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

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de Freitas, Vera Lucia Teixeira ; Novaes, Christina Terra Gallafrio ; Sartori, Ana Marli Christovam ; Carvalho, Noemia Barbosa ; da Silva, Sheila Cristina Vicente ; Nakanishi, erika Shimoda ; Salvador, Fernando ; de Castro, Cleudson Nery ; Bezerra, Rita Cristina ; Westphalen, Elizabeth Visone Nunes ; de Oliveira, Caroline Medeji Ramos ; Busser, Felipe Delatorre ; Ho, Yeh-Li ; Buccheri, Renata ; Bonilla, Carolina ; Shikanai-Yasuda, Maria Aparecida
Número total de Autores: 16
Tipo de documento: Artigo Científico
Fonte: PLoS Neglected Tropical Diseases; v. 18, n. 2, p. 24-pg., 2024-02-01.
Resumo

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 similar to 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/mu L, 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. (AU)

Processo FAPESP: 13/15122-4 - Monitoramento de pacientes imunodeprimidos com doença de Chagas: níveis de parasitemia e associação com o perfil, polimorfismo de citocinas sobrevida e características dos isolados de Trypanosoma cruzi em transplante de órgãos, uso de drogas imunossupress
Beneficiário:Caroline Medeji Ricardo dos Santos
Modalidade de apoio: Bolsas no Brasil - Programa Capacitação - Treinamento Técnico
Processo FAPESP: 12/50273-0 - Monitoramento de pacientes imunodeprimidos com Doenças de Chagas: níveis de parasitemia e associação com o perfil, poliformismo de citonas sobrevidas e características dos isolados Trypanosoma cruzi em transplante de órgãos, uso de drogas imunossupressoras e co-infecção com o vírus da imunodeficiência humana
Beneficiário:Maria Aparecida Shikanai Yasuda
Modalidade de apoio: Auxílio à Pesquisa - Regular