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

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 RNA50 copies/mL), compared with those having lower HIV DNA (67.2% for .10000, 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 24months (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 (P0.02). 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).