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

Title
Determinants of long-term survival in late HIV diagnosed individuals: the PISCIS Cohort study
Presenter
Raquel Martin-Iguacel
Authors
R. Martin-Iguacel * (1,2), J. Reyes-Urueña (1), J. Casabona (1), A. Bruguera (1), J. Aceiton Cardona (1), Y. Diaz Rodriguez (1), S. Moreno Fornes (1), P. Domingo (3), V. Falcó (4), A. Imaz (5), I.S. Johansen (2), J.M. Miró (6), J.M. Llibre (7), PISCIS study group
Institutions
(1) Centre for Epidemiological Studies on Sexually Transmitted Infections and HIV/AIDS of Catalonia (CEEISCAT), Badalona, Spain, (2) Odense University Hospital, Infectious Diseases, Odense, Denmark, (3) Hospital Sant Pau, Barcelona, Spain, (4) Hospital de Vall d'' Hebron, Barcelona, Spain, (5) Hospital de Bellvitge, Barcelona, Spain, (6) Hospital Clínic-Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain, (7) Infectious Diseases Department and Fight AIDS and Infectious Diseases Foundation, University Hospital Germans Trias i Pujol, Badalona, Spain

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.