Programa de Pós-Graduação em Pesquisa Clínica em Doenças Infecciosas, Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
Laboratório de Pesquisa Clínica em Micobacterioses (LAPCLIN-TB), Instituto Nacional de Infectologia Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil.
PLoS One. 2019 Jun 6;14(6):e0217014. doi: 10.1371/journal.pone.0217014. eCollection 2019.
The implementation of antiretroviral (ARV) therapy caused a significant decrease in HIV-associated mortality worldwide. Nevertheless, mortality is still high among people living with HIV/AIDS and tuberculosis (TB). ARV-naïve HIV patients coinfected with tuberculosis (TB) have more options to treat both diseases concomitantly. Nevertheless, some TB-HIV patients undertaking ARVs (ARV-experienced) are already failing the first line efavirenz-based regimen and seem to display different response to second line ARV therapy and exhibit other predictors of mortality.
We performed a retrospective cohort study including 273 patients diagnosed with TB-HIV and treated at a referral center in Rio de Janeiro, Brazil, between 2008 and 2016. Multivariate analysis and Cox regression models were used to evaluate the effectiveness of ARV therapy regimens (viral load [VL] <80 copies from the 4th to 10th months after TB therapy introduction) and to identify predictors of early mortality (100 days after TB therapy initiation) considering ARV-naïve and ARV-experienced patients adjusting for sociodemographic, clinical and therapeutic covariates.
Survival analysis included 273 patients, out of whom 154 (56.4%) were ARV-naïve and 119 (43.6%) were ARV-experienced. Seven deaths occurred within 6 months of anti-TB treatment, 4 in ARV-naïve and 3 in ARV-experienced patients. Multivariate analysis revealed that in ARV-naïve patients, the chance of death was substantially higher in patients who developed immune reconstitution inflammatory syndrome during the study follow up (HR = 40.6, p<0.01). For ARV-experienced patients, similar analyses failed to identify factors significantly associated with mortality. Variables independently associated with treatment failure for the ARV-naïve group were previous TB (adjusted OR [aOR] = 6.1 p = 0.03) and alcohol abuse (aOR = 3.7 p = 0.01). For ARV-experienced patients, a ritonavir boosted. Protease Inhibitor-based regimen resulted in a 2.6 times higher risk of treatment failure compared to the use of efavirenz based ARV regimens (p = 0.03) and High baseline HIV VL (p = 0.03) were predictors of treatment failure.
Risk factors for mortality and ARV failure were different for ARV-naïve and ARV-experienced patients. The latter patient group should be targeted for trials with less toxic and rifampicin-compatible drugs to improve TB-HIV treatment outcomes and prevent death.
抗逆转录病毒（ARV）疗法的实施使全球与艾滋病毒相关的死亡率显著下降。然而，艾滋病毒/艾滋病和结核病（TB）患者的死亡率仍然很高。同时接受抗逆转录病毒治疗和结核病治疗的 ARV 初治 HIV 患者有更多的选择。然而，一些正在接受 ARV 治疗的 TB-HIV 患者（ARV 经验丰富）已经对基于依非韦伦的一线方案产生耐药，并且似乎对二线 ARV 治疗有不同的反应，并表现出其他死亡预测因素。
我们进行了一项回顾性队列研究，纳入了 2008 年至 2016 年期间在巴西里约热内卢的一个转诊中心诊断为 TB-HIV 并接受治疗的 273 例患者。使用多变量分析和 Cox 回归模型评估 ARV 治疗方案的疗效（在开始抗结核治疗后的第 4 至 10 个月，病毒载量[VL] <80 拷贝），并确定 ARV 初治和 ARV 经验丰富患者的早期死亡率（在开始抗结核治疗后 100 天）的预测因素，同时考虑到社会人口统计学、临床和治疗协变量。
生存分析包括 273 例患者，其中 154 例（56.4%）为 ARV 初治，119 例（43.6%）为 ARV 经验丰富。在抗结核治疗后 6 个月内有 7 例死亡，4 例发生在 ARV 初治患者中，3 例发生在 ARV 经验丰富患者中。多变量分析显示，在 ARV 初治患者中，在研究随访期间发生免疫重建炎症综合征的患者死亡的几率显著增加（HR = 40.6，p<0.01）。对于 ARV 经验丰富的患者，类似的分析未能确定与死亡率显著相关的因素。与 ARV 初治组治疗失败相关的独立变量包括既往结核病（调整比值比[aOR] = 6.1，p = 0.03）和酒精滥用（aOR = 3.7，p = 0.01）。对于 ARV 经验丰富的患者，与使用依非韦伦为基础的 ARV 方案相比，使用利托那韦增效的蛋白酶抑制剂方案导致治疗失败的风险增加 2.6 倍（p = 0.03），高基线 HIV VL（p = 0.03）是治疗失败的预测因素。
ARV 初治和 ARV 经验丰富患者的死亡率和 ARV 失败的风险因素不同。后者患者群体应作为试验目标，使用毒性较小且与利福平兼容的药物，以改善 TB-HIV 治疗结果并预防死亡。
