PMID- 34869498 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20211207 IS - 2296-858X (Print) IS - 2296-858X (Electronic) IS - 2296-858X (Linking) VI - 8 DP - 2021 TI - The Effect of Early vs. Deferred Antiretroviral Therapy Initiation in HIV-Infected Patients With Cryptococcal Meningitis: A Multicenter Prospective Randomized Controlled Analysis in China. PG - 779181 LID - 10.3389/fmed.2021.779181 [doi] LID - 779181 AB - Background: The optimal timing for initiation of antiretroviral therapy (ART) in HIV-positive patients with cryptococcal meningitis (CM) has not, as yet, been compellingly elucidated, as research data concerning mortality risk and the occurrence of immune reconstitution inflammatory syndrome (IRIS) in this population remains inconsistent and controversial. Method: The present multicenter randomized clinical trial was conducted in China in patients who presented with confirmed HIV/CM, and who were ART-naive. Subjects were randomized and stratified into either an early-ART group (ART initiated 2-5 weeks after initiation of antifungal therapy), or a deferred-ART group (ART initiated 5 weeks after initiation of antifungal therapy). Intention-to-treat, and per-protocol analyses of data for these groups were conducted for this study. Result: The probability of survival was found to not be statistically different between patients who started ART between 2-5 weeks of CM therapy initiation (14/47, 29.8%) vs. those initiating ART until 5 weeks after CM therapy initiation (10/55, 18.2%) (p = 0.144). However, initiating ART within 4 weeks after the diagnosis and antifungal treatment of CM resulted in a higher mortality compared with deferring ART initiation until 6 weeks (p = 0.042). The incidence of IRIS did not differ significantly between the early-ART group and the deferred-ART group (6.4 and 7.3%, respectively; p = 0.872). The percentage of patients with severe (grade 3 or 4) adverse events was high in both treatment arms (55.3% in the early-ART group and 41.8% in the deferred-ART group; p=0.183), and there were significantly more grade 4 adverse events in the early-ART group (20 vs. 13; p = 0.042). Conclusion: Although ART initiation from 2 to 5 weeks after initiation of antifungal therapy was not significantly associated with high cumulative mortality or IRIS event rates in HIV/CM patients compared with ART initiation 5 weeks after initiation of antifungal therapy, we found that initiating ART within 4 weeks after CM antifungal treatment resulted in a higher mortality compared with deferring ART initiation until 6 weeks. In addition, we observed that there were significantly more grade 4 adverse events in the early-ART group. Our results support the deferred initiation of ART in HIV-associated CM. Clinical Trials Registration: www.ClinicalTrials.gov, identifier: ChiCTR1900021195. CI - Copyright (c) 2021 Zhao, Xu, Lu, Liu, Yuan, Nie, Yu, Liu, Yang, Zhou, Liu, Qin, Chen, Harypursat and Chen. FAU - Zhao, Ting AU - Zhao T AD - Division of Infectious Diseases, Chongqing Public Health Medical Center, Chongqing, China. FAU - Xu, Xiao-Lei AU - Xu XL AD - Division of Infectious Diseases, Chongqing Public Health Medical Center, Chongqing, China. FAU - Lu, Yan-Qiu AU - Lu YQ AD - Division of Infectious Diseases, Chongqing Public Health Medical Center, Chongqing, China. FAU - Liu, Min AU - Liu M AD - Division of Infectious Diseases, Chongqing Public Health Medical Center, Chongqing, China. FAU - Yuan, Jing AU - Yuan J AD - Division of Infectious Diseases, Chongqing Public Health Medical Center, Chongqing, China. FAU - Nie, Jing-Min AU - Nie JM AD - Division of Infectious Diseases, Chongqing Public Health Medical Center, Chongqing, China. FAU - Yu, Jian-Hua AU - Yu JH AD - Division of Infectious Diseases, Xixi Hospital of Hangzhou, Zhejiang, China. FAU - Liu, Shui-Qing AU - Liu SQ AD - Division of Infectious Diseases, Guiyang Public Health Clinical Center, Guizhou, China. FAU - Yang, Tong-Tong AU - Yang TT AD - Division of Infectious Diseases, Public Health Clinical Center of Chengdu, Sichuan, China. FAU - Zhou, Guo-Qiang AU - Zhou GQ AD - Division of Infectious Diseases, The First Hospital of Changsha, Hunan, China. FAU - Liu, Jun AU - Liu J AD - Division of Infectious Diseases, Kunming Third People's Hospital, Yunnan, China. FAU - Qin, Ying-Mei AU - Qin YM AD - Division of Infectious Diseases, The Fourth's Hospital of Nanning, Guangxi, China. FAU - Chen, Hui AU - Chen H AD - School of Biomedical Engineering, Capital Medical University, Beijing, China. FAU - Harypursat, Vijay AU - Harypursat V AD - Division of Infectious Diseases, Chongqing Public Health Medical Center, Chongqing, China. FAU - Chen, Yao-Kai AU - Chen YK AD - Division of Infectious Diseases, Chongqing Public Health Medical Center, Chongqing, China. LA - eng PT - Journal Article DEP - 20211119 PL - Switzerland TA - Front Med (Lausanne) JT - Frontiers in medicine JID - 101648047 PMC - PMC8639871 OTO - NOTNLM OT - HIV OT - IRIS OT - antiretroviral therapy OT - cryptococcal meningitis OT - mortality COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor declared a shared affiliation with one of the authors HC at the time of review. EDAT- 2021/12/07 06:00 MHDA- 2021/12/07 06:01 PMCR- 2021/11/19 CRDT- 2021/12/06 09:21 PHST- 2021/09/18 00:00 [received] PHST- 2021/10/21 00:00 [accepted] PHST- 2021/12/06 09:21 [entrez] PHST- 2021/12/07 06:00 [pubmed] PHST- 2021/12/07 06:01 [medline] PHST- 2021/11/19 00:00 [pmc-release] AID - 10.3389/fmed.2021.779181 [doi] PST - epublish SO - Front Med (Lausanne). 2021 Nov 19;8:779181. doi: 10.3389/fmed.2021.779181. eCollection 2021.