Abstract Body

Background: Immune-reconstitution after therapy (cART) is often either quantitatively or qualitatively incomplete. Aim of the study was to evaluate in the Icona cohort patients (pts) the probability of reaching a CD4/CD8 ratio >=1 after starting cART and its possible protective role against the onset of non-AIDS related events (nADE) or death for any cause. Methodology: Pts were included if started cART, reached undetectable viral load (VL) (<=80 copies/mL) (time 0 of the analysis) and had a CD4/CD8 ratio at undetectability 1. nADE were: cardiovascular events, stroke, non-AIDS defining cancers. Multivariable Poisson regression model was used to analyze factors independently associated with normalization and with clinical progression. Results: 3,236 pts were included, 76.4% males, mean age 39 years, 88.3% Italians, 18.3% CDC stage C. At starting cART, mean CD4 was: 223 cells/uL (range 101-317) and mean CD4/CD8 ratio was 0.39 (range 0.26-0.55). 717 pts (22.2%) were HCV co-infected and 178 (5.5%) HBV. Median CD4 count at time 0 was 378 cells/uL (range 249-518). Over 7,305 PYFU, 458 pts reached a CD4/CD8 ratio >1 [IR=6.3 per 100 PYFU (95%CI 5.7-6.9)]. Probability of normalization was 30%, 95%CI 26%-35% by 15 years using KM method. At multivariable analysis, factors associated with a higher chance of achieving normalization were: a higher CD4/CD8 ratio before starting cART (RR: 1.72 for 0.10 higher, 95%CI 1.62-1.83; p=0.000) and having started cART more recently (RR: 1.03 per more recent year, 95%CI 1.01-1.06; p=0.007). In contrast, older pts (RR: 0.87 per 10 year older, 95%CI 0.78-0.97; p=0.016), homosexual contacts (RR: 0.74 vs. heterosexuals; 95%CI 0.57-0.96; p=0.022), those with a nadir CD4 value below 200 (RR: 0.73 vs. >200, 95%CI: 0.57-0.95; p=0.017), HBV co-infected (RR 0.58 vs. HIV mono-infected, 95%CI: 0.35-0.99; p=0.045) and those treated with AZT/3TC (RR 0.70 95%CI 0.48-1.00 p=0.051) or ddI/d4T (RR 0.31 95%CI 0.11-0.87 p=0.027) using tdf+ftc as reference were less likely to achieve normalization. CD4/CD8 was associated with the risk of developing nADE or death independently of current CD4 count (Table 1). Conclusions: A minority of pts who start cART reaches a CD4/CD8 ratio >1. Younger patients, those with a higher CD4/CD8 ratio at time of viral suppression and those starting cART more recently and with higher CD4 count have higher possibilities to achieve normalization. The CD4/CD8 ratio was predictive of clinical progression independently from CD4 cell count.