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

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.

MeSH terms

  • Antiparasitic Agents / therapeutic use
  • Chagas Disease* / complications
  • Chagas Disease* / drug therapy
  • Chagas Disease* / parasitology
  • Coinfection* / parasitology
  • Cross-Sectional Studies
  • HIV Infections* / complications
  • HIV Infections* / drug therapy
  • Humans
  • Longitudinal Studies
  • Nitroimidazoles* / therapeutic use
  • Parasitemia / drug therapy
  • Parasitemia / parasitology
  • Polymerase Chain Reaction
  • Prospective Studies
  • Trypanosoma cruzi* / genetics

Substances

  • benzonidazole
  • Nitroimidazoles
  • Antiparasitic Agents

Grants and funding

This work was supported by the Fundação de Amparo à Pesquisa do Estado de São Paulo (12/50273-0 to MASY, 2014/0781-1 - Technical Training scholarship to FDB, 2013/15122-4- Scientific Initiation Scholarship to CMRO), Coordenação de Aperfeicoamento de Pessoal de Nível superior, CAPES - doctoral scholarship to SCVS – 2010 to 2015), National Council for Scientific and Technological Development (CNPq - 314661/2021- 2 - Research Productivity Grant to CB). The funders did not play any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.