Pre-cART Inflammation, Microbial Translocation and Long-Term Probability of Clinical Progression in People Living With HIV 

Background: We aimed to investigate the role of pre-cART inflammation 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. Kaplan-Meier curves and Cox regression models were used. We defined the endpoint of clinical progression as the occurrence of a new AIDS-defining condition, severe non-AIDS condition (SNAEs) or death whichever occurred first. 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 (log e scale). 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-inflammatory milieu might overweight MT and its downstream immune-activation. This result should help guiding the design of interventional studies.