Determinants of medium and high VACS index in HIV‐positive patients on effective HAART

Non‐AIDS events are the leading cause of death in HIV‐positive patients (pts) on effective HAART. The VACS index, composed by HIV‐RNA, CD4+, age, hemoglobin, FIB‐4, eGFR and HCV co‐infection, has been validated as 5‐year mortality index in HIV‐ positive pts [1]. The aim of our study was to evaluate the prevalence and any possible predictive factors of medium‐high VACS index in a cohort of HIV‐positive pts; we also evaluated whether it relates with markers of systemic immune activation. 501 consecutive HIV‐positive asymptomatic pts on effective HAART (HIV‐RNA <40 cp/ml) were enrolled. T‐cell activation (CD38+, CD8+45R0, CD8+38R0) and differentiation (CD127+) was assessed by flow cytometry; VACS index was calculated closest to the sample timepoint. Comparisons were assessed by Chi‐square test. Factors associated with VACS index equal or greater than 10% (gender, time on HAART, CD4+nadir, AIDS diagnosis, previous or current IDU, immune‐activation markers) in univariate model entered the multivariate logistic regression. Of the 501 patients enrolled, 350 (70%) had a low VACS index (VACS <10%), 143 (28%) a medium index (VACS 10–30%) and 8 (1%) an high one (VACS >30%). Groups (pts with low and medium‐high VACS index) were comparable for CD4+ nadir, AIDS diagnosis, CD8+45RO%, CD8+38RO%, CD127+%. Females, active or previous IDU, pts with shorter HAART exposure showed more frequently medium‐high VACS index (table 1). In the multivariable model, female sex (AOR 6.26, 95% CI 3.45‐11.38, p<0.000), IDU history (AOR 2.409, 95% CI 1.31–4.422, p=0.0045) and current CD38+/CD8% (each% more: AOR 1.122, 95% CI 1.03‐1.21, p=0.004) were all independent predictors of VACS ≥10%. Our data suggest that a persistently‐activated immune profile despite virologically‐suppressive HAART may contribute to all‐cause mortality risk, possibly through its role in accelerating degenerative disease. Possible determinants of gender differences in VACS index (such as hemoglobin) need to be further studied. Variable associated with medium‐high VACS index in univariate model Pts with low (<10%) VACS index (n=350) Pts with medium‐high (>10%) VACS index (n=151) p Female sex ° 69 (19%) 66 (43%) 0.0001 AIDS° 75 (21%) 50 (33%) 0.38 Nadir CD4+ T cells/mmc* 211 (7–600) 183 (4–489) 0.75 HAART duration, years* 8.1 (1–21) 7.9 (1–20) 0.01 IDU° 74 (21%) 50 (33%) 0.004 CD127/CD4 + %* 35 (0–63) 35 (0–58) 0.81 CD127/CD8 + %* 44 (0–55) 45 (0–46) 0.70 CD8 + 45/RO%* 13 (0–43) 14 (0–61) 0.7 CD8 + 38/RO%* 1,5 (0–27) 1,6 (0–13) 0.85 CD8 + CD38 + %* 3.01 (0–23) 4.09 (0–23) 0.004 Data are presented as mean (range) Data are presented as the number (percentage)