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INITIATION OF ART BASED ON INTEGRASE INHIBITORS INCREASES THE RISK OF IRIS
Marine Dutertre1, Lise Cuzin2, Pascal Puglièse3, Veronique Joly4, Marc-Antoine Valantin5, Laurent Cotte6, Thomas Huleux7, Pierre Delobel2, Guillaume Martin-Blondel1
1Toulouse Univ Hosp, Toulouse, France,2CHU Toulouse, Toulouse, France,3CHU de Nice, Nice, France,4Bichat Hosp, Paris, France,5AP–HP, Paris, France,6Hospices Civils de Lyon, Lyon, France,7Cntr Hosp de Tourcoing, Tourcoing, France
Immunocompromised HIV-infected patients frequently initiate ART based on integrase inhibitors (INSTI). Together with a low CD4 T cell count and a high likelihood of opportunistic infection, the sharp control of viral replication associated with INSTI-based ART might synergize the risk of immune reconstitution inflammatory syndrome (IRIS). Our aim was to determine the incidence of IRIS in exposed patients who initiated ART with or without INSTI as a third agent.
We selected from the Dat'AIDS cohort patients with a CD4 T cell count < 200/mm3 starting from 01/01/2010 to 01/01/2015 ART based on 2 NRTIs associated with a bPI, a NNRTI or an INSTI, and admitted to hospital within 6 months. IRIS events were defined as symptoms consistent with an infectious or inflammatory condition associated with a drop of > 2 log10 copies/mL of HIV viral load, not explained by a newly acquired infection, the expected clinical course of a previous infection, or side-effects. Three physicians blinded to the ART regimen evaluated files and determined the classification by consensus. Characteristics associated with IRIS were analyzed in uni-and multivariate analysis.
The study population included 2287 patients from 15 centers in France. Median age was 45 years (IQ25-75 37-53), and 63% were men. The third agent was bPI in 65%, NNTI in 12%, and INSTI in 12%. At ART initiation, the median HIV viral load and CD4 T cell count were 5.2 log10 copies/mL (4,8-5,7) and 83/mm3 (31-146). IRIS occurred in 41 patients (1.8%) and was associated with tuberculosis (12 cases), atypical mycobacteria (10), JC virus (6), CMV (5), HHV-8 (4), Toxoplasma (2), Cryptococcus (1) and HBV (1). Patients receiving INSTI-based ART did not differ from those without INSTI regarding pre-ART HIV viral load and CD4 T cell count (table). IRIS occurred in 12/398 (3%) patients receiving INSTI-based ART, compared to 29/1889 (1.5%) patients without INSTI (OR 1.99 (1.1-3.5), p=0.04). Repartition of opportunistic infections did not differ according to ART regimen.
Starting ART based on INSTI in exposed patients is associated with a higher risk of IRIS. The homogenous repartition of opportunistic infections among regimen groups argued against a bias of indication linked to mycobacterial infection and co-medication used, although we cannot preclude it formally. While effective control of HIV replication is key, initiation of ART not based on INSTI might be wise in selected patients at high risk of IRIS, deserving further studies.