The Effect of Early vs. Deferred Antiretroviral Therapy Initiation in HIV-Infected Patients With Cryptococcal Meningitis: A Multicenter Prospective Randomized Controlled Analysis in China
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)...
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2021
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oai:doaj.org-article:91bee15315fa48c39d546d447386a28a2021-11-19T05:37:38ZThe Effect of Early vs. Deferred Antiretroviral Therapy Initiation in HIV-Infected Patients With Cryptococcal Meningitis: A Multicenter Prospective Randomized Controlled Analysis in China2296-858X10.3389/fmed.2021.779181https://doaj.org/article/91bee15315fa48c39d546d447386a28a2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmed.2021.779181/fullhttps://doaj.org/toc/2296-858XBackground: 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-naïve. 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.Ting ZhaoXiao-lei XuYan-qiu LuMin LiuJing YuanJing-Min NieJian-Hua YuShui-qing LiuTong-Tong YangGuo-Qiang ZhouJun LiuYing-Mei QinHui ChenVijay HarypursatYao-Kai ChenFrontiers Media S.A.articleHIVIRISantiretroviral therapymortalitycryptococcal meningitisMedicine (General)R5-920ENFrontiers in Medicine, Vol 8 (2021) |
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DOAJ |
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DOAJ |
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EN |
| topic |
HIV IRIS antiretroviral therapy mortality cryptococcal meningitis Medicine (General) R5-920 |
| spellingShingle |
HIV IRIS antiretroviral therapy mortality cryptococcal meningitis Medicine (General) R5-920 Ting Zhao Xiao-lei Xu Yan-qiu Lu Min Liu Jing Yuan Jing-Min Nie Jian-Hua Yu Shui-qing Liu Tong-Tong Yang Guo-Qiang Zhou Jun Liu Ying-Mei Qin Hui Chen Vijay Harypursat Yao-Kai Chen The Effect of Early vs. Deferred Antiretroviral Therapy Initiation in HIV-Infected Patients With Cryptococcal Meningitis: A Multicenter Prospective Randomized Controlled Analysis in China |
| description |
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-naïve. 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. |
| format |
article |
| author |
Ting Zhao Xiao-lei Xu Yan-qiu Lu Min Liu Jing Yuan Jing-Min Nie Jian-Hua Yu Shui-qing Liu Tong-Tong Yang Guo-Qiang Zhou Jun Liu Ying-Mei Qin Hui Chen Vijay Harypursat Yao-Kai Chen |
| author_facet |
Ting Zhao Xiao-lei Xu Yan-qiu Lu Min Liu Jing Yuan Jing-Min Nie Jian-Hua Yu Shui-qing Liu Tong-Tong Yang Guo-Qiang Zhou Jun Liu Ying-Mei Qin Hui Chen Vijay Harypursat Yao-Kai Chen |
| author_sort |
Ting Zhao |
| title |
The Effect of Early vs. Deferred Antiretroviral Therapy Initiation in HIV-Infected Patients With Cryptococcal Meningitis: A Multicenter Prospective Randomized Controlled Analysis in China |
| title_short |
The Effect of Early vs. Deferred Antiretroviral Therapy Initiation in HIV-Infected Patients With Cryptococcal Meningitis: A Multicenter Prospective Randomized Controlled Analysis in China |
| title_full |
The Effect of Early vs. Deferred Antiretroviral Therapy Initiation in HIV-Infected Patients With Cryptococcal Meningitis: A Multicenter Prospective Randomized Controlled Analysis in China |
| title_fullStr |
The Effect of Early vs. Deferred Antiretroviral Therapy Initiation in HIV-Infected Patients With Cryptococcal Meningitis: A Multicenter Prospective Randomized Controlled Analysis in China |
| title_full_unstemmed |
The Effect of Early vs. Deferred Antiretroviral Therapy Initiation in HIV-Infected Patients With Cryptococcal Meningitis: A Multicenter Prospective Randomized Controlled Analysis in China |
| title_sort |
effect of early vs. deferred antiretroviral therapy initiation in hiv-infected patients with cryptococcal meningitis: a multicenter prospective randomized controlled analysis in china |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/91bee15315fa48c39d546d447386a28a |
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