Pre-cART inflammation, microbial translocation and Long-Term probability of clinical progressione in people living with HIV

Background. We aimed to investigate the role of pre-cART inammation and microbial translocation (MT) as predictors of clinical progression in HIV+ patients enrolled in the Icona Foundation Study Cohort. Methods. We included Icona patients with plasma stored within 6 months before cART initiation and at least one CD4 count after therapy available. Circulating biomarker: LPS, sCD14, EndoCab, hs-CRP. KaplanMeier curves and Cox regression models were used. We dened the endpoint of clinical progression as the occurrence of a new AIDS-dening condition, severe non-AIDS condition (SNAEs) or death whichever occurred rst. Follow-up accrued from the data of starting cART and was censored at the time of last available clinical visit. Biomarkers were evaluated as both binary (above/below median) and continuous variables (logescale). Results. We studied 486 patients with 125 clinical events:10.8 (0.77-14.8)/1000 PYFU new AIDS, 18.3 (14.2-23.3)/1000 PYFU SNAEs, and 5.56 (3.40-8.57)/1000 PYFU deaths. Among morbidity events, the incidence of infectious-related events was 19.4 (15.2-24.5)/1000 PYFU. Hs-CRP seemed to be the only biomarker retaining some association with the endpoint of clinical progression (i.e. AIDS/SNAEs/death p=.056). Conclusions. Circulating pre-cART hs-CRP but not MT seems associated with the risk of disease progression after cART initiation, suggesting that pre-therapy HIV-driven pro-inammatory milieu might overweight MT and its downstream immune-activation. This result should help guiding the design of interventional studies.