Early antiretroviral therapy (ART) initiation after cryptococcal meningitis increases mortality, and those unmasking cryptococcosis after <2 weeks of ART have higher mortality. However, it is unknown if those presenting as ART experienced are actually adherent to their ART. Unknowingly, restarting ART in persons, who have discontinued ART, may be a fatal iatrogenic error. To evaluate ART adherence in an exploratory analysis, we collected dried blood spots on 44 HIV-infected persons presenting with cryptococcal meningitis. We quantified tenofovir diphosphate (TFV-DP) and lamivudine (3TC) from dried blood spots. We quantified cumulative ART adherence over the preceding 6–8 weeks based on TFV-DP concentrations and adherence over the last few days based on 3TC concentrations. Of 22 ART experienced, 20 (91%) had quantifiable concentrations. Of 18 receiving tenofovir, 15 (83%) had TFV-DP consistent with drug intake of ≥4 doses/week or moderate adherence. With 3TC, 72% (18/22) had detectable levels consistent with adherence over the last 3 days before measurement. Only three ART-experienced subjects were alive and virally suppressed at 4 months (n = 2 on ART for <30 days; n = 1 with undetectable antiretrovirals). Surprisingly, of 22 who reported not receiving ART, 4 (18%) had quantifiable tenofovir. Most ART-experienced subjects were taking their ART with moderate to good adherence with the majority likely having viral resistance given generally at good ART levels, receipt of intensive adherence counseling, and lack of subsequent viral suppression. The World Health Organization (WHO) guidelines recommend adherence counseling with ART continuation and repeat viral loads in 1–3 months before switching to second-line ART. These recommendations are likely inappropriate in those with central nervous system infections given the additional possible harm of central nervous system immune reconstitution syndrome. Further study to evaluate continuation of ART regimens when presenting with cryptococcosis has benefit, with checking blood levels at presentation potentially being a helpful option. ClinicalTrials.gov Identifier: NCT01802385.

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简短交流：乌干达 HIV 感染者隐球菌性脑膜炎干血斑粘附试验的描述性分析

隐球菌性脑膜炎后早期开始抗逆转录病毒治疗 (ART) 会增加死亡率，而那些在 ART 不到 2 周后发现隐球菌病的人死亡率更高。然而，不知道那些表现出 ART 经历的人是否真的坚持他们的 ART。在不知不觉中，对已停止 ART 的人重新开始 ART 可能是致命的医源性错误。为了在探索性分析中评估 ART 依从性，我们收集了 44 名患有隐球菌性脑膜炎的 HIV 感染者的干血斑。我们从干血斑中量化了替诺福韦二磷酸 (TFV-DP) 和拉米夫定 (3TC)。我们根据 TFV-DP 浓度和过去几天根据 3TC 浓度对过去 6-8 周的累积 ART 依从性进行量化。在 22 名经历过的 ART 中，20 名 (91%) 具有可量化的浓度。在接受替诺福韦治疗的 18 人中，15 人 (83%) 的 TFV-DP 与每周 ≥ 4 剂的药物摄入量或中度依从性一致。对于 3TC，72% (18/22) 的可检测水平与测量前最后 3 天的依从性一致。在 4 个月时，只有 3 名接受过 ART 的受试者存活并受到病毒抑制（n  = 2 接受 ART，持续 <30 天；n = 1，抗逆转录病毒药物检测不到）。令人惊讶的是，在报告未接受抗逆转录病毒治疗的 22 人中，4 人（18%）有可量化的替诺福韦。大多数接受过抗逆转录病毒治疗的受试者接受抗逆转录病毒治疗的依从性为中度至良好，大多数可能具有病毒耐药性，通常在抗逆转录病毒治疗水平良好，接受强化依从性咨询，并且缺乏随后的病毒抑制。世界卫生组织 (WHO) 指南建议在转为二线 ART 之前，在 1-3 个月内继续进行抗逆转录病毒治疗并重复病毒载量的依从性咨询。考虑到中枢神经系统免疫重建综合征的额外可能危害，这些建议可能不适用于中枢神经系统感染患者。进一步研究评估在出现隐球菌病时继续接受 ART 方案有益处，在就诊时检查血液水平可能是一个有用的选择。ClinicalTrials.gov 标识符：NCT01802385。