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Article ; Online: Human and Viral microRNA Expression in Acute and Chronic HIV Infections.

Lazzari, Elisabetta / Rozera, Gabriella / Gagliardini, Roberta / Esvan, Rozenn / Mondi, Annalisa / Mazzotta, Valentina / Camici, Marta / Girardi, Enrico / Antinori, Andrea / Maggi, Fabrizio / Abbate, Isabella

Viruses

2024 Volume 16, Issue 4

Abstract: Human and viral microRNAs (miRNAs) are involved in the regulation of gene transcription, and the establishment of their profiles in acute (AHI) and chronic (CHI) HIV infections may shed light on the pathogenetic events related to different phases of HIV ... ...

Abstract	Human and viral microRNAs (miRNAs) are involved in the regulation of gene transcription, and the establishment of their profiles in acute (AHI) and chronic (CHI) HIV infections may shed light on the pathogenetic events related to different phases of HIV disease. Next-generation sequencing (NGS) of miRNA libraries was performed, and the reads were used to analyze miRNA differential expression in the plasma with AHI and CHI. Functional analysis was then undertaken to investigate the biological processes characterizing the two phases of HIV infection. Except for hsa-miR-122-5p, which was found in 3.39% AHI vs. 0.18% CHI, the most represented human miRNAs were similarly represented in AHI and CHI. However, when considering the overall detected miRNAs in AHI and CHI, 15 displayed differential expression (FDR
MeSH term(s)	Humans ; MicroRNAs/genetics ; HIV Infections/virology ; HIV Infections/genetics ; RNA, Viral/genetics ; High-Throughput Nucleotide Sequencing ; Gene Expression Profiling ; Male ; Adult ; Female ; Acute Disease ; Chronic Disease ; Middle Aged ; HIV-1/genetics ; Immunity, Innate ; Gene Expression Regulation
Chemical Substances	MicroRNAs ; RNA, Viral
Language	English
Publishing date	2024-03-23
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v16040496
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Article ; Online: Persistent poor clinical outcomes of people living with HIV presenting with AIDS and late HIV diagnosis - results from the ICONA cohort in Italy, 2009-2022.

Mondi, Annalisa / Cozzi-Lepri, Alessandro / Tavelli, Alessandro / Cingolani, Antonella / Giacomelli, Andrea / Orofino, Giancarlo / De Girolamo, Gabriella / Pinnetti, Carmela / Gori, Andrea / Saracino, Annalisa / Bandera, Alessandra / Marchetti, Giulia / Girardi, Enrico / Mussini, Cristina / d'Arminio Monforte, Antonella / Antinori, Andrea

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases

2024 Volume 142, Page(s) 106995

Abstract: Objectives: Limited data are available on the long-term outcomes in recent years for late HIV diagnosis (LD).: Methods: All subjects with HIV enrolled in the ICONA cohort in 2009-2022 who started antiretroviral treatment (ART) within 4 months from ... ...

Abstract	Objectives: Limited data are available on the long-term outcomes in recent years for late HIV diagnosis (LD). Methods: All subjects with HIV enrolled in the ICONA cohort in 2009-2022 who started antiretroviral treatment (ART) within 4 months from diagnosis were included and divided into: (i) pre-ART CD4 count ≥350/mm Results: Of 6813 participants (2448 non-LD, 3198 LD asymptomatic, and 1167 LD-AIDS), 161 (2.4%) died after ART initiation. At survival analysis, a higher probability of all-cause mortality has been identified for LD than non-LD (P <0.001) and within the former, for LD-AIDS over LD asymptomatic (P <0.001). After adjusting for confounders, LD showed a higher risk of all-cause mortality (vs non-LD adjusted hazard ratio (aHR) 5.51, P <0.001) and, in particular, being an AIDS presenter predicted a greater risk of all-cause (aHR = 4.42, P <0.001), AIDS-related (adjusted subhazard ratio [aSHR] = 16.86, P <0.001), and non-AIDS-related mortality (aSHR = 1.74, P = 0.022) than the rest of the late presenters. Among the short-term survivors in the LD-AIDS group, the long-term mortality was mediated by the lack of immune recovery at 2 years. Finally, LD compared with non-LD and, particularly, among the former, LD-AIDS over LD asymptomatic showed a greater risk of treatment failure. Conclusions: In recent years, LD subjects, particularly, AIDS presenters, remained at a higher risk of poorer outcomes. Public health strategies for early HIV diagnosis are urgently needed to constrain the mortality gap.
MeSH term(s)	Humans ; Acquired Immunodeficiency Syndrome/complications ; Acquired Immunodeficiency Syndrome/diagnosis ; Acquired Immunodeficiency Syndrome/drug therapy ; HIV Infections/complications ; HIV Infections/diagnosis ; HIV Infections/drug therapy ; CD4 Lymphocyte Count ; Anti-Retroviral Agents/therapeutic use ; Italy/epidemiology ; Anti-HIV Agents/therapeutic use
Chemical Substances	Anti-Retroviral Agents ; Anti-HIV Agents
Language	English
Publishing date	2024-03-06
Publishing country	Canada
Document type	Journal Article
ZDB-ID	1331197-9
ISSN	1878-3511 ; 1201-9712
ISSN (online)	1878-3511
ISSN	1201-9712
DOI	10.1016/j.ijid.2024.106995
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Article: A Case of Severe Mpox Complicated with

Di Bari, Silvia / Mondi, Annalisa / Pinnetti, Carmela / Mazzotta, Valentina / Carletti, Fabrizio / Matusali, Giulia / Vincenti, Donatella / Gagliardini, Roberta / Santoro, Raffaele / Fontana, Carla / Maggi, Fabrizio / Girardi, Enrico / Vaia, Francesco / Antinori, Andrea

Pathogens (Basel, Switzerland)

2023 Volume 12, Issue 9

Abstract: Since May 2022, a global outbreak of human Mpox has rapidly spread in non-endemic countries. We report a case of a 34-year-old man admitted to hospital for a six-day history of fever associated with vesiculo-pustular rash involving the face, limbs, trunk ...

Abstract	Since May 2022, a global outbreak of human Mpox has rapidly spread in non-endemic countries. We report a case of a 34-year-old man admitted to hospital for a six-day history of fever associated with vesiculo-pustular rash involving the face, limbs, trunk and perianal region, lymphadenopathy and severe proctitis and pharyngitis. He was HIV-positive and virologically suppressed by stable antiretroviral therapy. On admission, Mpox virus-specific RT-PCR was positive from multiple samples. Additionally, blood cultures yielded
Language	English
Publishing date	2023-08-23
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2695572-6
ISSN	2076-0817
ISSN	2076-0817
DOI	10.3390/pathogens12091073
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Article ; Online: Tecovirimat concentrations and viral suppression in seminal fluid from patients with mpox.

Tempestilli, Massimo / Mondi, Annalisa / Matusali, Giulia / Mariotti, Davide / Pinnetti, Carmela / Beccacece, Alessia / Cimini, Eleonora / Mazzotta, Valentina / Carletti, Fabrizio / Faccendini, Paolo / Maggi, Fabrizio / Girardi, Enrico / Nicastri, Emanuele / Vaia, Francesco / Antinori, Andrea

The Lancet. Infectious diseases

2023 Volume 23, Issue 5, Page(s) 531–532

MeSH term(s)	Humans ; Mpox (monkeypox) ; Fetus
Language	English
Publishing date	2023-03-30
Publishing country	United States
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	2061641-7
ISSN	1474-4457 ; 1473-3099
ISSN (online)	1474-4457
ISSN	1473-3099
DOI	10.1016/S1473-3099(23)00214-1
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Zs.A 5743: Show issues

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Article ; Online: Kinetics of TTV Loads in Peripheral Blood Mononuclear Cells of Early Treated Acute HIV Infections.

Abbate, Isabella / Rozera, Gabriella / Cimini, Eleonora / Carletti, Fabrizio / Tartaglia, Eleonora / Rubino, Marika / Pittalis, Silvia / Esvan, Rozenn / Gagliardini, Roberta / Mondi, Annalisa / Mazzotta, Valentina / Camici, Marta / Girardi, Enrico / Vaia, Francesco / Puro, Vincenzo / Antinori, Andrea / Maggi, Fabrizio

Viruses

2023 Volume 15, Issue 9

Abstract: Torquetenovirus (TTV) is the most abundant component of the human blood virome and its replication is controlled by a functioning immune system. In this study, TTV replication was evaluated in 21 people with acute HIV infection (AHI) and immune ... ...

Abstract	Torquetenovirus (TTV) is the most abundant component of the human blood virome and its replication is controlled by a functioning immune system. In this study, TTV replication was evaluated in 21 people with acute HIV infection (AHI) and immune reconstitution following antiretroviral therapy (ART). PBMC-associated TTV and HIV-1 DNA, as well as plasma HIV-1 RNA, were measured by real-time PCR. CD4 and CD8 differentiation, activation, exhaustion, and senescence phenotypes were analyzed by flow cytometry. Thirteen healthy donors (HD) and twenty-eight chronically infected HIV individuals (CHI), late presenters at diagnosis, were included as control groups. TTV replication in AHI seems to be controlled by the immune system being higher than in HD and lower than in CHI. During ART, a transient increase in TTV DNA levels was associated with a significant perturbation of activation and senescence markers on CD8 T cells. TTV loads were positively correlated with the expansion of CD8 effector memory and CD57+ cells. Our results shed light on the kinetics of TTV replication in the context of HIV acute infection and confirm that the virus replication is strongly regulated by the modulation of the immune system.
MeSH term(s)	Humans ; HIV Infections ; Leukocytes, Mononuclear ; Torque teno virus/genetics ; HIV-1/genetics ; DNA
Chemical Substances	DNA (9007-49-2)
Language	English
Publishing date	2023-09-15
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v15091931
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Article ; Online: Temporal intra-host variability of mpox virus genomes in multiple body tissues.

Journal of medical virology

2023 Volume 95, Issue 5, Page(s) e28791

Abstract: Whole-genome sequencing (WGS) has been widely used for the genomic characterization and the phylogenesis of mpox virus (MPXV) 2022 multi-country outbreak. To date, no evidence has been reported on intra-host evolution within samples collected over time ... ...

Abstract	Whole-genome sequencing (WGS) has been widely used for the genomic characterization and the phylogenesis of mpox virus (MPXV) 2022 multi-country outbreak. To date, no evidence has been reported on intra-host evolution within samples collected over time from a single patient with long-term infection. Fifty-one samples were collected from five patients at different time points post-symptom onset. All samples were confirmed as MPXV DNA positive, amplified by a multiplexed PCR amplicon, and sequenced by WGS. Complete MPXV genomes were assembled by reference mapping and then aligned to perform phylogenetic and hierarchical clustering analysis. Large intra-host variability was observed among the MPXV genomes sequenced from samples of two immunocompromised with advanced HIV-1 infection patients with prolonged MPXV shedding. Overall, 20 nucleotide mutations were identified in the 32 genomes from HIV patients, differently distributed in samples collected from different tissues and at different time points. No sequence compartmentalization nor variation was observed in the three patients with rapid viral clearance. MPXV exhibits adaptation to changing environments within the infected host and consequently demonstrates tissue compartmentalization. Further studies are needed to elucidate the role of this adaptation in forming a pool of genetic variability and contributing to viral persistence and its clinical implications.
MeSH term(s)	Humans ; HIV Infections ; Mpox (monkeypox) ; Phylogeny ; Genome, Viral ; Cluster Analysis
Language	English
Publishing date	2023-05-25
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	752392-0
ISSN	1096-9071 ; 0146-6615
ISSN (online)	1096-9071
ISSN	0146-6615
DOI	10.1002/jmv.28791
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Zs.A 1320: Show issues

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Article ; Online: Pharmacokinetics of tecovirimat in subjects with Mpox.

Tempestilli, Massimo / Mondi, Annalisa / D'Avolio, Antonio / Forini, Olindo / Pinnetti, Carmela / Mazzotta, Valentina / Gagliardini, Roberta / Beccacece, Alessia / De Nicolò, Amedeo / Faccendini, Paolo / Cimini, Eleonora / Maggi, Fabrizio / Girardi, Enrico / Nicastri, Emanuele / Boffito, Marta / Vaia, Francesco / Antinori, Andrea

International journal of antimicrobial agents

2023 Volume 63, Issue 2, Page(s) 107068

Abstract: Objective: To investigate the pharmacokinetics (PK) of tecovirimat in subjects with Mpox.: Methods: This monocentric, prospective, observational study enrolled subjects with Mpox who received standard treatment with oral tecovirimat. Plasma samples ... ...

Abstract	Objective: To investigate the pharmacokinetics (PK) of tecovirimat in subjects with Mpox. Methods: This monocentric, prospective, observational study enrolled subjects with Mpox who received standard treatment with oral tecovirimat. Plasma samples for PK assessment were collected at steady state (5-8 days after initiation of antiviral therapy), before and 3, 5, 7 and 12 h after tecovirimat administration. Drug concentrations were determined by validated liquid chromatography coupled with tandem mass spectrometry. PK parameters were calculated using Phoenix 8.1. Results: Overall, 14 male patients hospitalized for severe Mpox with ongoing tecovirimat treatment were enrolled in this study. Six of the 14 patients were living with human immunodeficiency virus (HIV), all of whom were on antiretroviral therapy (ART) and virologically suppressed at the time of hospitalization. Significant differences in tecovirimat PK were observed in subjects without HIV compared with subjects with HIV. In subjects with HIV, the maximum tecovirimat plasma concentration (39%, P≤0.0001), minimum tecovirimat plasma concentration (42%, P=0.0079) and area under the curve from zero to the last measured time-point (40%, P≤0.0001) were significantly lower compared with subjects without HIV, but all concentrations remained above the in-vitro calculated 90% inhibitory concentration. No significant associations were found between demographic/clinical data and tecovirimat PK. All patients recovered completely within 14 (range 6-36) days of treatment initiation. Conclusions: This study found a significant decrease in plasma exposure of tecovirimat in Mpox patients with HIV on effective ART compared with those without HIV, with no evident impact on clinical outcomes. Although these results need to be confirmed in larger studies, they may provide useful information on the PK of tecovirimat.
MeSH term(s)	Humans ; Male ; Prospective Studies ; Mpox (monkeypox) ; HIV Infections/drug therapy ; HIV
Language	English
Publishing date	2023-12-22
Publishing country	Netherlands
Document type	Observational Study ; Journal Article
ZDB-ID	1093977-5
ISSN	1872-7913 ; 0924-8579
ISSN (online)	1872-7913
ISSN	0924-8579
DOI	10.1016/j.ijantimicag.2023.107068
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Zs.A 3368: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Long-term outcome of dolutegravir-containing regimens according to sex: data from the ICONA study.

D'arminio Monforte, Antonella / Tavelli, Alessandro / Sala, Matteo / Mondi, Annalisa / Rusconi, Stefano / Antinori, Spinello / Puoti, Massimo / Celesia, Benedetto Maurizio / Taramasso, Lucia / Saracino, Annalisa / Antinori, Andrea / Cozzi-Lepri, Alessandro

The Journal of antimicrobial chemotherapy

2022 Volume 78, Issue 4, Page(s) 933–945

Abstract: Objectives: To compare the long-term risk of treatment failure of dolutegravir-based ART in men and women in a real-life setting.: Patients and methods: Persons living with HIV (PLWH) from the ICONA cohort were included if they had started ... ...

Abstract	Objectives: To compare the long-term risk of treatment failure of dolutegravir-based ART in men and women in a real-life setting. Patients and methods: Persons living with HIV (PLWH) from the ICONA cohort were included if they had started dolutegravir in a two- or three-drug regimen as ART-naive or as virologically controlled ART-experienced. The primary endpoint was time to treatment failure (virological/clinical failure or dolutegravir discontinuation). Secondary endpoints were: time to dolutegravir discontinuation due to toxicity and to neuropsychiatric adverse events; and time to virological failure. Cox regression analyses focused on differences in outcomes by sex. Results: A total of 2304 PLWH (15% women) initiated dolutegravir-based therapy from ART-naive, and 1916 (19.8% women) while experienced. After a median follow-up of 2.2 (IQR: 0.9-3.9) years in ART-naive and 2.4 (IQR: 1.1-4.3) years in experienced, the 4-year cumulative probability of treatment failure was 33% (95% CI 30.5-35.1) and 20% (95% CI 17.8-22.3), respectively. In the multivariable analyses, in ART-naive the risk of treatment failure was higher for women, but not different after excluding women discontinuing dolutegravir for pregnancy concerns. We also observed a higher risk of discontinuation for toxicity in women (ART-naives: Adjusted Hazard Ratio (AHR): 1.56%; 95% CI: 1.03-2.37; ART-experienced: AHR: 1.53%; 95% CI: 1.01-2.32), although the absolute 4-year probability was low: 7.7% (95% CI 6.5-9.2) in ART-naive and 8.3% (95% CI 6.9-9.9) in experienced. Conclusions: In our cohort of PLWH treated with dolutegravir-based regimens and followed up for up to 4 years, we observed a low risk of treatment failure and no evidence for a difference by sex, after excluding discontinuation due to pregnancy concerns. However, we observed a higher risk of dolutegravir discontinuation for toxicity in women.
MeSH term(s)	Male ; Pregnancy ; Humans ; Female ; HIV Infections/drug therapy ; Oxazines/therapeutic use ; Heterocyclic Compounds, 3-Ring/adverse effects ; Piperazines/adverse effects ; Pyridones/therapeutic use ; Anti-HIV Agents/adverse effects ; Viral Load
Chemical Substances	dolutegravir (DKO1W9H7M1) ; Oxazines ; Heterocyclic Compounds, 3-Ring ; Piperazines ; Pyridones ; Anti-HIV Agents
Language	English
Publishing date	2022-10-13
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	191709-2
ISSN	1460-2091 ; 0305-7453
ISSN (online)	1460-2091
ISSN	0305-7453
DOI	10.1093/jac/dkad026
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Zs.A 1197: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Kinetics of viral DNA in body fluids and antibody response in patients with acute Monkeypox virus infection.

iScience

2023 Volume 26, Issue 3, Page(s) 106102

Abstract: We report the follow-up laboratory investigation of three MPXV cases infected in May-June 2022 from diagnosis to disease resolution, monitoring viral shedding in different body fluids and antibody kinetics. Out of 138 non-lesion samples, viral DNA was ... ...

Abstract	We report the follow-up laboratory investigation of three MPXV cases infected in May-June 2022 from diagnosis to disease resolution, monitoring viral shedding in different body fluids and antibody kinetics. Out of 138 non-lesion samples, viral DNA was found in 92.3% saliva, 85.7% semen, 86.2% oropharyngeal swabs, 51.7% plasma, 46.1% stool, and 9.5% urine samples. Viral load quantified by digital PCR widely varied, but tend to be higher in oropharyngeal swabs, saliva, and stool. Replication competent virus was recovered from four out of seventeen samples, including 1 saliva, 1 oropharyngeal swabs, 1 semen, and 1 stool. The analysis of the antibody kinetics revealed that IgM, IgA, and IgG antibodies were detected within two weeks post-symptoms onset for all three patients, with IgG detected early on at day 4-8 and IgM and IgA showing lower titers along the time frame of the study. Antibody levels increased during the second week of illness with IgG reaching high titers.
Language	English
Publishing date	2023-02-01
Publishing country	United States
Document type	Journal Article
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2023.106102
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Article ; Online: Use of Pembrolizumab for Treatment of Progressive Multifocal Leukoencephalopathy in People Living with HIV.

Pinnetti, Carmela / Cimini, Eleonora / Vergori, Alessandra / Mazzotta, Valentina / Grassi, Germana / Mondi, Annalisa / Forbici, Federica / Amendola, Alessandra / Grisetti, Susanna / Baldini, Francesco / Candela, Caterina / Casetti, Rita / Campioni, Paolo / Capobianchi, Maria Rosaria / Agrati, Chiara / Antinori, Andrea

Viruses

2022 Volume 14, Issue 5

Abstract: Progressive Multifocal Leukoencephalopathy (PML) is a demyelinating disease occurring in advanced HIV infection, caused by the reactivation of poliomavirus JC (JCV). The use of pembrolizumab for treatment is based on the inhibition of programmed cell ... ...

Abstract	Progressive Multifocal Leukoencephalopathy (PML) is a demyelinating disease occurring in advanced HIV infection, caused by the reactivation of poliomavirus JC (JCV). The use of pembrolizumab for treatment is based on the inhibition of programmed cell death protein 1 (PD-1), potentially improving the anti JCV-specific response. We used pembrolizumab with combined antiretroviral treatment (cART) on a compassionate-use basis. At each administration, clinical evaluation, MRI and laboratory testing, including CD3, CD4, CD8, PD-1 markers, HIV-RNA and JCV-DNA in cerebrospinal fluid (CSF)/plasma pairs, were performed. The JCV-specific T cell response was analysed by Elispot assay. This study included five HIV patients: four male, median age 43 years (29-52), median CD4 and CD8 count 150 (15-158) and 973 (354-1250) cell/mm
MeSH term(s)	Adult ; Antibodies, Monoclonal, Humanized/therapeutic use ; DNA, Viral/genetics ; HIV Infections/complications ; HIV Infections/drug therapy ; Humans ; JC Virus ; Leukoencephalopathy, Progressive Multifocal/drug therapy ; Leukoencephalopathy, Progressive Multifocal/virology ; Male ; Middle Aged ; Polyomavirus Infections/complications ; Polyomavirus Infections/drug therapy ; Programmed Cell Death 1 Receptor/antagonists & inhibitors ; RNA, Viral ; Virus Activation
Chemical Substances	Antibodies, Monoclonal, Humanized ; DNA, Viral ; Programmed Cell Death 1 Receptor ; RNA, Viral ; pembrolizumab (DPT0O3T46P)
Language	English
Publishing date	2022-05-05
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v14050970
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