Clinical relevance of the plasma load of cytomegalovirus in patients infected with HIV—A survival analysis

Aramă, Victoria; Mihăilescu, Raluca; Rădulescu, Mihaela; Aramă, Sorin Ștefan; Streinu-Cercel, Adrian; Youle, Mike

doi:10.1002/jmv.24027

Cited by 11 publications

(10 citation statements)

References 28 publications

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“…Many authors agree only with the fact that etiotropic therapy causes the reduction of abnormalities on the MRI in patients with cerebral toxoplasmosis within 2 weeks of application [18][19][20].…”

Section: Introductionmentioning

confidence: 99%

“…Brain magnetic resonance imaging (MRI) is the main instrumental method for the diagnosis of cerebral toxoplasmosis but the MRI findings that are present in the literature are contradictory. Many authors agree only with the fact that etiotropic therapy causes the reduction of abnormalities on the MRI in patients with cerebral toxoplasmosis within 2 weeks of application [ 18 – 20 ].…”

Section: Introductionmentioning

confidence: 99%

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Cerebral toxoplasmosis in HIV-infected patients over 2015–2018 (a case study of Russia)

et al. 2020

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Cerebral toxoplasmosis is a leading cause of the central nervous system disorders in acquired immune deficiency syndrome. This study aimed to investigate the clinical course of cerebral toxoplasmosis in human immunodeficiency virus (HIV)-infected individuals. The study included 90 HIV-infected patients with cerebral toxoplasmosis, who underwent inpatient treatment. In case of positive enzyme immunoassay, HIV infection was confirmed with the immunoblot test. The HIV-1 ribonucleic acid level was determined using the polymerase chain reaction method. The flow cytometry was used for counting CD4 (cluster of differentiation 4 cells). Pathomorphological examination included the autopsy, gross and microscopic examination of internal organs, histological and other methods. The incidence of cerebral toxoplasmosis significantly increases at the CD4 count below 100 cells/μl, P < 0.001, and at the HIV viral load above 50 copies/ml, P < 0.05. The clinical picture of cerebral toxoplasmosis included focal symptoms, cognitive impairment, toxic syndrome, mild cerebral symptoms and a meningeal symptom. Given the absence of a specific clinical picture and the absence of abnormal laboratory and instrumental findings, the cerebral toxoplasmosis needs to be diagnosed with a number diagnostic methods combined: clinical examination, laboratory testing, immunological examination, molecular genetic testing and neuroradiological imaging.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cerebral toxoplasmosis in HIV-infected patients over 2015–2018 (a case study of Russia)

et al. 2020

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“…Like other herpesviruses, CMV has a latent phase, during which CMV remains asymptomatic and minimally detectable, and a lytic phase, in which the virus replicates and promotes inflammation (reviewed in reference 6). CMV generally remains asymptomatic in people with healthy immune systems; nevertheless, subclinical replication in blood and at various mucosal sites may contribute to chronic inflammation, especially in PLWH (7)(8)(9). Over time, CMV maintains an outsized proportion of CMV-specific T cells, and CMV replication is itself favored by inflammatory stimuli (4,10,11).…”

mentioning

confidence: 99%

Subclinical Cytomegalovirus DNA Is Associated with CD4 T Cell Activation and Impaired CD8 T Cell CD107a Expression in People Living with HIV despite Early Antiretroviral Therapy

Christensen-Quick

Massanella

Frick

et al. 2019

J Virol

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Most people living with HIV (PLWH) are coinfected with cytomegalovirus (CMV). Subclinical CMV replication is associated with immune dysfunction and with increased HIV DNA in antiretroviral therapy (ART)-naive and -suppressed PLWH. To identify immunological mechanisms by which CMV could favor HIV persistence, we analyzed 181 peripheral blood mononuclear cell (PBMC) samples from 64 PLWH starting ART during early HIV infection with subsequent virologic suppression up to 58 months. In each sample, we measured levels of CMV and Epstein-Barr virus (EBV) DNA by droplet digital PCR (ddPCR). We also measured expression of immunological markers for activation (HLA-DR ϩ CD38 ϩ ), cycling (Ki-67 ϩ ), degranulation (CD107a ϩ ), and the immune checkpoint protein PD-1 on CD4 ϩ and CD8 ϩ T cell memory subsets. Significant differences in percentages of lymphocyte markers by CMV/EBV shedding were identified using generalized linear mixed-effects models. Overall, CMV DNA was detected at 60/181 time points. At the time of ART initiation, the presence of detectable CMV DNA was associated with increased CD4 ϩ T cell activation and CD107a expression and with increased CD8 ϩ T cellular cycling and reduced CD107a expression on CD8 ϩ T cells. While some effects disappeared during ART, greater CD4 ϩ T cell activation and reduced CD107a expression on CD8 ϩ T cells persisted when CMV was present (P Ͻ 0.01). In contrast, EBV was not associated with any immunological differences. Among the covariates, peak HIV RNA and CD4/CD8 ratio had the most significant effect on the immune system. In conclusion, our study identified immune differences in PLWH with detectable CMV starting early ART, which may represent an additional hurdle for HIV cure efforts.IMPORTANCE Chronic viral infections such as with HIV and CMV last a lifetime and can continually antagonize the immune system. Both viruses are associated with higher expression of inflammation markers, and recent evidence suggests that CMV may complicate efforts to deplete HIV reservoirs. Our group and others have shown that CMV shedding is associated with a larger HIV reservoir. Subclinical CMV replication could favor HIV persistence via bystander effects on our immune system. In this study, we collected longitudinal PBMC samples from people starting ART and measured immune changes associated with detectable CMV. We found that when CMV was detectable, CD4 ϩ T cell activation was higher and CD8 ϩ T cell degranulation was lower. Both results may contribute to the slower decay of the size of the reservoir during CMV replication, since activated CD4 ϩ T cells are more vulnerable to HIV infection, while the loss of CD8 ϩ T cell degranulation may impede the proper killing of infected cells.

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“…Consequently, all patients have been treated accordingly (anti-Toxoplasma therapy), showing significant clinical improvement. This not only demonstrated that the early treatment of TE is effective [22,23] but also proved the excellent diagnostic performance and necessity of RT-PCR when detecting TE in BML.…”

Section: Discussionmentioning

confidence: 69%

Diagnostic value of real-time PCR of brain mass lesion in HIV-associated toxoplasmic encephalitis: a case series

et al. 2020

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Background Toxoplasmic encephalitis (TE) is a leading cause of brain mass lesions (BML) in human immunodeficiency viruses (HIV)-infected patients. Yet, so far, no accurate diagnostic approach for TE has been developed. Herein, we presented a case series (9 HIV-infected patients with TG confirmed by RT-PCR of BML) to assess the diagnostic value of reverse transcription-polymerase chain reaction (RT-PCR) on TE. Methods A total of 9 HIV-infected patients with TE confirmed by RT-PCR of BML were included in this study. Clinical data, including clinical symptoms, blood and CSF analysis, neuroimaging features, histopathological characteristics, treatment, and prognosis, were assessed in all patients. According to the results of RT-PCR of BML, all the patients received oral administration of trimethoprim-sulfamethoxazole combined with antiretroviral therapy (ART). Patients were followed up by telephone or outpatient service. Results There were 8 male and 1 female patients; their age ranged from 26 to 56 years-old. The main symptom was intracranial hypertension (6/9). Six patients presented multiple brain lesions, which were mainly located in the supratentorial area (7/9). CD4+ count ranged from 11 to 159 cells/μl (median 92 cells/μl), and serological HIV viral load 0–989190 copies/ml (median 192836 copies/ml). IgG and IgM against serum TG were positive in 7 and 1 patients, respectively. Moreover, regarding CSF, IgG against TG was positive in 3 patients, while all patients were negative for IgM. The neuroimaging features on MRI showed no specificity. Four patients were diagnosed with TE by histopathological findings. After receiving anti-Toxoplasma therapy, 8 (8/9) patients improved clinically to a considerable extent. Conclusions The application of RT-PCR of BML, together with conventional methods, may significantly improve the diagnostic efficiency of TE.

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Clinical relevance of the plasma load of cytomegalovirus in patients infected with HIV—A survival analysis

Cited by 11 publications

References 28 publications

Cerebral toxoplasmosis in HIV-infected patients over 2015–2018 (a case study of Russia)

Cerebral toxoplasmosis in HIV-infected patients over 2015–2018 (a case study of Russia)

Subclinical Cytomegalovirus DNA Is Associated with CD4 T Cell Activation and Impaired CD8 T Cell CD107a Expression in People Living with HIV despite Early Antiretroviral Therapy

Diagnostic value of real-time PCR of brain mass lesion in HIV-associated toxoplasmic encephalitis: a case series

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