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Article ; Online: Immunologic Interplay Between HIV/AIDS and COVID-19: Adding Fuel to the Flames?

Augello, Matteo / Bono, Valeria / Rovito, Roberta / Tincati, Camilla / Marchetti, Giulia

2023 Volume 20, Issue 2, Page(s) 51–75

Abstract: Purpose of review: HIV/AIDS and COVID-19 have been the major pandemics overwhelming our times. Given the enduring immune disfunction featuring people living with HIV (PLWH) despite combination antiretroviral therapy (cART), concerns for higher incidence ...

Abstract	Purpose of review: HIV/AIDS and COVID-19 have been the major pandemics overwhelming our times. Given the enduring immune disfunction featuring people living with HIV (PLWH) despite combination antiretroviral therapy (cART), concerns for higher incidence and severity of SARS-CoV-2 infection as well as for suboptimal responses to the newly developed vaccines in this population arose early during the pandemics. Herein, we discuss the complex interplay between HIV and SARS-CoV-2, with a special focus on the immune responses to SARS-CoV-2 natural infection and vaccination in PLWH. Recent findings: Overall, current literature shows that COVID-19 severity and outcomes may be worse and immune responses to infection or vaccination lower in PLWH with poor CD4 + T-cell counts and/or uncontrolled HIV viremia. Data regarding the risk of post-acute sequelae of SARS-CoV-2 infection (PASC) among PLWH are extremely scarce, yet they seem to suggest a higher incidence of such condition. Scarce immunovirological control appears to be the major driver of weak immune responses to SARS-CoV-2 infection/vaccination and worse COVID-19 outcomes in PLWH. Therefore, such individuals should be prioritized for vaccination and should receive additional vaccine doses. Furthermore, given the potentially higher risk of developing long-term sequelae, PLWH who experienced COVID-19 should be ensured a more careful and prolonged follow-up.
MeSH term(s)	Humans ; COVID-19/complications ; COVID-19/epidemiology ; SARS-CoV-2 ; Post-Acute COVID-19 Syndrome ; HIV Infections/complications ; HIV Infections/drug therapy ; Acquired Immunodeficiency Syndrome ; Disease Progression
Language	English
Publishing date	2023-01-21
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2151206-1
ISSN	1548-3576 ; 1548-3568
ISSN (online)	1548-3576
ISSN	1548-3568
DOI	10.1007/s11904-023-00647-z
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Article ; Online: Editorial: Definition of the immune parameters related to COVID-19 severity.

Tincati, Camilla / de Vries, Rory / Jesenak, Milos / Marchetti, Giulia

Frontiers in immunology

2023 Volume 14, Page(s) 1204125

MeSH term(s)	Humans ; COVID-19/immunology
Language	English
Publishing date	2023-04-27
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1204125
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Article: Failure of CD4+ T-cell Recovery upon Virally-Effective cART: an Enduring Gap in the Understanding of HIV+ Immunological non-Responders.

Bono, Valeria / Augello, Matteo / Tincati, Camilla / Marchetti, Giulia

The new microbiologica

2022 Volume 45, Issue 3, Page(s) 155–172

Abstract: The introduction of cART in the treatment of HIV infection has significantly decreased morbidity and mortality by inducing suppression of viral replication and recovery of CD4+ T-cell counts. How- ever, about 30% of HIV-infected individuals fail to ... ...

Abstract	The introduction of cART in the treatment of HIV infection has significantly decreased morbidity and mortality by inducing suppression of viral replication and recovery of CD4+ T-cell counts. How- ever, about 30% of HIV-infected individuals fail to achieve normalization of CD4+ T-cell counts, de- spite antiretroviral therapy and complete suppression of the HIV load: these patients are referred to as "immunological non-responders". Several studies have shown an increased risk of clinical pro- gression to both AIDS and non-AIDS events as well as a higher mortality in these patients. The pathogenetic factors underlying this condition are multiple and none of these alone can exhaustive- ly explain the mechanism of incomplete immune reconstitution. In light of this, the purpose of the present review is to: i) describe in detail the pathogenetic mechanisms that contribute to scarce immune recovery; ii) discuss the higher morbidity and mortality which feature such a condition; iii) take stock of therapeutic strategies used in recent years for these patients.
MeSH term(s)	Antiretroviral Therapy, Highly Active/adverse effects ; CD4 Lymphocyte Count ; CD4-Positive T-Lymphocytes ; HIV Infections/drug therapy ; Humans ; Viral Load
Language	English
Publishing date	2022-08-03
Publishing country	Italy
Document type	Journal Article ; Review
ZDB-ID	756168-4
ISSN	1121-7138 ; 0391-5352
ISSN	1121-7138 ; 0391-5352
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Article ; Online: Six-month immune responses to mRNA-1273 vaccine in combination antiretroviral therapy treated late presenter people with HIV according to previous SARS-CoV-2 infection.

Augello, Matteo / Bono, Valeria / Rovito, Roberta / Tincati, Camilla / d'Arminio Monforte, Antonella / Marchetti, Giulia

AIDS (London, England)

2023 Volume 37, Issue 10, Page(s) 1503–1517

Abstract: Objective: Immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines in people with HIV (PWH) with a history of late presentation (LP) and their durability have not been fully characterized.: Design: In this ... ...

Abstract	Objective: Immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccines in people with HIV (PWH) with a history of late presentation (LP) and their durability have not been fully characterized. Design: In this prospective, longitudinal study, we sought to assess T-cell and humoral responses to SARS-CoV-2 mRNA vaccination up to 6 months in LP-PWH on effective combination antiretroviral therapy (cART) as compared to HIV-negative healthcare workers (HCWs), and to evaluate whether previous SARS-CoV-2 infection modulates immune responses to vaccine. Methods: SARS-CoV-2 spike (S)-specific T-cell responses were determined by two complementary flow cytometry methodologies, namely activation-induced marker (AIM) assay and intracellular cytokine staining (ICS), whereas humoral responses were measured by ELISA [anti-receptor binding domain (RBD) antibodies) and receptor-binding inhibition assay (spike-ACE2 binding inhibition activity), before vaccination (T0), 1 month (T1) and 5 months (T2) after the second dose. Results: LP-PWH showed at T1 and T2 significant increase of: S-specific memory and circulating T follicular helper (cTfh) CD4 + T cells; polyfunctional Th1-cytokine (IFN-γ, TNF-α, IL-2)- and Th2-cytokine (IL-4)-producing S-specific CD4 + T cells; anti-RBD antibodies and spike-ACE2 binding inhibition activity. Immune responses to vaccine in LP-PWH were not inferior to HCWs overall, yet S-specific CD8 + T cells and spike-ACE2 binding inhibition activity correlated negatively with markers of immune recovery on cART. Interestingly, natural SARS-CoV-2 infection, while able to sustain S-specific antibody response, seems less efficacious in inducing a T-cell memory and in boosting immune responses to vaccine, possibly reflecting an enduring partial immunodeficiency. Conclusions: Altogether, these findings support the need for additional vaccine doses in PWH with a history of advanced immune depression and poor immune recovery on effective cART.
MeSH term(s)	Humans ; COVID-19/prevention & control ; 2019-nCoV Vaccine mRNA-1273 ; SARS-CoV-2 ; Angiotensin-Converting Enzyme 2 ; Antiretroviral Therapy, Highly Active ; Longitudinal Studies ; Prospective Studies ; HIV Infections/drug therapy ; Cytokines
Chemical Substances	2019-nCoV Vaccine mRNA-1273 (EPK39PL4R4) ; Angiotensin-Converting Enzyme 2 (EC 3.4.17.23) ; Cytokines
Language	English
Publishing date	2023-05-18
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639076-6
ISSN	1473-5571 ; 0269-9370 ; 1350-2840
ISSN (online)	1473-5571
ISSN	0269-9370 ; 1350-2840
DOI	10.1097/QAD.0000000000003585
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Article ; Online: Detection of human papillomavirus in fresh and dried urine through an automated system for cervical cancer screening in low- and middle-income countries.

Tanzi, Elisabetta / Bianchi, Silvia / Fappani, Clara / Gori, Maria / Colzani, Daniela / Passera, Ilaria / Tincati, Camilla / Canuti, Marta / Raviglione, Mario / Amendola, Antonella

Journal of medical virology

2023 Volume 95, Issue 5, Page(s) e28802

Abstract: The majority of cervical cancer cases and associated deaths occur in low- and middle-income countries (LMICs), where sociocultural barriers, poor access to prevention and care, and technical and practical difficulties hinder screening coverage ... ...

Abstract	The majority of cervical cancer cases and associated deaths occur in low- and middle-income countries (LMICs), where sociocultural barriers, poor access to prevention and care, and technical and practical difficulties hinder screening coverage improvement. Using urine specimens for human papillomaviruses (HPV) molecular screening through automated testing platforms can help to overcome these problems. We evaluated the high-risk (HR) HPV detection performance of the Xpert® HPV test on GeneXpert® System (Cepheid), on fresh and dried urine (Dried Urine Spot [DUS]) samples as compared to an in-house polymerase chain reaction (PCR) genotyping assay. Forty-five concentrated urine samples collected from women with known cytological and HPV infection status, determined through in-house PCR and genotyping assays, were tested "as is" and as DUS with the Xpert® HPV test. This system detected HR-HPV in 86.4% of fresh and in 77.3% of dried urine samples collected from HPV+ women, correctly identifying HR-HPV infection in 100% of women with low- and high-grade lesions. High concordance (91.4%, k = 0.82) was found between PCR test and Xpert® HPV Test from urine. Urine-based Xpert® HPV test seems to be a suitable screening test for detection of HR-HPV infections associated with low- and high-grade lesions requiring follow-up monitoring or treatment. This methodology, relying on noninvasively collected samples and on available rapid testing platforms, could facilitate large, at-scale screening programs, particularly in LMICs and rural areas, thus reducing adverse outcomes of HPV infection and facilitating achievement of the WHO cervical cancer elimination goal.
MeSH term(s)	Female ; Humans ; Uterine Cervical Neoplasms/diagnosis ; Human Papillomavirus Viruses ; Papillomavirus Infections/diagnosis ; Developing Countries ; Early Detection of Cancer/methods ; Papillomaviridae/genetics ; Mass Screening/methods ; DNA, Viral/analysis
Chemical Substances	DNA, Viral
Language	English
Publishing date	2023-05-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	752392-0
ISSN	1096-9071 ; 0146-6615
ISSN (online)	1096-9071
ISSN	0146-6615
DOI	10.1002/jmv.28802
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Article: HIV-Related Oral Mucosa Lesions: A Cross-Sectional Study on a Cohort of Italian Patients.

Tarozzi, Marco / Baruzzi, Elisa / Decani, Sem / Tincati, Camilla / Santoro, Andrea / Moneghini, Laura / Lodi, Giovanni / Sardella, Andrea / Carrassi, Antonio / Varoni, Elena Maria

Biomedicines

2024 Volume 12, Issue 2

Abstract: Background: Human immunodeficiency virus (HIV) infection can be associated with oral mucosal diseases, including oral candidiasis and HPV infection, which are putative indicators of the immune status.: Aim and methods: This retrospective cross- ... ...

Abstract	Background: Human immunodeficiency virus (HIV) infection can be associated with oral mucosal diseases, including oral candidiasis and HPV infection, which are putative indicators of the immune status. Aim and methods: This retrospective cross-sectional study was aimed at assessing the prevalence of HIV-related oral mucosal lesions in a cohort of Italian HIV+ patients regularly attending the Clinics of Infectious Diseases. Results: One hundred seventy-seven (n = 177) patients were enrolled and 30 (16.9%) of them showed HIV-related diseases of the oral mucosa. They were mainly found in male patients over 35 years old, undergoing Combination Antiretroviral Therapy (cART), and with CD4+ count < 500/µL. Oral candidiasis was the most common HIV-related oral lesion. No significant correlations could be detected between the prevalence of HPV infection and other clinical parameters (lymphocyte count, cART treatment and viral load). Conclusions: HIV-related oral mucosal diseases can correlate with immunosuppression. Early diagnosis and management of oral lesions in HIV+ patients should be part of the regular follow-up, from a multidisciplinary perspective of collaboration between oral medicine and infectious disease specialists, in an attempt to reduce morbidity due to oral lesions and modulate antiretroviral therapy according to the patient's immune status.
Language	English
Publishing date	2024-02-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines12020436
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Article: Biomarkers of aging in HIV: inflammation and the microbiome.

Tincati, Camilla / Merlini, Esther / Ancona, Giuseppe / Marchetti, Giulia

European geriatric medicine

2018 Volume 10, Issue 2, Page(s) 175–182

Abstract: Purpose: HIV-infected subjects present increased levels of inflammatory cytokines and T cell activation in the peripheral blood despite suppressive combination antiretroviral therapy which renders them susceptible to premature aging. The purpose of the ... ...

Abstract	Purpose: HIV-infected subjects present increased levels of inflammatory cytokines and T cell activation in the peripheral blood despite suppressive combination antiretroviral therapy which renders them susceptible to premature aging. The purpose of the present work was to review existing evidence on the ways in which the anatomical and microbiological abnormalities of the gastrointestinal tract can represent a major cause of organ disease in HIV infection. Methods: We conducted a systematic review of the Pubmed database for articles published from 2014 to 2018. We included studies on inflammatory/activation biomarkers associated with cardiovascular and bone disease, neurocognitive impairment and serious non-AIDS events in HIV-infected subjects. We also included researches which linked peripheral inflammation/activation to the anatomical, immune and microbiological alterations of the gastrointestinal tract. Results: Recent literature data confirm the association between non-infectious comorbidities and inflammation in HIV infection which may be driven by gastrointestinal tract abnormalities, specifically microbial translocation and dysbiosis. Furthermore, there is mounting evidence on the possible role of metabolic functions of the microbiota in the pathogenesis of premature aging in the HIV-infected population. Conclusions: Biomarkers need to be validated for their use in the management of HIV infection. Compounds which counteract microbial translocation, inflammation and dysbiosis have been investigated as alternative therapeutic strategies in viro-suppressed HIV-infected individuals, but appear to have limited efficacy, probably due to the multifactorial pathogenesis of non-infectious comorbidities in this setting.
Language	English
Publishing date	2018-12-06
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2556794-9
ISSN	1878-7657 ; 1878-7649
ISSN (online)	1878-7657
ISSN	1878-7649
DOI	10.1007/s41999-018-0145-0
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Article ; Online: Performance evaluation of a self-administered point-of-care test for anal HPV screening in PrEP users: data from a community-based PrEP service.

Biasioli, Lorenzo / Rossotti, Roberto / Tavelli, Alessandro / De Bona, Anna / Tincati, Camilla / Calzavara, Daniele / Vinti, Pietro / Baiguera, Chiara / D'Amico, Federico / Nava, Alice / Repossi, Roberto / Bossolasco, Simona / Muccini, Camilla / Mulè, Giovanni / Tesoro, Daniele / d'Arminio Monforte, Antonella / Cernuschi, Massimo

Sexually transmitted infections

2024

Abstract: Objectives: In this study, we compared the performance of a self-administered point-of-care test (POCT) for anal human papillomavirus (HPV) screening with laboratory gold-standard test in pre-exposure prophylaxis (PrEP) users and evaluated its ... ...

Abstract	Objectives: In this study, we compared the performance of a self-administered point-of-care test (POCT) for anal human papillomavirus (HPV) screening with laboratory gold-standard test in pre-exposure prophylaxis (PrEP) users and evaluated its feasibility. Methods: We enrolled PrEP users from a local community-based PrEP service. Each participant self-collected an anal swab to test anal HPV with a PCR POCT capable of detecting 14 high-risk HPV genotypes. Anonymous questionnaires on self-sampling feasibility were completed. Participants were then referred to local clinics to undergo standard viral genotyping. Concordance between POCT and gold-standard test was measured with absolute agreement and Cohen's kappa. Receiver operating characteristic (ROC) curves were used to calculate POCT sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Results: 179 subjects got a valid POCT result, most of them men (98.3%) and men who have sex with men (90.4%). 68.2% tested positive for at least one high-risk HPV genotype on POCT. 150 feasibility questionnaires were collected: 92.7% of compilers found the self-swab easy to perform. For 178 subjects, a gold-standard test valid result was also available: 77% tested positive for at least one high-risk HPV genotype. The median time elapsed between the two tests was 9.8 months, due to COVID-19-related service interruptions. Agreement between POCT and gold-standard test was 79.3% (Cohen's kappa=0.49). POCT showed a sensitivity of 81.0%, a specificity of 73.8%, a PPV of 91.0% and an NPV of 54.4%. Conclusions: POCT showed a moderate agreement with gold-standard test and a discrete sensitivity and specificity, suggesting that it could be a useful and feasible additional tool for HPV screening, especially in low-resource and community-based settings.
Language	English
Publishing date	2024-04-19
Publishing country	England
Document type	Journal Article
ZDB-ID	1420303-0
ISSN	1472-3263 ; 1368-4973
ISSN (online)	1472-3263
ISSN	1368-4973
DOI	10.1136/sextrans-2023-055939
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Article: Gamma-Delta T-Cell Phenotype and Function in DAA-Treated HIV-HCV Co-Infected and HCV-Mono-Infected Subjects

Bono, Valeria / Tincati, Camilla / Van Den Bogaart, Lorena / Cannizzo, Elvira Stefania / Rovito, Roberta / Augello, Matteo / De Bona, Anna / D’Arminio Monforte, Antonella / Milazzo, Laura / Marchetti, Giulia

Viruses. 2022 July 22, v. 14, no. 8

2022

Abstract: HIV-HCV co-infected subjects are at risk of liver fibrosis which may be linked to immune imbalances. Direct-acting antivirals (DAAs) represent the mainstay of HCV treatment in co-infected individuals, yet their effects on immune cell populations playing ... ...

Abstract	HIV-HCV co-infected subjects are at risk of liver fibrosis which may be linked to immune imbalances. Direct-acting antivirals (DAAs) represent the mainstay of HCV treatment in co-infected individuals, yet their effects on immune cell populations playing a role in fibrogenesis is unknown. We assessed γδ T-cell phenotype and function, Treg and Th17 frequencies, as well as γ-globulins and B-cell activation in 47 HIV-HCV co-infected and 35 HCV mono-infected individuals prior to and following DAA treatment (SVR12). Γδ T-cell activation decreased in both groups yet persisted at higher levels in the HIV-HCV co-infected subjects. No differences were registered in terms of γδT-cell function. Of note, the Vδ2/Th17 ratio, inversely linked to liver damage, increased significantly in the two groups upon treatment, yet a negative correlation between the Vδ2/Th17 ratio and liver function enzymes was found in the co-infected subjects alone. B-cell activation and γ-globulin levels decreased in both settings, yet B-cell activation remained higher in the HIV-HCV co-infected individuals. In HIV-HCV co-infected and HCV mono-infected participants, the effect of DAA was limited to γδ T- and B-cell activation as well as γ-globulin concentrations and the Vδ2/Th17 ratio, with no changes in γδ T-cell function and Treg frequencies. Importantly, γδ T- and B-cell activation remained at higher levels in the co-infected individuals than in those with HCV mono-infection alone. The persistence of such alterations within these cell subsets may be associated with the risk of hepatic and extrahepatic complications.
Keywords	B-lymphocytes ; T-lymphocytes ; antiviral agents ; liver ; liver cirrhosis ; liver function ; mixed infection ; phenotype ; risk
Language	English
Dates of publication	2022-0722
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2516098-9
ISSN	1999-4915
ISSN	1999-4915
DOI	10.3390/v14081594
Database	NAL-Catalogue (AGRICOLA)

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Article: Do Combination Antiretroviral Therapy Regimens for HIV Infection Feature Diverse T-Cell Phenotypes and Inflammatory Profiles?

Tincati, Camilla / Mondatore, Debora / Bai, Francesca / d'Arminio Monforte, Antonella / Marchetti, Giulia

Open forum infectious diseases

2020 Volume 7, Issue 9, Page(s) ofaa340

Abstract: Immune abnormalities featuring HIV infection persist despite the use of effective combination antiretroviral therapy (cART) and may be linked to the development of noninfectious comorbidities. The aim of the present narrative, nonsystematic literature ... ...

Abstract	Immune abnormalities featuring HIV infection persist despite the use of effective combination antiretroviral therapy (cART) and may be linked to the development of noninfectious comorbidities. The aim of the present narrative, nonsystematic literature review is to understand whether cART regimens account for qualitative differences in immune reconstitution. Many studies have reported differences in T-cell homeostasis, inflammation, coagulation, and microbial translocation parameters across cART classes and in the course of triple vs dual regimens, yet such evidence is conflicting and not consistent. Possible reasons for discrepant results in the literature are the paucity of randomized controlled clinical trials, the relatively short follow-up of observational studies, the lack of clinical validation of the numerous inflammatory biomarkers utilized, and the absence of research on the effects of cART in tissues. We are currently thus unable to establish if cART classes and regimens are truly accountable for the differences observed in immune/inflammation parameters in different clinical settings. Questions still remain as to whether an early introduction of cART, specifically in the acute stage of disease, or newer drugs and novel dual drug regimens are able to significantly impact the quality of immune reconstitution and the risk of disease progression in HIV-infected subjects.
Language	English
Publishing date	2020-08-13
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2757767-3
ISSN	2328-8957
ISSN	2328-8957
DOI	10.1093/ofid/ofaa340
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