PMID- 38486816 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20240316 IS - 2328-8957 (Print) IS - 2328-8957 (Electronic) IS - 2328-8957 (Linking) VI - 11 IP - 3 DP - 2024 Mar TI - Incidence and Predictors of Tuberculosis-associated IRIS in People With HIV Treated for Tuberculosis: Findings From Reflate TB2 Randomized Trial. PG - ofae035 LID - 10.1093/ofid/ofae035 [doi] LID - ofae035 AB - BACKGROUND: After antiretroviral therapy (ART) initiation, people with HIV (PWH) treated for tuberculosis (TB) may develop TB-associated immune reconstitution inflammatory syndrome (TB-IRIS). Integrase inhibitors, by providing a faster HIV-RNA decline than efavirenz, might increase the risk for this complication. We sought to assess incidence and determinants of TB-IRIS in PWH with TB on raltegravir- or efavirenz-based ART. METHODS: We conducted a secondary analysis of the Reflate TB 2 trial, which randomized ART-naive PWH on standard TB treatment, to receive raltegravir- or efavirenz-based ART. The primary objective was to evaluate the incidence of TB-IRIS. Incidence rate ratio comparing TB-IRIS incidence in each arm was calculated. Kaplan-Meier curves were used to compare TB-IRIS-free survival probabilities by ART arm. Cox regression models were fitted to analyze baseline characteristics associated with TB-IRIS. RESULTS: Of 460 trial participants, 453 from Brazil, Cote d'Ivoire, Mozambique, and Vietnam were included in this analysis. Baseline characteristics were median age 35 years (interquartile range [IQR], 29-43), 40% female, 69% pulmonary TB only, median CD4, 102 (IQR, 38-239) cells/mm(3), and median HIV RNA, 5.5 (IQR, 5.0-5.8) log copies/mL. Forty-eight participants developed TB-IRIS (incidence rate, 24.7/100 PY), 19 cases in the raltegravir arm and 29 in the efavirenz arm (incidence rate ratio 0.62, 95% confidence interval .35-1.10). Factors associated with TB-IRIS were: CD4 /=500 000 copies/mL, and extrapulmonary/disseminated TB. CONCLUSIONS: We did not demonstrate that raltegravir-based ART increased the incidence of TB-IRIS compared with efavirenz-based ART. Low CD4 counts, high HIV RNA, and extrapulmonary/disseminated TB at ART initiation were associated with TB-IRIS. CI - (c) The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. FAU - Coelho, Lara E AU - Coelho LE AUID- ORCID: 0000-0001-7154-8151 AD - National Institute of Infectious Diseases Evandro Chagas, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. FAU - Chazallon, Corine AU - Chazallon C AD - National Institute for Health and Medical Research (INSERM) UMR 1219, Research Institute for Sustainable Development (IRD) EMR 271, Bordeaux Population Health Centre, University of Bordeaux, Bordeaux, France. FAU - Laureillard, Didier AU - Laureillard D AD - Department of Infectious and Tropical Diseases, Nimes University Hospital, Nimes, France. AD - Research Unit 1058, Pathogenesis and Control Chronical Infections, INSERM, French Blood Center, University of Montpellier, Montpellier, France. FAU - Escada, Rodrigo AU - Escada R AD - National Institute of Infectious Diseases Evandro Chagas, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. FAU - N'takpe, Jean-Baptiste AU - N'takpe JB AD - National Institute for Health and Medical Research (INSERM) UMR 1219, Research Institute for Sustainable Development (IRD) EMR 271, Bordeaux Population Health Centre, University of Bordeaux, Bordeaux, France. AD - Programme PACCI/ANRS Research Center, Abidjan, Cote-d'Ivoire. FAU - Timana, Isabelle AU - Timana I AD - Instituto Nacional de Saude, Marracuene, Mozambique. FAU - Messou, Eugene AU - Messou E AD - Programme PACCI/ANRS Research Center, Abidjan, Cote-d'Ivoire. AD - Centre de Prise en Charge de Recherche et de Formation, CePReF-Aconda-VS, Abidjan, Cote D'Ivoire. AD - Departement de Dermatologie et d'Infectiologie, UFR des Sciences Medicales, Universite Felix Houphouet Boigny, Abidjan, Cote d'Ivoire. FAU - Eholie, Serge AU - Eholie S AD - Programme PACCI/ANRS Research Center, Abidjan, Cote-d'Ivoire. AD - Departement de Dermatologie et d'Infectiologie, UFR des Sciences Medicales, Universite Felix Houphouet Boigny, Abidjan, Cote d'Ivoire. FAU - Khosa, Celso AU - Khosa C AD - Instituto Nacional de Saude, Marracuene, Mozambique. FAU - Chau, Giang D AU - Chau GD AD - Pham Ngoc Thach Hospital, Ho Chi Minh City, Vietnam. FAU - Cardoso, Sandra Wagner AU - Cardoso SW AD - National Institute of Infectious Diseases Evandro Chagas, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. FAU - Veloso, Valdilea G AU - Veloso VG AD - National Institute of Infectious Diseases Evandro Chagas, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. FAU - Delaugerre, Constance AU - Delaugerre C AUID- ORCID: 0000-0001-6081-7993 AD - Virology department, APHP-Hopital Saint-Louis, Paris, France. AD - INSERM U944, Paris, France. AD - Universite Paris Cite, Paris, France. FAU - Molina, Jean-Michel AU - Molina JM AD - INSERM U944, Paris, France. AD - Universite Paris Cite, Paris, France. AD - Infectious Diseases Department, AP-HP-Hopital Saint-Louis Lariboisiere, Paris, France. FAU - Grinsztejn, Beatriz AU - Grinsztejn B AD - National Institute of Infectious Diseases Evandro Chagas, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil. FAU - Marcy, Olivier AU - Marcy O AUID- ORCID: 0000-0003-3350-112X AD - National Institute for Health and Medical Research (INSERM) UMR 1219, Research Institute for Sustainable Development (IRD) EMR 271, Bordeaux Population Health Centre, University of Bordeaux, Bordeaux, France. FAU - De Castro, Nathalie AU - De Castro N AUID- ORCID: 0000-0001-5315-1097 AD - National Institute for Health and Medical Research (INSERM) UMR 1219, Research Institute for Sustainable Development (IRD) EMR 271, Bordeaux Population Health Centre, University of Bordeaux, Bordeaux, France. AD - Infectious Diseases Department, AP-HP-Hopital Saint-Louis Lariboisiere, Paris, France. LA - eng PT - Clinical Trial DEP - 20240122 PL - United States TA - Open Forum Infect Dis JT - Open forum infectious diseases JID - 101637045 PMC - PMC10939434 OTO - NOTNLM OT - HIV/AIDS OT - IRIS OT - antiretroviral therapy OT - randomized controlled trial OT - tuberculosis COIS- Potential conflicts of interest. J. M. M. has acted as a consultant, participated in advisory boards, has received speaker fees, and has been an investigator for clinical trials for ViiV Healthcare, Gilead Sciences, and Merck. He has also received research grants from Gilead Sciences. C. D. participated in advisory boards for ViiV Healthcare, Gilead Sciences, BMS, and Merck, and has also received research grants from Gilead and MAD. All other authors report no potential conflicts. EDAT- 2024/03/15 06:44 MHDA- 2024/03/15 06:45 PMCR- 2024/01/22 CRDT- 2024/03/15 03:57 PHST- 2023/12/14 00:00 [received] PHST- 2024/01/18 00:00 [accepted] PHST- 2024/03/15 06:45 [medline] PHST- 2024/03/15 06:44 [pubmed] PHST- 2024/03/15 03:57 [entrez] PHST- 2024/01/22 00:00 [pmc-release] AID - ofae035 [pii] AID - 10.1093/ofid/ofae035 [doi] PST - epublish SO - Open Forum Infect Dis. 2024 Jan 22;11(3):ofae035. doi: 10.1093/ofid/ofae035. eCollection 2024 Mar.