Massimo Galli - Academia.edu (original) (raw)

Papers by Massimo Galli

Immunology Today, 1996

n a seminal paper published in 1986, Jay Levy and colleagues demonstrated that soluble factors de... more n a seminal paper published in 1986, Jay Levy and colleagues demonstrated that soluble factors derived from CDP T cells are capable of suppressing the replication of human immunodeficiency virus (HIV) in peripheral blood mononuclear cells (PBMCs)'. The fundamental implication of this observation was that HIV infection might be influenced and controlled by a cellular immune response that is not dependent on a classic cytotoxic mechanism. The CD8' T-cell antiviral factor (CAF) has since become a 1..-1wn Holy Grail for AIDS researchers, eluding frustrating attempts at identification and cloning. Nevertheless, CAF has been more and more-precisely defined-it is exclusively produced by CD8+ T cells and its action is dose dependent and major histocompatibility complex (MHC) unrestricted'. Additionally, CAF is active against HIV-I, HIV-Z, and simian immunodeficiency virus (SW), is able to block viral RNA transcription, and lacks identity with any other known cytokines. It has also been shown that the concentration of CAF is inversely correlated with disease progression and that CAF is involved in the phenomenon of resistance to HIV infection in HIV-seroneg-ative individuals exposed to HIV (reviewed in Ref. 2). Furthermore, it was observed

Journal of Clinical Virology, Feb 1, 2008

Background: Previous in vitro studies indicated that Atazanavir (ATV) has a distinct resistance p... more Background: Previous in vitro studies indicated that Atazanavir (ATV) has a distinct resistance profile than other protease inhibitors (PIs). In treatment-experienced patients ATV resistance is characterised by the accumulation of at least four mutations among those that confer cross-resistance to the PIs. Objective: We studied the evolution of PIs resistance mutations in 10 HAART-failed patients undergoing ATV enrolled in an early access program. Study design: Virus genotypic resistance was determined from plasma collected at baseline and during treatment. HIV-RNA was extracted and the pol region amplified and sequenced. Genotypic data were used to determine drug susceptibility. Phylogenetic analysis was performed. Results: At baseline, genotypic data showed cross-resistance patterns to approved PIs in 6 patients. In two of these subjects new mutations (I54V and A71V) conferring cross-resistance emerged after 3 months of therapy. The I50L mutation was evidenced in one subject after 12 months of treatment. The "virtual" phenotype analysis mirrored the resistance profiles to ATV and other PIs and evidenced differences with tipranavir and darunavir. Conclusion: Genotype evolution within the protease region did not emerge at significant levels during salvage therapy of multidrug-experienced patients. ATV exhibited certain/same virologic effect on the majority of our patients.

Journal of Medical Virology, Mar 12, 2018

SARS-CoV-2 is constantly evolving leading to new variants. We analysed data from 4,400 SARS-CoV-2... more SARS-CoV-2 is constantly evolving leading to new variants. We analysed data from 4,400 SARS-CoV-2-positive samples in order to continue variant surveillance in Italy to evaluate their epidemiological and relative impact on public health in the period April-December 2021. The main circulating strain (76.2%) was Delta followed by Alpha (13.3%), Omicron (5.3%) and Gamma variants (2.9%). B.1.1 lineages, Eta, Beta, Iota, Mu and Kappa variants represented around 1% of cases. Overall, 48.2% of subjects were not vaccinated with a lower median age compared to vaccinated subjects (47 vs. 61 years). An increasing number of infections in vaccinated subjects was observed overtime, with the highest proportion in November (85.2%). Variants correlated with clinical status; the largest proportion of symptomatic patients (59.6%) was observed among Delta variant, while subjects harboring Gamma variant showed the highest proportion of asymptomatics (21.6%), albeit also of deaths (5.4%). The Omicron var...

Acta Bio Medica : Atenei Parmensis, 2018

The objective of this revision is - through an analysis of the literature – to highlight the rele... more The objective of this revision is - through an analysis of the literature – to highlight the relevance and importance of drug addiction in the entry of Hepatitis C virus (HCV) and acquired immunodeficiency (HIV) in Italy, with a review of the history of the HCV various strains that have spread over time through this population (especially in relation to genotypes 3, 4 and in part 1), using the most advanced methods related to the phylogeny and geography of the virus. (www.actabiomedica.it)

Virology Journal, 2021

A growing number of emerging SARS-CoV-2 variants is being identified worldwide, potentially impac... more A growing number of emerging SARS-CoV-2 variants is being identified worldwide, potentially impacting the effectiveness of current vaccines. We report the data obtained in several Italian regions involved in the SARS-CoV-2 variant monitoring from the beginning of the epidemic and spanning the period from October 2020 to March 2021.

Pathogens, 2021

There have been previous reports of the human-to-cat transmission of SARS-CoV-2, but there are on... more There have been previous reports of the human-to-cat transmission of SARS-CoV-2, but there are only a few molecular studies that have compared the whole genome of the virus in cats and their owners. We here describe a case of domestic SARS-CoV-2 transmission from a healthcare worker to his cat for which nasopharyngeal swabs of both the cat and its owner were used for full-genome analysis. The results indicate that quarantine measures should be extended to pets living in SARS-CoV-2-infected households.

Infection, Genetics and Evolution, 2019

Zika virus (ZIKV), a vector-borne infectious agent that has continuous diffusion models in making... more Zika virus (ZIKV), a vector-borne infectious agent that has continuous diffusion models in making more reliable phylogeographic reconstructions of emerging viruses. Time-scaled phylogeography of complete Zika virus genomes using discrete and continuous space diffusion models

Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, Jan 28, 2017

Hepatitis B virus (HBV) infection reactivation is associated with high morbidity and mortality in... more Hepatitis B virus (HBV) infection reactivation is associated with high morbidity and mortality in patients with haematological malignancy and/or haematopoietic stem cell transplantation (HSCT) however information on this issue is limited. The scope of this position paper is to provide recommendations on HBV screening, monitoring, prophylaxis, treatment and vaccination in the patients described above. - These recommendations were developed from one meeting of experts attended by different Italian scientific societies as well as from a systematic literature review (through December 31, 2016) on HBV infection in haematological patients and in patients who underwent HSCT published in the same issue of this journal. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to provide a grading of each recommendation's quality. These recommendations provide the answers to the following questions:1. HBV screening and monitoring: Who should be sc...

The new microbiologica, 2015

Thanks to the development of antiretroviral agents to control HIV replication, HIV infection has ... more Thanks to the development of antiretroviral agents to control HIV replication, HIV infection has turned from a fatal disease into a treatable chronic infection. The present work collects the opinions of several experts on the efficacy and safety of recently approved second generation of integrase inhibitors and, in particular, on the role of this new class of drugs in antiretroviral therapy. The availability of new therapeutic options represents an opportunity to ameliorate the efficacy of cART in controlling HIV replication also within viral reservoirs. The personalization of the treatment driven mainly by the management of comorbidities, HIV-HCV co-infections and aging, will be easier with antiretroviral drugs without drug-drug interactions and with a better toxicity and tolerability profile. Future assessment of economic impact for the introduction of new innovative drugs in the field of antiretroviral therapy will likely need some degree of adjustment of the evaluation criteria ...

The new microbiologica, 2012

for the Italian HIV Guidelines Working Group *All members of the Italian HIV Guidelines Working G... more for the Italian HIV Guidelines Working Group *All members of the Italian HIV Guidelines Working Group are listed in the acknowledgment session.

PLoS ONE, 2013

This work aims at identifying a set of humoral immunologic parameters that improve prediction of ... more This work aims at identifying a set of humoral immunologic parameters that improve prediction of the activation process in HIV patients. Starting from the well-known impact of humoral immunity in HIV infection, there is still a lack of knowledge in defining the role of the modulation of functional activity and titers of serum antibodies from early stage of infection to the development of AIDS. We propose an integrated approach that combines humoral and clinical parameters in defining the host immunity, implementing algorithms associated with virus control. A number of humoral parameters were simultaneously evaluated in a whole range of serum samples from HIV-positive patients. This issue has been afforded accounting for estimation problems typically related to ''feasibility'' studies where small sample size in each group and large number of parameters are jointly estimated. We used nonparametric statistical procedures to identify biomarkers in our study which included 42 subjects stratified on five different stages of HIV infection, i.e., Elite Controllers (EC), Long Term Non Progressors (LTNP), HAART, AIDS and Acute Infection (AI). The main goal of the paper is to illustrate a novel profiling method for helping to design a further confirmatory study. A set of seventeen different HIV-specific blood humoral factors were analyzed in all subjects, i.e. IgG and IgA to gp120IIIB, to gp120Bal, to whole gp41, to P1 and T20 gp41 epitopes of the MPER-HR2 region, to QARILAV gp41 epitope of the HR1 region and to CCR5; neutralization activity against five different virus strains and ADCC were also evaluated. Patients were selected on the basis of CD4 cell counts, HIV/RNA and clinical status. The Classification and Regression Trees (CART) approach has been used to uncover specific patterns of humoral parameters in different stages of HIV disease. Virus neutralization of primary virus strains and antibodies to gp41 were required to classify patients, suggesting that clinical profiles strongly rely on functional activity against HIV.

Journal of Clinical Virology, 2008

Journal of Clinical Microbiology, 2001

We studied the human immunodeficiency virus type 1 phenotypic and genotypic profiles of a dual dr... more We studied the human immunodeficiency virus type 1 phenotypic and genotypic profiles of a dual drug-resistant isolate (isolate 14aPost-DR) selected for zidovudine (ZDV) and lamivudine (3TC) resistance and then cultured in the presence of 3TC and a protease inhibitor: indinavir (IDV), ritonavir, or KNI-272. The IDV-treated virus was highly resistant to 3TC, ZDV, and IDV and accumulated protease mutations at positions M46I and V82F. A change from alanine to valine was observed in 4 of 10 clones in the P2 position of the p7-p1 Gag-protease cleavage site, linked to position M46I in the dominant viral quasispecies. Previous 3TC resistance did not impair the development of additional mutations in the protease and Gag-protease cleavage regions.

JAIDS Journal of Acquired Immune Deficiency Syndromes, 2013

Background: The incidence of non-AIDS defining cancers (NADCs) in HIV-positive patients has incre... more Background: The incidence of non-AIDS defining cancers (NADCs) in HIV-positive patients has increased over recent years. Most studies of the risk and spectrum of NADCs are primarily based on male populations and only a few have provided specific information regarding females. Methods: We retrospectively analysed all incident NADCs occurring in a cohort of HIVpositive patients followed up between 1985 and 2011. Incidence rates before and after the introduction of highly active antiretroviral therapy (HAART) were examined using Poisson regression models. Standardised incidence ratios (SIRs) were used to compare the cancer risk of HIV-infected subjects with that of the age-and gender-matched general population as estimated by the Milan Cancer Registry. Results: 5,924 patients (4,382 males and 1,542 females) contributed 50,990 person-years (py) to the follow-up. Among them 144 had new NADC diagnosis. The overall incidence increased from 1.0 case/1,000 py in the pre-HAART period to 4.5 cases/1,000 py in the HAART period (p <0.01). In women, the risks were higher than expected in the case of cancer of the vulva (SIR 69.2), Hodgkin lymphoma (SIR 7.5), anal cancer (SIR 41.2), and lung cancer (SIR 4.8). In men, the risks were higher than expected in the case of anal cancer (SIR 91.5), Hodgkin lymphoma (SIR 13.0), tonsil cancer (SIR 10.9), lung cancer (SIR 2.1), and liver cancer (SIR 7.1). Conclusions: The spectrum and incidence of NADCs in our cohort increased over time. The incidence of NADCs, especially virus-and smoking-associated cancers, was significantly higher than expected in HIV-positive men and women.

Infection, 2009

Background: Individuals with advanced HIV infection naïve to antiretroviral therapy represent a s... more Background: Individuals with advanced HIV infection naïve to antiretroviral therapy represent a special population of patients frequently encountered in clinical practice. They are at high risk of disease progression and death, and their viroimmunologic response following the initiation of highly active antiretroviral therapy may be more incomplete or slower than that of other patients. Infection management in such patients can also be complicated by underlying conditions, comorbidities, and the need for concomitant medications. Aim: To provide practical guidelines to those clinicians providing care to HIV-infected patients in terms of diagnostic assessment, monitoring, and treatment. Conclusions: The principals of antiretroviral treatment in asymptomatic naïve patients with advanced HIV infection are the same as those applicable to the general population with asymptomatic HIV infection. Naïve patients with advanced HIV infection and a history of AIDS-defining illnesses urgently need antiretroviral treatment, with the choice of antiretroviral regimen and timetable based on such factors as concomitant treatment and prophylaxis, drug interactions, and potential concomitant drug toxicity. Finally, an adequate counseling program-both before and after HIV-testing-that includes aspects other than treatment adherence monitoring is a crucial step in disease management.

Clinical and Experimental Immunology, 2006

SummaryCD81 is a member of the tetraspan superfamily and plays a role in immune responses and in ... more SummaryCD81 is a member of the tetraspan superfamily and plays a role in immune responses and in hepatitis C virus (HCV) pathogenesis. We analysed CD81 cell surface and mRNA expression in different lymphocytic subpopulations in human immunodeficiency virus (HIV)-1, HCV and dually infected subjects. CD81 cell surface expression was evaluated with fluorescence activated cell sorter (FACS) analysis; mRNA quantification was performed with semiquantitative polymerase chain reaction (PCR). CD81 cell surface expression on CD4+ T lymphocytes was significantly different by analysis of variance (anova) test (P < 0·001), with reduced expression in HIV-1+ patients. In B lymphocytes, higher cell surface expression was present in HIV-1, in HCV and in dually infected subjects compared to healthy controls. CD81 expression on B lymphocytes showed a positive correlation with plasma HIV-RNA. CD81 mRNA levels in B lymphocytes were significantly higher in HIV-1+ patients compared to healthy controls....

Infection, 1982

Mixed polyclonal cryoglobulinaemia was evidenced in a 49-year-old woman admitted to our hospital ... more Mixed polyclonal cryoglobulinaemia was evidenced in a 49-year-old woman admitted to our hospital because of Proteus mirabilis sepsis associated with polyarthralgia and purpuric manifestations on the lower limbs. Cryoglobulins and circulating immune complexes decreased during the second week of illness and disappeared after recovery. CH50, C3 and properdin factor B, which were low during the early phase of the illness, returned to normal; C4 was normal throughout. The rapid clearance of cryoglobulins and immune complexes and the restoration of a normal complement profile might all be explained by the gradual elimination of P. mirabilis due to chemotherapeutic treatment.

Scientific Reports

The aims of this study were to characterize new SARS-CoV-2 genomes sampled all over Italy and to ... more The aims of this study were to characterize new SARS-CoV-2 genomes sampled all over Italy and to reconstruct the origin and the evolutionary dynamics in Italy and Europe between February and June 2020. The cluster analysis showed only small clusters including < 80 Italian isolates, while most of the Italian strains were intermixed in the whole tree. Pure Italian clusters were observed mainly after the lockdown and distancing measures were adopted. Lineage B and B.1 spread between late January and early February 2020, from China to Veneto and Lombardy, respectively. Lineage B.1.1 (20B) most probably evolved within Italy and spread from central to south Italian regions, and to European countries. The lineage B.1.1.1 (20D) developed most probably in other European countries entering Italy only in the second half of March and remained localized in Piedmont until June 2020. In conclusion, within the limitations of phylogeographical reconstruction, the estimated ancestral scenario sugg...

Newly characterising 245 Italian and Albanian HCV-2 NS5B sequences collected between 2001 and 201... more Newly characterising 245 Italian and Albanian HCV-2 NS5B sequences collected between 2001 and 2016 was used to reconstruct the origin and dispersion pathways of HCV-2c. The tree of a subset of these sequences aligned with 247 publicly available sequences was reconstructed in spatio-temporal scale using the Bayesian approach, and the effective replication number (Re) was estimated using the birth-death model. Our findings show that HCV-2c was the most prevalent subtype in Italy and Albania, and that GT2 originated in Guinea Bissau in the XVI century and spread to Europe in the XX century. The HCV-2c subtype had two internal nodes respectively dating back to the 1930s and 1950s having as most probable locations Ghana and Italy, respectively. Phylodynamic analysis revealed an exponential increase in the effective number of infections and Re in both Italy between the 1950s and 1980s, and Albania between the 1990s and the early 2000s. It seems very likely that HCV-2c reached Italy from A...