia G.; Esposito V.; Orlando R.; Bonadies G.; Di Martino F.; Gentile I.; Maddaloni L.; Cattelan A.M.; Marinello S.; Cascio A.; Colomba C.; Baldelli F.; Schiaroli E.; Parruti G.; Sozio F.; Magnani G.; Ursitti M.A.; Acinapura R.; Baldin G.; Capozzi M.; Cicalini S.; Cristaudo A.; Fontanelli Sulekova L.; Iaiani G.; Latini A.; Mastrorosa I.; Plazzi M.M.; Savinelli S.; Vergori A.; Vullo V.; Cecchetto M.; Viviani F.; Bagella P.; Rossetti B.; Franco A.; Fontana Del Vecchio R.; Francisci D.; Di Giuli C.; Caramello P.; Orofino G.C.; Sciandra M.; Bassetti M.; Londero A.; Pellizzer G.; Manfrin V.; Starnini G.; Ialungo A.
- Publication year: 2018
- Type: Articolo in rivista
- OA Link: http://hdl.handle.net/10447/363945
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/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).