Publications by authors named "Adriano Lazzarin"

319 Publications

Residual viremia in HIV-infected patients who continue a 2-drug or switch to a 3-drug integrase strand transfer inhibitor-based regimen.

AIDS 2021 Apr 6. Epub 2021 Apr 6.

Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milano, Italy Vita-Salute San Raffaele University, Milano, Italy.

In this randomized, single-center, open-label, 96-week, superiority, controlled trial of 50 HIV-infected patients with HIV-RNA <50 copies/mL on a two-drug regimen based on dolutegravir plus one reverse transcriptase inhibitor, switching to a single tablet regimen of cobicistat, elvitregravir, emtricitabine plus tenofovir alafenamide did not appear to mitigate the burden of residual viremia, both at week 48 and at week 96. The immunological changes observed during follow-up and the safety of the two regimens were similar.
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http://dx.doi.org/10.1097/QAD.0000000000002908DOI Listing
April 2021

Exercise ECG for coronary artery disease screening in people living with HIV.

AIDS 2021 05;35(6):933-938

Faculty of Medicine and Surgery, Vita-Salute San Raffaele University.

Background: Coronary artery disease (CAD) is one of the leading causes of death among people living with HIV (PLWH). We evaluated ECG stress testing (EST) for detecting CAD in PLWH with multiple cardiovascular risk factors.

Methods: CORDIS was a cross-sectional study conducted in PLWH. Inclusion criteria were men at least 50 years or postmenopausal women, HIV-1 RNA less than 50 copies/ml and at least one of the following cardiovascular risk factor: familial history of CAD, smoking, hypertension, hypercholesterolemia or diabetes. Patients with a previous diagnosis of CAD or with cardiac symptoms were excluded. EST was performed concomitantly with bilateral carotid color-Doppler ultrasonography (CDU) and evaluated by a cardiologist. Results were described by median (interquartile range) or frequency (%). Logistic regression was applied to evaluate predictive factors of inducible myocardial ischemia (IMI).

Results: EST and CDU were performed in 309 individuals; IMI prevalence was 7.4% [95% confidence interval (CI): 5.0-11.0%]. Among patients with a normal CDU, no cases of IMI were observed. In people with abnormal CDU, IMI prevalence increased accordingly with the atherosclerotic cardiovascular disease (ASCVD) risk score: 10.2%, 16.9%, 19.7%, 27.8% and 30.4% among individuals with ASCVD score 7.5% or less, more than 7.5%, more than 10%, more than 15% and more than 20%, respectively (P for trend: 0.02). At multivariate analysis, ASCVD risk score was associated with EST suggestive of IMI (adjusted odds ratio for 1% increase = 1.08; 95% CI: 1.02-1.13, P = 0.005) and with confirmed IMI (adjusted odds ratio for 1% increase = 1.11; 95% CI: 1.04-1.19, P = 0.003).

Conclusion: Prevalence of IMI was 7.4% in the CORDIS study. We suggest EST as first-line screening for CAD in PLWH without cardiac symptoms, with an abnormal CDU and a high ASCVD risk score.
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http://dx.doi.org/10.1097/QAD.0000000000002828DOI Listing
May 2021

Secondary infections in patients hospitalized with COVID-19: incidence and predictive factors.

Clin Microbiol Infect 2021 Mar 24;27(3):451-457. Epub 2020 Oct 24.

Unit of Infectious and Tropical Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.

Objectives: The aim of our study was to describe the incidence and predictive factors of secondary infections in patients with coronavirus disease 2019 (COVID-19).

Methods: This was a cohort study of patients hospitalized with COVID-19 at IRCCS San Raffaele Hospital between 25th February and 6th April 2020 (NCT04318366). We considered secondary bloodstream infections (BSIs) or possible lower respiratory tract infections (pLRTIs) occurring 48 hours after hospital admission until death or discharge. We calculated multivariable Fine-Gray models to assess factors associated with risk of secondary infections.

Results: Among 731 patients, a secondary infection was diagnosed in 68 patients (9.3%); 58/731 patients (7.9%) had at least one BSI and 22/731 patients (3.0%) at least one pLRTI. The overall 28-day cumulative incidence was 16.4% (95%CI 12.4-21.0%). Most of the BSIs were due to Gram-positive pathogens (76/106 isolates, 71.7%), specifically coagulase-negative staphylococci (53/76, 69.7%), while among Gram-negatives (23/106, 21.7%) Acinetobacter baumanii (7/23, 30.4%) and Escherichia coli (5/23, 21.7%) predominated. pLRTIs were caused mainly by Gram-negative pathogens (14/26, 53.8%). Eleven patients were diagnosed with putative invasive aspergillosis. At multivariable analysis, factors associated with secondary infections were low baseline lymphocyte count (≤0.7 versus >0.7 per 10/L, subdistribution hazard ratios (sdHRs) 1.93, 95%CI 1.11-3.35), baseline PaO/FiO (per 100 points lower: sdHRs 1.56, 95%CI 1.21-2.04), and intensive-care unit (ICU) admission in the first 48 hours (sdHR 2.51, 95%CI 1.04-6.05).

Conclusions: Patients hospitalized with COVID-19 had a high incidence of secondary infections. At multivariable analysis, early need for ICU, respiratory failure, and severe lymphopenia were identified as risk factors for secondary infections.
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http://dx.doi.org/10.1016/j.cmi.2020.10.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7584496PMC
March 2021

SARS-CoV-2 IgG/IgM Rapid Test as a Diagnostic Tool in Hospitalized Patients and Healthcare Workers, at a large Teaching Hospital in northern Italy, during the 2020 COVID-19 Pandemic.

New Microbiol 2020 Oct 31;43(4):161-165. Epub 2020 Oct 31.

Clinic of Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy.

We describe the outcome of a Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) IgG/IgM rapid test, and discuss the potential suitability of antibody testing. Retrospective single cohort study on patients with suspected Coronavirus Disease 2019 (COVID-19) and asymptomatic Healthcare Workers, enrolled from March to April 2020. Subjects had quantitative PCR (qPCR) test for detection of SARS-CoV-2 via nasal swab and serological testing using the COVID-19 IgG/ IgM Rapid Test (PRIMA Lab SA) immunochromatographic assay. Some subjects underwent chemiluminescence immunoassay (CLIA) after rapid test. The aim of the study was to analyse the proportion of those who developed a positive IgM/IgG response for SARS-CoV-2. The correspondence between the results from rapid testing and CLIA, when available, was evaluated. 97 subjects underwent qPCR for SARS-CoV-2 through nasal swab, which resulted positive in 40/43 (93.0%) of symptomatic patients, 2/40 (5%) of asymptomatic HCW, in no subjects with suspected COVID- 19 (clinical and radiological findings) then excluded by repeated nasal swabs and alternative diagnosis (COVID-19-negative patients, CNPs), and in 6/6 (100%) of patients with confirmed diagnosis and negative follow-up nasal swabs (COVID-19-recovered patients, CRPs). IgM resulted positive in 8/43 (18.6%) of symptomatic patients and in 1/6 (16.7%) of CRPs. IgG resulted positive in 36/43 (83.7%) of symptomatic patients, 2/40 (5%) of HCW, and in 1/8 (12.5%) and 6/6 (100%) of CNPs and CRPs, respectively. A comparison between an IgG/IgM Rapid Test and a following CLIA test showed consistency in negative results in 25/28 of HCW and 8/8 of CNPs tested. Our preliminary data support the role of IgG/IgM Rapid Test (PRIMA Lab SA) immunochromatographic assay as a point-of-care test that may complement molecular tests in the screening of SARS-CoV-2 carriers. The test may gain particular relevance in shortening the time needed to refer patients to a COVID or non-COVID Hospital area and to achieve diagnosis in patients with persistently negative nasal swabs.
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October 2020

Biobanking for COVID-19 research.

Panminerva Med 2020 Oct 19. Epub 2020 Oct 19.

Vita-Salute San Raffaele University, Milan, Italy.

Background: Biobanks are imperative infrastructures, particularly during outbreaks, when there is an obligation to acquire and share knowledge as quick as possible to allow for implementation of science-based preventive, diagnostic, prognostic and therapeutic strategies.

Methods: We established a COVID-19 biobank with the aim of collecting high-quality and well-annotated human biospecimens, in the effort to understand the pathogenic mechanisms underlying COVID-19 and identify therapeutic targets (COVID-BioB, NCT04318366). Here we describe our experience and briefly review the characteristics of the biobanks for COVID-19 that have been so far established.

Results: A total of 46,677 samples have been collected from 913 participants (63.3% males, median [IQR] age 62.2 [51.2 - 74.0] years) since the beginning of the program. Most patients (66.9%) had been admitted to hospital for COVID-19, with a median length of stay of 15.0 (9.0 - 27.0) days. A minority of patients (13.3% of the total) had been admitted for other reasons and subsequently tested positive for SARS-CoV-2. The remainder were managed at home after being seen at the Emergency Department.

Conclusions: Having a solid research infrastructure already in place, along with flexibility and adaptability to new requirements, allowed for the quick building of a COVID-19 biobank that will help expand and share the knowledge of SARS-CoV-2.
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http://dx.doi.org/10.23736/S0031-0808.20.04168-3DOI Listing
October 2020

Relapse of Symptomatic Cerebrospinal Fluid HIV Escape.

Curr HIV/AIDS Rep 2020 10;17(5):522-528

Department of Infectious Diseases, San Raffaele Scientific Institute and San Raffaele Vita-Salute University, Via Stamira d'Ancona 20, 20127, Milan, Italy.

Purpose Of Review: Symptomatic cerebrospinal fluid (CSF) HIV escape defines the presence of neurological disease in combination antiretroviral therapy (cART)-treated persons due to HIV replication in CSF despite systemic suppression or to higher viral replication in CSF than in plasma. The aim was to search for cases of recurrent symptomatic CSF escape and to define their characteristics.

Recent Findings: By review of the literature, we identified symptomatic CSF escape relapses in three patients who had shown clinical remission of a first escape episode following cART optimization. By examination of our cohort of 21 patients with symptomatic CSF escape, we identified five additional patients. In the latter, viral escape relapsed over a median follow-up of 108 months because of low adherence or upon treatment simplification of a previously optimized regimen. cART reoptimization based on resistance profile and potential drug neuropenetration and efficacy led to relapse resolution with no further episodes after a median follow-up of 50 months from relapse. The observation that CSF escape may relapse highlights the importance of long-term neuro-suppressive regimens after a first episode and supports the role of the brain as a reservoir for HIV.
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http://dx.doi.org/10.1007/s11904-020-00526-xDOI Listing
October 2020

Early predictors of clinical outcomes of COVID-19 outbreak in Milan, Italy.

Clin Immunol 2020 08 12;217:108509. Epub 2020 Jun 12.

Vita-Salute San Raffaele University, Milan, Italy; IRCCS San Raffaele Scientific Institute, Milan, Italy.

Background: National health-system hospitals of Lombardy faced a heavy burden of admissions for acute respiratory distress syndromes associated with coronavirus disease (COVID-19). Data on patients of European origin affected by COVID-19 are limited.

Methods: All consecutive patients aged ≥18 years, coming from North-East of Milan's province and admitted at San Raffaele Hospital with COVID-19, between February 25th and March 24th, were reported, all patients were followed for at least one month. Clinical and radiological features at admission and predictors of clinical outcomes were evaluated.

Results: Of the 500 patients admitted to the Emergency Unit, 410 patients were hospitalized and analyzed: median age was 65 (IQR 56-75) years, and the majority of patients were males (72.9%). Median (IQR) days from COVID-19 symptoms onset was 8 (5-11) days. At hospital admission, fever (≥ 37.5 °C) was present in 67.5% of patients. Median oxygen saturation (SpO2) was 93% (range 60-99), with median PaO/FiO ratio, 267 (IQR 184-314). Median Radiographic Assessment of Lung Edema (RALE) score was 9 (IQR 4-16). More than half of the patients (56.3%) had comorbidities, with hypertension, coronary heart disease, diabetes and chronic kidney failure being the most common. The probability of overall survival at day 28 was 66%. Multivariable analysis showed older age, coronary artery disease, cancer, low lymphocyte count and high RALE score as factors independently associated with an increased risk of mortality.

Conclusion: In a large cohort of COVID-19 patients of European origin, main risk factors for mortality were older age, comorbidities, low lymphocyte count and high RALE.
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http://dx.doi.org/10.1016/j.clim.2020.108509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289745PMC
August 2020

HIV-1 recombinant forms in immigrants regularly residing in Milan, northern Italy.

Infection 2020 Aug 19;48(4):553-558. Epub 2020 May 19.

Laboratory Clinical Science, Campus Bio-Medico University, Rome, Italy.

To assess the HIV -1subtypes distribution in HIV-1 positive migrants living in Milan we studied 77 HIV-1 patients followed at the San Raffaele Hospital of Milan. Twenty subjects were born in Europe, 43 in the Americas, 10 in Africa and 4 in Asia. Unsafe heterosexual activity prevailed in migrants born in Africa and male homosexuality in those born in European, American and Asian countries (p = 0.05). The phylogeny showed that 38/77 (49.3%) subjects carried HIV-B subtype while the remaining strains were classified as not pure HIV-1 B subtypes 13/77 (16.9%) or recombinant forms 26/77 (33.8%). Female gender more frequently showed HIV-1 non-B strains and rarely HIV-1 B subtypes (12/39, 30.8% vs. 3/38, 7.9%, p = 0.02). Transmitted drug resistance was identified in 10/77 (13%) patients predominately with B subtype. Our data underscore a large heterogeneity in HIV-1 subtypes and a large proportion of recombinant forms.
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http://dx.doi.org/10.1007/s15010-020-01434-3DOI Listing
August 2020

Dynamics of HIV-1 POL antibodies after ART in chronic HIV-1 infection.

New Microbiol 2020 Apr 19;43(2):55-57. Epub 2020 Apr 19.

IRCCS San Raffaele Scientific Institute, Infectious Diseases, Milan, Italy.

The aim of this retrospective study was to evaluate Western Blot (WB) antibody response against HIV-1 Pol proteins in people on ≥12 months of Antiretroviral Therapy (ART) and factors associated with a negative HIV-1 Pol response or with its seroreversion from positive to negative. Multivariate logistic regression models were performed to assess factors associated with a negative HIV-1 Pol or with HIV-1 Pol seroreversion. A negative HIV-1 Pol was found in 88 (16.6%) of the 530 individuals evaluated. At multivariate analysis, a negative Pol result was associated with an early ART start [adjusted odds ratio (AOR) per 3-months longer = 0.95, 95% CI=0.90-0.99] and a greater CD4+ recovery since ART start [AOR per 100-cells/μL/year higher=1.11, 95%CI=1.01-1.24]. In a subgroup of 140 patients with WB analysis performed both at HIV-1 diagnosis and after a median of 69 months, Pol seroreverted from positive to negative in 22 (15.7%) patients and was associated with a greater CD4+ recovery [AOR per 100-cells/μL/year higher =2.50 (95%CI=1.28-4.87)]. In conclusion, a negative HIV-1 Pol and a seroreversion from positive to negative were observed in more than 15% of subjects included and were associated with a better immunological profile, suggesting a lower viral exposure to the immune system over time.
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April 2020

Molecular epidemiology of HIV-1 infection in immigrant population in northern Italy.

Epidemiol Infect 2020 02 5;148:e19. Epub 2020 Feb 5.

Department of Mental Health and Public Medicine, Campania University Luigi Vanvitelli, Naples, Italy.

Human immunodeficiency virus-1 (HIV-1) is characterised by a vast genetic diversity classified into distinct phylogenetic strains and recombinant forms. We describe the HIV-1 molecular epidemiology and evolution of 129 consecutive HIV-1 positive migrants living in Milan (northern Italy). Polymerase gene sequences of 116 HIV-1 subtype-B positive patients were aligned with HIV-1 reference sequences (https://www.ncbi.nlm.nih.gov/) by using MAFFT alignment and edited by using Bioedit software. A maximum likelihood (ML) phylogenetic tree was performed by MEGA7 and was visualised by using FigTree v1.4.3. Of 129 migrants, 35 were born in Europe (28 in Eastern Europe), 70 in the Americas (67 in South America), 15 in Africa and nine in Asia; 76.4% were men who have sex with men (MSM). The serotype HIV-1-B prevailed (89.9%), followed by -C, -F1, -D and -A. Compared with 116 HIV-B patients, the 13 with HIV-non-B showed lower Nadir of CD4+ cell/mmc (P = 0.043), more frequently had sub Saharan origin (38.5 vs. 1.72%, P = 0.0001) and less frequently were MSM (40 vs. 74.5%, P = 0.02). The ML phylogenetic tree of the 116 HIV-1 subtype-B positive patients showed 13 statistically supported nodes (bootstrap > 70%). Most of the sequences included in these nodes have been isolated from male patients from the Americas and the most common risk factor was MSM. The low number of HIV-1 non-B subtype patients did not allow to perform this analysis. These results suggest a shift of HIV-1 prevention projects' focus and a continuous monitoring of HIV-1 molecular epidemiology among entry populations. Prevention efforts based on HIV molecular epidemiology may improve public health surveillance setting.
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http://dx.doi.org/10.1017/S0950268819002012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019499PMC
February 2020

Retrospective study on the outcome of two-drug regimens based on dolutegravir plus one reverse transcriptase inhibitor in virologically-suppressed HIV-infected patients.

Int J Antimicrob Agents 2020 Mar 9;55(3):105893. Epub 2020 Jan 9.

Infectious Diseases, IRCCS San Raffaele Scientific Institute, Via Stamira d'Ancona 20, 20127 Milan, Italy. Electronic address:

This was a retrospective study on the efficacy and drug resistance mutations selected at virological failure (VF) in prospectively-followed HIV-infected patients switched to dolutegravir plus rilpivirine (DTG+RPV) or lamivudine (DTG+3TC) while virologically suppressed (HIV-RNA <50 copies/mL). VF was defined as HIV-RNA >50 copies/mL in two consecutive determinations or in a single determination if followed by treatment modification, or >1000 copies/mL in a single determination. Totally, 374 patients were analysed (307 switched to DTG+3TC and 67 to DTG+RPV); 220 had documented historical resistance. The median (IQR) time with HIV-RNA <50 copies/mL before switch was 4.52 (1.93-8.14) years. VF occurred in 17 patients after a median of 1.74 (0.90-2.46) years of follow-up in the 3TC group [incidence rate (95% CI) 3.34 (2.08-5.37) per 100-PYFU] and in 2 patients after a median of 1.78 (1.10-2.99) years of follow-up in the RPV group [incidence rate (95% CI) 1.57 (0.4-6.28) per 100-PYFU]. The 48-week estimated probabilities to maintain virological suppression during treatment with a two-drug regimen were 97.8% (95% CI 95.1-99.0%) vs. 98.3% (95% CI 88.6-99.8%) in the 3TC versus RPV group (P = 0.311). At switch, patients with VF had undetectable HIV-RNA since 0.71 (0.23-1.07) years versus 1.49 (0.64-2.2) years in those without VF (P = 0.001). In the 3TC group, VF was not associated with the presence of historical resistance to nucleoside analogues, and DTG-resistant variants were not selected at VF. One VF to DTG+RPV occurred because of historical resistance to RPV, accompanied by newly selected G140A and Q148R mutations. VF was infrequent with these regimens and was negatively associated with duration of viral undetectability. Drug resistance mutations selected at failure of these regimens were those expected in case of failure of any regimen including DTG, 3TC or RPV, but the impact of resistance to NRTIs on efficacy of DTG+3TC seems lower than expected.
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http://dx.doi.org/10.1016/j.ijantimicag.2020.105893DOI Listing
March 2020

A Mobile Application for Exercise Intervention in People Living with HIV.

Med Sci Sports Exerc 2020 02;52(2):425-433

Infectious Diseases Unit, IRCCS, San Raffaele Scientific Institute, Milano, ITALY.

Purpose: This study aimed to assess 16-wk improvements of physical fitness, metabolic, and psychological parameters in people living with HIV (PLWH) exercising with the support of a smartphone application, as compared with a control group exercising without application.

Methods: This was a randomized, open-label, pilot study enrolling PLWH in a 16-wk protocol consisting of moderate physical activity three times per week, which included an initial coach-supervised period of 4 wk, followed by 12 wk where participants trained independently. Participants were allocated to either an experimental group that trained using a smartphone application (APP) or a control group that practiced following a hard copy training program (No-APP). At baseline (BL) and after 16 wk (W16), patients were assessed for cardiorespiratory fitness, body composition, blood lipid profile, and POMS.

Results: Forty-eight PLWH were screened and 38 were eligible: 20 were allocated to the APP group and 18 to the No-APP group. Two APP and two No-APP participants were lost to follow-up. Intention-to-treat analysis showed a W16 improvement from BL of ≥15% V˙ O2peak in 13 (72%) of 18 in APP, but only in 3 (19%) of 16 in No-APP participants (P = 0.025). Significant W16 improvements were observed in APP, but not in No-APP participants, in V˙O2peak; fat mass and fat-free mass percent; total cholesterol, LDL cholesterol, and triglycerides; vigor; and total mood by POMS. Accordingly, significant percent change differences between the APP and the No-APP groups were observed in V˙O2peak; fat and fat-free mass percent; total cholesterol, LDL cholesterol, and triglycerides; and depression, vigor, anger, and total mood by POMS.

Conclusions: Exercising using a smartphone application improved cardiorespiratory fitness, body composition, cholesterol profiles, and psychological outcomes in PLWH.
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http://dx.doi.org/10.1249/MSS.0000000000002125DOI Listing
February 2020

Viro-immunological outcomes after 13-valent pneumococcal vaccination in HIV-1-infected individuals on stable virological suppression.

AIDS 2019 11;33(13):1987-1994

aDepartment of Infectious Diseases, University Hospital Policlinico, Bari bDepartment of Infectious Diseases, San Raffaele Scientific Institute cDepartment of Infectious Diseases, Vita-Salute San Raffaele University, Milan, Italy.

Background: Very limited data are available on the immunovirological outcomes after 13-valent pneumococcal conjugate vaccine (PCV13) in antiretroviral therapy (ART)-treated patients. The aim of this study was to assess the immune-virological outcomes in HIV-1-infected ART-treated patients on stable virological suppression who underwent pneumococcal conjugate vaccination.

Methods: Retrospective, cohort study on ART-treated HIV-1-infected individuals, age at least 18 years, with three consecutive determinations of HIV-RNA less than 50 copies/ml before the administration of PCV13 (baseline) at San Raffaele Hospital and with at least two HIV-RNA values after vaccination.

Results: Overall 1197 patients underwent PCV13 vaccination. During 6-month of follow-up (594 person-years of follow-up, PYFU), 12 confirmed virological failure and 35 viral blips were observed; the overall incidence rate of confirmed virological failure was 2.02 (95% confidence interval: 0.88-3.16) per 100-PYFU and the incidence rate of viral blips was 5.89 (95% confidence interval: 3.94-7.84) per 100-PYFU. Median CD4 cell count change from baseline at 6 months was +10 cells/μl (interquartile range -67, +111; P = 0.0002). Median change in CD4/CD8 ratio was +0.02 (interquartile range -0.06, +0.11; P < 0.001).

Conclusion: Viral blips and confirmed virological failures were rarely observed in patients on stable virological suppression in the first 6 months following vaccination with PCV13. In addition, no decrease of CD4 cell count and CD4/CD8 ratio was recorded.
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http://dx.doi.org/10.1097/QAD.0000000000002307DOI Listing
November 2019

Homeostatic model assessment for insulin resistance index trajectories in HIV-infected patients treated with different first-line antiretroviral regimens.

J Med Virol 2019 11 16;91(11):1937-1943. Epub 2019 Jul 16.

Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milano, Italy.

Objective: To describe the trajectories of the homeostatic model assessment for insulin resistance (HOMA-IR) index in a cohort of HIV-1 infected patients during their first-line antiretroviral (ART) regimen.

Methods: Retrospective analysis of naïve patients who started ART from 2007 at the Infectious Diseases Unit of the San Raffaele Hospital, Milan. We included patients treated with two nucleoside reverse transcriptase inhibitors (NRTIs, tenofovir, abacavir, lamivudine or emtricitabine), and one anchor drug (ritonavir-boosted protease inhibitor [PI/r], non-NRTI [NNRTI], or integrase strand transfer inhibitor [InSTI]), and with HOMA-IR assessed both before and after the start of ART. Univariate and multivariate mixed linear models estimated HOMA-IR changes during ART.

Results: Among 618 patients included in the study, 218 received InSTI-, 210 PI/r-, and 190 NNRTI-based regimens. Median follow-up was 27.4 (16.3-41.2) months. Adjusted mean change in HOMA-IR index was significantly higher (P = .041) in patients treated with InSTI-based regimens [0.160 (95% CI: 0.003-0.321) units per year] compared with NNRTI-based regimens [-0.005 (95% CI: -0.184-0.074) units per year]; no difference was observed between patients treated with NNRTI- and PI/r-based regimens or between INSTI-based and PI/r-based regimens.

Conclusion: InSTI-based first-line ARTs were independently associated with greater increases in HOMA-IR index.
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http://dx.doi.org/10.1002/jmv.25541DOI Listing
November 2019

Analytical treatment interruption in chronic HIV-1 infection: time and magnitude of viral rebound in adults with 10 years of undetectable viral load and low HIV-DNA (APACHE study).

J Antimicrob Chemother 2019 07;74(7):2039-2046

Infectious Diseases, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) San Raffaele Scientific Institute, Milan, Italy.

Objectives: Despite the fact that there are individuals who have chronic HIV infection, few studies have investigated ART interruption in this setting. The aim of this study was to evaluate the ability to spontaneously control viral replication during analytical treatment interruption (ATI) in adults with chronic HIV-1 infection, on ART, with suppressed viraemia for >10 years and with a low reservoir.

Patients And Methods: This was a prospective, open-label, single-arm, non-randomized, proof-of-concept study (NCT03198325) of subjects with chronic HIV-1 infection, HIV-RNA <50 copies/mL for ≥10 years, without residual viraemia for ≥5 years, CD4+ >500 cells/mm3, HIV-DNA <100 copies/106 PBMCs and without comorbidities or AIDS-defining diseases. Enrolled patients were strictly monitored. The ART regimen in use at ATI was resumed in the case of confirmed viral rebound (CVR, two consecutive HIV-RNA >50 copies/mL). Results are reported as median (IQR).

Results: Nine patients underwent ATI. All participants experienced CVR [4.84 (IQR: 3.47-6.47) HIV-RNA log10 copies/mL] after ATI at a median time of 21 days (range 14-56) and restarted ART. After ART resumption, all the subjects achieved HIV-RNA <50 copies/mL in a median of 88 days (range 15-197). No serious adverse event occurred; one subject experienced acute retroviral syndrome. No significant correlation between baseline factors and time to viral rebound was observed, while the magnitude of viral rebound was significantly associated with pre-ART HIV-1 RNA (Spearman r = 0.786, P = 0.036), nadir CD4+ (Spearman r = -0.800, P = 0.010), baseline CD4+ (Spearman r = -0.667, P = 0.049) and years with undetectable viral load (Spearman r = -0.717, P = 0.030).

Conclusions: Despite a long period of HIV viral load suppression and a low viral reservoir, early and consistent viral rebound was observed during ATI in all subjects.
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http://dx.doi.org/10.1093/jac/dkz138DOI Listing
July 2019

Point-of-care testing for hepatitis C virus infection at an Italian dental clinic: portrait of the pilot study population.

New Microbiol 2019 Jul 3;42(3):133-138. Epub 2019 Jun 3.

Department of Dentistry IRCCS San Raffaele Scientific Institute, Milan, Italy and Dental School, Vita-Salute University, Milan, Italy.

The dental clinic is an appropriate place to promote the prevention of hepatitis C virus (HCV) infection and fast access for care of HCV-positive subjects with new-generation anti-HCV drugs. This study aimed to determine the socio-demographic profile of subjects screened for HCV virus in a dental clinic to acquire useful information for future campaigns of prevention. An easy, free-of-charge, screen salivary test was offered to patients referred to the dental clinic of San Raffaele Scientific Research Hospital in Milan, Italy for dental procedures. These patients were also asked to complete an anonymous questionnaire on demographics and risk behaviours. A total of 1388 of 2097 (66.19%) questionnaires were evaluable. The demographics of the population responding to this initiative was primarily Italians citizen (96.47%), homogeneous gender distribution (55.55%), age over 50 (609 subjects; 43.88%), with high-level education and stable professional positions. 905 subjects (65.20%) were never tested for HCV before. The test showed positive reactivity in 22 cases (1.05%); of these, 21 subjects were known to be HCV-positive, and the test confirmed their status. One subject was newly diagnosed as HCV-positive. The percentage of subjects who were never tested for HCV infection appears too high (905 subjects, i.e., 65.20%), especially among subjects with high level of education and professions, and among adults over 40 or young people (18-25). The easy screening test in dental clinic can help raise awareness, promote early diagnosis and prevention, and provide a fast link to care for HCV infection.
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July 2019

Incidence and Predictors of Serological Treatment Response in Early and Late Syphilis Among People Living With HIV.

Open Forum Infect Dis 2019 Jan 30;6(1):ofy324. Epub 2018 Nov 30.

Vita-Salute San Raffaele University, Faculty of Medicine and Surgery, Milan, Italy.

Background: Few studies have investigated predictors of serological response to syphilis treatment in people living with HIV (PLWH).

Methods: This was a retrospective, longitudinal study on PLWH who were diagnosed with and treated for syphilis who had an assessable serological response between January 2004 and June 2016. Serological treatment response (TR) was defined as a ≥4-fold decline in rapid plasma reagin (RPR) titers or a reversion to nonreactive (if RPR ≤1:4 at diagnosis) 12 months after treatment for early syphilis and 24 months after treatment for late syphilis. Factors associated with a TR were assessed with multivariate Cox proportional hazard models for recurrent events.

Results: A total of 829 episodes of syphilis (686 early, 143 late) in 564 patients were recorded. TR was observed in 732 (88%) syphilis episodes. The proportion of TR differed between early and late syphilis (89% vs 83%, respectively; = .045). For early syphilis, TR was associated with a higher nadir CD4+ cell count (adjusted hazard ratio [AHR], 1.06; = .029), an RPR titer >1:32 at diagnosis (AHR, 1.26; = .009), secondary syphilis (AHR, 1.29; = .008), and cases of syphilis diagnosed in more recent calendar years (AHR, 1.36; < .0001). In late syphilis, TR was more likely to occur for first infections (AHR, 1.80; = .027), for episodes that occurred in more recent years (AHR, 1.62; = .007), and for RPR titers >1:32 at diagnosis (AHR, 2.04; = .002). TR was not associated with the type of treatment regimen in early and late syphilis.

Conclusions: Higher RPR titers at diagnosis and a diagnosis of syphilis that was made in more recent years were associated with TR in early and late syphilis.
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http://dx.doi.org/10.1093/ofid/ofy324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324658PMC
January 2019

Evidence-based renewal of the Italian guidelines for the use of antiretroviral agents and the diagnostic-clinical management of HIV-1 infected persons.

New Microbiol 2018 10;41(4):247-255

San Raffaele Scientific Institute, Milan, Italy.

The Italian Society for Infectious and Tropical Diseases (SIMIT) in collaboration with the Technical Health Committee (Sections L and M) of the Italian Ministry of Health have supported the renewal of the recommendations for the Italian guidelines for the use of antiretroviral agents and the diagnostic-clinical management of HIV-1 infected persons. This publication summarizes the latest updates to the 2017 version of the Italian Guidelines for the management of HIV-1 infected patients and the use of antiretroviral drugs. New recommendations were released framing the clinical questions the use of antiretrovirals according to the Patient Intervention Comparator Outcome (PICO) methodology and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Diagnostic tools for immunological and virological monitoring, when to start, what to start, optimization and therapeutic failure were updated in order to include the recommendation obtained with these newly developed methods. For a complete review of clinical and therapeutic relevant topics we refer the reader to the extended version of the Guidelines.
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October 2018

Brief Report: Hyperbilirubinemia Is Associated With a Decreased Risk of Carotid Atherosclerosis in HIV-Infected Patients on Virological Suppression.

J Acquir Immune Defic Syndr 2018 12;79(5):617-623

Vita-Salute San Raffaele University, Milan, Italy.

Objective: To investigate the association between total, direct, and indirect bilirubin and the presence of carotid lesions in a large sample of HIV-1-infected patients on virological suppression.

Design: Retrospective study on adult HIV-1-infected patients, with a carotid ultrasound (CUS) examination performed between January 2008 and August 2016, with HIV-RNA <50 copies per milliliter at CUS and without previous cardiovascular events.

Methods: Intima media thickness was measured in 4 segments: carotid common artery and bifurcation on the left and right sides. Carotid lesion was defined as an intima media thickness ≥1.5 mm in ≥1 region at CUS. Patients were classified as: normal if all bilirubin values before CUS were below the upper normal limit and with hyperbilirubinemia if ≥1 bilirubin value above upper normal limit before CUS was recorded. Multivariate logistic regression was used to determine whether hyperbilirubinemia showed association with the presence of ≥1 carotid lesion, after adjusting for confounding factors.

Results: Overall, 903 patients were evaluated, 511 with ≥1 and 392 without carotid lesions. At multivariate analysis, total [adjusted odds ratio (95% confidence interval) 0.57 (0.36 to 0.90), P = 0.016] and indirect hyperbilirubinemia before CUS [adjusted odds ratio (95% confidence interval) 0.62 (0.40 to 0.97), P = 0.036] were associated with a lower risk of carotid lesions in addition to younger age, negative hepatitis C virus antibodies, higher nadir CD4, lower low-density lipoprotein cholesterol, higher high-density lipoprotein cholesterol, lower triglycerides, and no use of statin; no effect of atazanavir treatment on carotid lesions was detected.

Conclusions: In HIV-1-treated patients, total or indirect hyperbilirubinemia was likely associated with the absence of carotid lesions.
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http://dx.doi.org/10.1097/QAI.0000000000001854DOI Listing
December 2018

Time spent with residual viraemia after virological suppression below 50 HIV-RNA copies/mL according to type of first-line antiretroviral regimen.

Int J Antimicrob Agents 2018 Oct 13;52(4):492-499. Epub 2018 Sep 13.

Infectious Diseases, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.

Purpose: To investigate if the regimen used when starting antiretroviral therapy (ART) affects the time spent with residual viraemia (RV) after achieving <50 HIV-RNA copies/mL.

Methods: Retrospective cohort study on patients infected with human immunodeficiency virus (HIV), followed prospectively, who started ART with a boosted protease inhibitor (PI/r)-, a non-nucleoside reverse transcriptase inhibitor (NNRTI)- or an integrase inhibitor (InSTI)-based triple regimen, or a regimen with more than three drugs. RV was defined as any detectable polymerase chain reaction (PCR) signal <50 HIV-RNA copies/mL, as assessed by kinetic PCR or Abbott real-time PCR. The percentage of time spent with RV (%RV) was calculated as the cumulative follow-up time spent with RV on the observed follow-up, and was estimated using a generalized linear model.

Results: Seven hundred and seventy-one patients (33%, 32%, 30% and 5% receiving PI/r-, NNRTI-, InSTI-based triple regimens, or a regimen with more than three drugs, respectively) were included in the analysis. After a median of 2.16 (interquartile range 1.27-3.16) years of follow-up, adjusted means of %RV were 37.9% [95% confidence interval (CI) 30.3-45.4%], 23.9% (95% CI 16-31.8%), 25.3% (95% CI 17.8-32.7%) and 45.5% (95% CI 34.6-56.4%) in the PI/r, NNRTI, InSTI and more than three drugs groups, respectively; %RV was significantly higher in patients who started ART with a regimen with more than three drugs (P=0.030), and was significantly lower in patients who started ART with an NNRTI-based regimen (P<0.0001) or an InSTI-based regimen (P=0.030) than in those who started ART with a PI/r-based regimen. %RV was independently associated with pre-ART HIV-RNA (P<0.0001), time to HIV-RNA <50 copies/mL (P<0.0001), NRTI backbone (P=0.037) and baseline HIV-RNA (P<0.0001).

Conclusion: First-line regimens based on PIs/r or on more than three drugs are associated with a greater percentage of time spent with RV after achieving virological suppression.
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http://dx.doi.org/10.1016/j.ijantimicag.2018.07.001DOI Listing
October 2018

Darunavir for the treatment of HIV infection.

Expert Opin Pharmacother 2018 Jul 18;19(10):1149-1163. Epub 2018 Jun 18.

b Unit of Management and Antiretroviral Treatment of HIV Infection, Division of Immunology, Transplantation and Infectious Diseases , IRCCS San Raffaele Hospital , Milan , Italy.

Introduction: Darunavir (DRV) was the last approved protease inhibitor (PI) and has been extensively used for the treatment of HIV in both naïve and experienced subjects due to its high genetic barrier and efficacy. The introduction in clinical practice of integrase strand transfer inhibitors limited its role in the management of naïve subjects and in antiretroviral treatment simplification strategies. However, recent data from trials that have investigated the new DRV/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) combination showed an excellent efficacy and tolerability of this coformulation both in naïve patients and in those with viral suppression, making D/C/F/TAF a new option for the treatment of HIV infection. Areas covered: The authors present and discuss the efficacy and safety data of DRV when used in antiretroviral-naïve, multiexperienced subjects and in the setting of treatment deintensification in subjects with viral suppression. Moreover, the authors evaluate the recent data from two different Phase III trials on D/C/F/TAF both in treatment-naïve and virologically suppressed subjects. Expert opinion: Although novel antiretroviral drugs may become available over time, DRV continues to represent a valuable option for multiexperienced subjects and has a role in simplification regimens. In addition, the convenience of D/C/F/TAF coformulation may be useful for the future management of HIV-infected subjects.
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http://dx.doi.org/10.1080/14656566.2018.1484901DOI Listing
July 2018

Managing the long surviving HIV patient: a proposal for a multidimensional first-level diagnostic assessment.

New Microbiol 2018 Apr;41(2):112-117

University of Tor Vergata, Rome, Italy.

We propose a multidimensional first-level diagnostic assessment easy to use in routine clinical practice to allow infectious disease specialists to have a general and complete overview of persons living with HIV. Following the Delphi method, articles published from January 1, 2011 on controlled trials, clinical reports and observational studies dealing specifically with HIV and its co-morbidities were selected for review by the authors. Participants in the poll were selected among clinicians and infectious diseases specialists, working in 38 different dedicated HIV centres in Italy. The participants were given access to a website dedicated to the project and received a standardized information package containing a synopsis of the study and a description of the Delphi process and the selected literature. A total of 131 Items were divided into 10 first-level survey areas: anamnesis, objective examination, infectious diseases, osteoporosis diagnosis, metabolic pathologies diagnosis, cardiovascular diagnosis, nephrologic diagnosis, hepatological diagnosis, central nervous system diagnosis, evaluation of quality of life (QoL). This simple and concise first level tool identifies a few areas of multi-organ diagnostic assessment beyond the infectivity area. The identification of these areas will allow us to find shared and validated evaluation procedures with the intent to increase the likelihood of early recognition of patients at risk of comorbidity development, in order to facilitate more effective prevention, thereby reducing the overall impact on the quality of life of patients affected by this chronic illness.
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April 2018

Bictegravir.

Curr Opin HIV AIDS 2018 07;13(4):326-333

Infectious Diseases, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), San Raffaele Hospital, Milan, Italy.

Purpose Of Review: In this review, we will highlight and discuss the recent efficacy and safety data of bictegravir (BIC), a novel second-generation integrase strand transfer inhibitor (INSTI) that has been recently approved, in coformulation with emtricitabine and tenofovir alafenamide (B/F/TAF), for the treatment of HIV-1 infection in antiretroviral naïve subjects and in those with suppressed viremia.

Recent Findings: Preclinical data showed that BIC has a genetic barrier that is higher than that of raltegravir and elvitegravir but is similar to that of dolutegravir (DTG), with retained activity in vitro against isolates containing substitutions associated with resistance against other INSTIs. Its pharmacokinetic interaction risks appear to be low. Results of the phase 3 GS-US-380-1489 and GS-US-380-1490 clinical trials showed that the coformulation B/F/TAF is not inferior to the recommended DTG-containing regimens in naïve subjects. Moreover, B/F/TAF exhibited excellent tolerability, and no treatment-emergent resistance to any component of the coformulation was observed. In addition, preliminary data support switching from DTG and emtricitabine/tenofovir alafenamide or boosted protease inhibitor-containing regimens to B/F/TAF in subjects with undetectable viremia.

Summary: The coformulation bictegravir/emtricitabine/tenofovir alafenamide is set to become a new option in the management of patients who are antiretroviral naïve and in those with suppressed viremia.
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http://dx.doi.org/10.1097/COH.0000000000000468DOI Listing
July 2018

Potential associations between atazanavir exposure and clinical outcome: a pharmacokinetic sub-study from the MODAt randomized trial.

New Microbiol 2018 Apr 2;41(2):106-111. Epub 2018 Mar 2.

Department of Infectious Diseases, San Raffaele Scientific Institute, Milan, Italy.

The 96-week results of the Monotherapy Once a Day with Atazanavir/r (MODAt) study [NCT01511809] showed an inferior virological efficacy of atazanavir (ATV)/ritonavir monotherapy versus triple therapy, which was promptly retrieved by the reintroduction of nucleoside/nucleotide inhibitors of reverse transcriptase [N(n)RTIs]. We aimed to identify potential relationships between ATV exposure and clinical outcome in HIV-1 subjects treated with ATV/ritonavir monotherapy [ATV/r 300/100 mg] versus ATV/ritonavir triple therapy [ATV/r 300/100 mg+2NRTIs]. A chromatographic method coupled with tandem mass spectrometry was applied to analyze ATV plasma concentrations in a pharmacokinetic sub-study from the MODAt trial. Mixed linear models were used to examine the ATV plasma concentration trend during follow-up and to assess the association between ATV plasma concentrations trajectories with the study arm or the occurrence of treatment failure or drugrelated adverse events or the grading of baseline total bilirubin (<3 vs ≥3). The analyses were performed using SAS Software, release 9.4 (SAS Institute, Cary, NC, USA). Overall, ATV plasma Ctrough concentration did not vary during follow-up (slope: +0.75 ng/mL/week, 95%CI: -0.97 to 2.47, p=0.387); trajectories did not differ between study arms (p=0.527). The unadjusted model-based means (95%CI) of ATV Ctrough during follow-up were 835 (95%CI: 657-1012) ng/ml in the ATV/r monotherapy arm as compared to 911 (95%CI: 740-1082) ng/mL in the ATV/r triple therapy arm (p=0.621). Mean ATV Ctrough was similar in subjects with or without adverse events (AEs). Subjects treated with ATV/r monotherapy showed significantly higher ATV concentrations as compared to subjects without adverse events or treated with ATV/r triple therapy. ATV concentrations were associated with the grading of baseline total bilirubin and the occurrence of drug-related AEs but not with HCV infection. Our findings showed a lack of association between ATV concentrations and treatment failure both in ATV/r monotherapy and triple therapy. Conversely, these data emphasized that ATV concentrations are associated with the development of side-effects in both subjects treated with ATV/r monotherapy and subjects treated with ATV/r triple therapy.
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April 2018

Long-term efficacy and safety of rilpivirine plus abacavir and lamivudine in HIV-1 infected patients with undetectable viral load.

PLoS One 2018 16;13(2):e0191300. Epub 2018 Feb 16.

Janssen-Cilag SpA, Medical Affairs, Cologno Monzese-Milan, Italy.

Introduction: A regimen with rilpivirine (RPV), abacavir (ABC) and lamivudine (3TC) is simple and may allow the sparing of tenofovir and protease inhibitors. However, data on use of this combination as a strategy of switch are limited. Aims of the study were to assess the long-term efficacy and safety of this regimen.

Methods: Retrospective study on HIV-1 infected patients followed at the Infectious Disease Department of the San Raffaele Scientific Institute, HBsAg-negative, HLA B5701-negative, with no documented resistance to RPV, ABC and 3TC, with HIV-RNA<50 copies/mL who started RPV plus ABC/3TC from March 2013 to September 2015. The primary outcome was durability [no treatment failure (TF)]. Secondary objectives were to evaluate changes in immunological, metabolic and other safety parameters. TF was defined as the occurrence of virological failure (VF, 2 consecutive values >50 copies/mL) or discontinuation of any drug in the regimen for any reason. Patients' follow-up accrued from the date of RPV plus ABC/3TC initiation to the date of TF (VF or discontinuation of any drug in the regimen) or to the date of last available visit. Time to TF was evaluated by use of the Kaplan-Meier curves. Mixed linear models were applied to evaluate changes in immunological, metabolic and other safety parameters.

Results And Discussion: In this analysis, 100 patients starting RPV plus ABC/3TC were included. By 12, 24 and 36 months after switching to RPV plus ABC/3TC, the proportions of individuals without TF were 88% [95% confidence interval (CI): 79%-93%], 82% (95% CI:73%-89%) and 78% (95% CI:68%-86%), respectively. Time to TF was not significantly influenced by CD4+ nadir (≤200 vs >200 cells/μl; log-rank test: p = 0.311) or pre-ART viral load (<100000 vs ≥100000 copies/mL; log-rank test: p = 0.574) or the type of previous antiretroviral regimen (PI+2NRTIs vs NNRTI+2NRTIs vs Other; log-rank test: p = 0.942). Over a median follow-up of 2.9 years (IQR: 1.9-3.5), 26 subjects discontinued the treatment [10 due to toxicity, 7 for interactions with other drugs, 3 due to cardiovascular risk concern, 2 due to single viral blip, 1 due to VF, 1 for asthma, 1 patient's decision, 1 due to enrolment in a study protocol].

Conclusions: In this retrospective study, long-term use of RPV plus ABC/3TC regimen is effective and safe. Efficacy of this regimen was not found to be affected by low CD4+ nadir or high pre-ART viral load.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0191300PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5815573PMC
March 2018

Diagnostic and Prognostic Value of JC Virus DNA in Plasma in Progressive Multifocal Leukoencephalopathy.

Clin Infect Dis 2018 06;67(1):65-72

Department of Infectious Diseases, San Raffaele Scientific Institute, Milano, Italy.

Background: Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease caused by the polyomavirus JC (John Cunningham; JCV) that affects patients with impaired immune systems. While JCV-DNA detection in cerebrospinal fluid (CSF) is diagnostic of PML, the clinical significance of plasma JCV-DNA is uncertain.

Methods: We retrospectively analyzed plasma samples from PML patients that were drawn close to disease onset and from controls without PML. In PML patients, we compared plasma JCV-DNA detection and levels to clinical and laboratory parameters, and patient survival.

Results: JCV-DNA was detected in plasma of 49/103 (48%) patients with PML (20/24, 83%, human immunodeficiency virus [HIV] negative; 29/79, 37%, HIV-positive) and of 4/144 (3%) controls without PML (0/95 HIV-negative; 4/49, 8%, HIV-positive), yielding a diagnostic sensitivity and specificity of 48% and 97% (83% and 100% in HIV-negative; 37% and 92% in HIV-positive), respectively. Among 16 PML patients with undetectable CSF JCV-DNA, 4 (25%) had detectable plasma JCV-DNA. Plasma JCV-DNA levels were independently associated with CSF levels (P < .0001) and previous corticosteroid treatment (P = .012). Higher plasma JCV-DNA levels were associated with disease progression in HIV-negative patients (P = .005); in HIV-positive patients, there was an increased risk of progression only in those treated with combination antiretroviral therapy (cART; P < .0001).

Conclusions: Testing JCV-DNA in plasma might complement PML diagnosis, especially when CSF is unavailable or JCV-DNA not detectable in CSF. In addition, JCV-DNA plasma levels could be useful as a marker of disease progression in both HIV-negative and cART-treated, HIV-positive PML patients.
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http://dx.doi.org/10.1093/cid/ciy030DOI Listing
June 2018

Recommendations for the management of pulmonary fungal infections in patients with rheumatoid arthritis.

Clin Exp Rheumatol 2017 Nov-Dec;35(6):1018-1028. Epub 2017 Nov 28.

Department of Medical and Biological Sciences, Rheumatology Clinic, Santa Maria della Misericordia University Hospital, Udine, Italy.

Often life-threatening pulmonary fungal infections (PFIs) can occur in patients with rheumatoid arthritis (RA) receiving disease-modifying anti-rheumatic drugs (DMARDs). Most of the data concerning PFIs in RA patients come from case reports and retrospective case series. Of the ve most widely described PFIs, Pneumocystis jirovecii pneumonia (PJP) has rarely been seen outside Japan, pulmonary cryptococcosis has been diagnosed in only a small number of patients worldwide, pulmonary coccidioidomycosis has almost only been observed in endemic areas, the limited number of cases of pulmonary histoplasmosis have mainly occurred in the USA, and the rare cases of invasive pulmonary aspergillosis have only been encountered in leukopenic patients. Many aspects of the prophylaxis, diagnosis and treatment of PFIs in RA patients remain to be defined, as does the role of each DMARD in increasing the risk of infection, and the possibility of resuming biological and non-biological DMARD treatment after the infection has been cured. The recommendations for the management of PFIs described in this paper are the product of a consensus procedure promoted by the Italian group for the Study and Management of Infections in Patients with Rheumatic Diseases (the ISMIR group).
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March 2018

Durability of switch regimens based on rilpivirine or on integrase inhibitors, both in association with tenofovir and emtricitabine, in HIV-infected, virologically suppressed patients.

BMC Infect Dis 2017 11 16;17(1):723. Epub 2017 Nov 16.

Infectious Diseases, San Raffaele Scientific Institute, Via Stamira d'Ancona 20, 20127, Milan, Italy.

Background: Switch strategies based on rilpivirine/tenofovir/emtricitabine or on an integrase inhibitor (InSTI) plus tenofovir/emtricitabine have never been compared in randomized clinical trials. The main aim of the study was to investigate the durability of these two switch regimens in virologically suppressed, HIV-infected patients.

Methods: Retrospective analysis of patients who started rilpivirine or an InSTI (both with tenofovir and emtricitabine) with <50 HIV-RNA copies/mL and had at least one HIV-RNA assessed while receiving the study regimen. Virological failure (VF) was defined as two consecutive measurements of HIV-RNA >50 copies/mL. Treatment failure (TF) was define as either VF or discontinuation of any drug of the regimen. Durability was assessed by the Kaplan-Meier method and compared by Log-rank test. Residual viremia was defined as any detectable HIV-RNA below 50 copies/mL, as assed by a real-time PCR assay.

Results: Six hundred seventy-five patients (466 switched to a rilpivirine-, 209 switched to an InSTI-based regimen [18% dolutegravir, 39% raltegravir, 43% elvitegravir/cobicistat] were included in the analysis. The median (interquartile range, IQR) follow-up in the rilpivirine and in the InSTI group was 16.7 (8.8-22.2) and 10.4 (5.4-19.6) months. The 1-year cumulative probabilities (95%CI) of VF and TF were 0.97% (0.36%-2.62%) and 9.73% (7.21%-13.06%) in the rilpivirine group and 1.83% (0.57%-5.77%) and 8.75% (5.25%-14.4%) in the InSTI group, with no difference between groups (p = 0.328 and 0.209 for VF and TF). The proportion of time spent with residual viremia was comparable in the two groups (9% [IQR 0.5%-49%] and 17% [IQR 0.5%-50%] in the rilpivirine and in the InSTI group, p = 0.087). By the multivariable Cox regression model, TF was independently associated with being on therapy with a protease inhibitor vs. a non-nucleoside reverse transcriptase inhibitor at switch (AHR = 0.52; 95%CI = 0.31-0.90; p = 0.018), baseline total/HDL-cholesterol ratio (AHR = 1.19 per 0.5-units increments; 95%CI = 1.06-1.34; p = 0.004), baseline estimated glomerular filtration rate (AHR = 0.78 per 10-units increments; 95%CI = 0.67-0.90; p = 0.001) and baseline hemoglobin (AHR = 0.78 per 1-unit increments; 95%CI = 0.64-0.94; p = 0.009), but not with treatment group (rilpivirine vs. InSTI).

Conclusions: In our clinical practice, the durability of the two regimens was comparable and both showed a very low probability of VF.
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http://dx.doi.org/10.1186/s12879-017-2831-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5691866PMC
November 2017

Presence of multiple genotypes in subjects with HPV-16 infection is highly associated with anal squamous intraepithelial lesions in HIV-1 infected males.

PLoS One 2017 31;12(10):e0186367. Epub 2017 Oct 31.

Infectious Diseases Department, San Raffaele Scientific Institute, Milan, Italy.

Objectives: The aim of the study was to determine the prevalence of abnormal cytological findings, high risk (HR)-HPV genotypes and to identify factors associated with an abnormal cytological findings in a cohort of HIV-infected males.

Patients And Methods: Retrospective observational study on HIV-infected male patients who performed screening in the absence of clinical symptoms. Cytological abnormalities were classified as atypical squamous cells of undetermined significance (ASC-US), low-grade(LSIL) or high high-grade squamous intraepithelial lesion (HSIL). Logistic regression models were used to identify predictors of having LSIL/HSIL.

Results: Among 875 pts, abnormal cytology findings were observed in 254 (29%, 95% CI: 26.1%-32.1%) subjects: 142 (16%) had LSIL and 49 (6%) HSIL. Overall, 581 (66%, 95%CI: 63.2%-69.5%) subjects had ≥1 HR-HPV type and 269 (31%) had ≥2 HR HPV types. Multivariate logistic regression showed that subjects with multiple HR-HPV genotypes (OR = 1.351, 95%CI: 1.005-2.111) and with HPV-16 type (OR = 2.032, 95%CI: 1.313-3.146) were more likely to have LSIL/HSIL in addition to a lower CD4+/CD8+ ratio, a previous diagnosis of syphilis and a positive viral load. In another multivariate model, the presence of multiple HPV types in subjects with HPV-16 type was associated with the highest adjusted OR of having a LSIL/HSIL (OR = 2.598, 95%CI: 1.460-4.624).

Conclusions: In HIV-infected men, the prevalence of abnormal cytological findings was of 29% and of HR-HPV was 66%. The concomitant presence of HPV-16 and multiple HR genotypes was associated with an increased risk of abnormal cytological findings. These data highlight the importance of screening multiple HPV genotypes in HIV-infected patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0186367PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5663371PMC
November 2017