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定量 PCR 作为一种预测性治疗的标志物及其在 HIV 合并克氏锥虫感染治疗控制中的作用。

Quantitative PCR as a marker for preemptive therapy and its role in therapeutic control in Trypanosoma cruzi/HIV coinfection.

机构信息

Departamento de Molestias Infecciosas e Parasitarias, Faculdade de Medicina, Universidade de Sao Paulo, São Paulo, São Paulo, Brazil.

Laboratorio de Investigacao Medica em Imunologia (LIM 48), Hospital das Clinicas, Faculdade de Medicina, Universidade de Sao Paulo, São Paulo, Brazil.

出版信息

PLoS Negl Trop Dis. 2024 Feb 26;18(2):e0011961. doi: 10.1371/journal.pntd.0011961. eCollection 2024 Feb.

Abstract

BACKGROUND

Trypanosoma cruzi and HIV coinfection can evolve with depression of cellular immunity and increased parasitemia. We applied quantitative PCR (qPCR) as a marker for preemptive antiparasitic treatment to avoid fatal Chagas disease reactivation and analyzed the outcome of treated cases.

METHODOLOGY

This mixed cross-sectional and longitudinal study included 171 Chagas disease patients, 60 coinfected with HIV. Of these 60 patients, ten showed Chagas disease reactivation, confirmed by parasites identified in the blood, cerebrospinal fluid, or tissues, 12 exhibited high parasitemia without reactivation, and 38 had low parasitemia and no reactivation.

RESULTS

We showed, for the first time, the success of the timely introduction of benznidazole in the non-reactivated group with high levels of parasitemia detected by qPCR and the absence of parasites in reactivated cases with at least 58 days of benznidazole. All HIV+ patients with or without reactivation had a 4.0-5.1 higher chance of having parasitemia than HIV seronegative cases. A positive correlation was found between parasites and viral loads. Remarkably, treated T. cruzi/HIV-coinfected patients had 77.3% conversion from positive to negative parasitemia compared to 19.1% of untreated patients. Additionally, untreated patients showed ~13.6 times higher Odds Ratio of having positive parasitemia in the follow-up period compared with treated patients. Treated and untreated patients showed no differences regarding the evolution of Chagas disease. The main factors associated with all-cause mortality were higher parasitemia, lower CD4 counts/μL, higher viral load, and absence of antiretroviral therapy.

CONCLUSION

We recommend qPCR prospective monitoring of T. cruzi parasitemia in HIV+ coinfected patients and point out the value of pre-emptive therapy for those with high parasitemia. In parallel, early antiretroviral therapy introduction is advisable, aiming at viral load control, immune response restoration, and increasing survival. We also suggest an early antiparasitic treatment for all coinfected patients, followed by effectiveness analysis alongside antiretroviral therapy.

摘要

背景

克氏锥虫和 HIV 合并感染可导致细胞免疫抑制和寄生虫血症增加,从而引发进行性恶化。我们应用实时定量 PCR(qPCR)作为预防性抗寄生虫治疗的标志物,以避免致命性恰加斯病再激活,并分析治疗病例的结局。

方法

本研究为混合的横断面和纵向研究,纳入了 171 例恰加斯病患者,其中 60 例合并 HIV 感染。在这 60 例患者中,有 10 例患者出现恰加斯病再激活,通过血液、脑脊液或组织中发现寄生虫而得到证实,12 例患者寄生虫血症较高但未出现再激活,38 例患者寄生虫血症较低且未出现再激活。

结果

我们首次展示了及时引入苯硝唑在高 qPCR 水平检测到高寄生虫血症但未发生再激活的非再激活组中的成功,并且在接受至少 58 天苯硝唑治疗的再激活病例中未发现寄生虫。所有合并或不合并再激活的 HIV 阳性患者的寄生虫血症风险比 HIV 阴性患者高 4.0-5.1 倍。还发现寄生虫与病毒载量呈正相关。值得注意的是,与未治疗的患者相比,治疗的 T. cruzi/HIV 合并感染患者的寄生虫血症从阳性转为阴性的转化率为 77.3%。此外,在随访期间,未治疗的患者发生阳性寄生虫血症的优势比是治疗患者的 13.6 倍。治疗和未治疗的患者在恰加斯病的进展方面没有差异。所有原因死亡率的主要相关因素是更高的寄生虫血症、更低的 CD4 计数/μL、更高的病毒载量和缺乏抗逆转录病毒治疗。

结论

我们建议对 HIV 合并感染患者进行 T. cruzi 寄生虫血症的 qPCR 前瞻性监测,并指出对高寄生虫血症患者进行预防性治疗的价值。同时,建议尽早引入抗逆转录病毒治疗,以控制病毒载量、恢复免疫反应并提高生存率。我们还建议对所有合并感染的患者进行早期抗寄生虫治疗,然后分析与抗逆转录病毒治疗的疗效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/42c5/10896531/e23b4ba2a765/pntd.0011961.g001.jpg

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