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Determinants of long-term survival in late HIV diagnosed individuals: the PISCIS Cohort study

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BACKGROUND: Half of the people living with HIV (PLWH) in Western Countries are still diagnosed late, having a negative impact in their life expectancy and comorbidities. Neither the best determinants of their long-term mortality nor the potential impact of starting an integrase inhibitors (INSTI)-based antiretroviral treatment (ART) are completely understood.
We assessed the impact of immune recovery and INSTI-based ART in their long-term mortality.
METHODS: From the PISCIS prospective cohort we included all adult treatment-naïve PLWH starting ART in 2005-2020 and surviving the first 2 years. We estimated mortality rates (MR) upon immune recovery 2 years after ART initiation and associated prognostic factors using Poisson regression. We also assessed risk-factors for incomplete immune recovery at 2 years (defined as CD4 counts '¤500cells/µL) in a nested case-control study using logistic regression with propensity score matching.
RESULTS: We included 2719 persons (15566.8 person-years of follow-up); 1441 (53%) were late presenters, decreasing from 78.5% in 2005-2008 to 40.9% in 2015-2020 (p<0.01). Among late presenters, 44% achieved CD4 counts >500 cells/µL at 2 years. Overall, 113 patients (4.2%) died (crude all-cause MR 7.3/1000PY [95%CI:6.0-8.7]). MR were higher in late compared to non-late presenters, except for those achieving CD4 counts >500 cells/µL at 2 years (MRR 1.13 [95%CI:0.56-2.30], independent of nadir CD4 counts (test-interaction p=0.48).
In multivariate analysis, risk factors for death included: CD4 recovery <500cells/µL (<200cells/µL:aMRR 4.45 [95%CI:2.17-9.11]; 200-350cells/µL:aMRR 1.71 [95%CI:0.85-3.44]; >350-500cells/µL:aMRR 2.14, [95%CI:1.09-4.18]); viral load >200 c/ml at 2 years (aMRR 2.04 [95%CI:1.13-3.68]); Charlson comorbidity index '¥4 (aMRR 4.11 [95%CI:1.90-8.86]), heterosexual men (aMRR 1.97 [95%CI:1.12-3.46]) and injection drug use (aMRR 2.60 [95%CI:1.37-4.95]).
Overall, 979 PLWH initiated an INSTI-based regimen, which was associated with a trend towards decreased mortality compared to other regimens (aMRR 0.60 [95%CI:0.34-1.05]) and with favorable immune recovery (CD4 counts >500cells/µL, aOR 0.70 [95%CI:0.54-0.90]).
No significant changes in MR were observed over calendar time.
CONCLUSIONS: ART-associated immune recovery at 2 years was a better predictor of long-term mortality than nadir baseline CD4 counts in late ART initiators. Nearly half experienced a favorable immune recovery with a life expectancy similar to non-late presenters. INSTI-based regimens were associated with higher rates of successful immune recovery and survival.