Factors Associated with Pneumonia in Patients Hospitalized with COVID-19 and the Role of Vaccination.

Patients with COVID-19 can develop different forms of the illness with more or less severe symptoms. A 2-year retrospective cohort study was conducted to evaluate the factors associated with the development of pneumonia in patients hospitalized with COVID-19 from March 2020 to February 2022. A total of 385 patients (59.0% males) with a mean age of 69.0 ± 16.0 years were included. At hospital admission, 318 patients (82.6%) reported one or more comorbidities, namely 201 (52.2%) subjects were affected by hypertension, 98 (25.5%) type 2 diabetes, 84 (21.8%) obesity, 36 (9.4%) cancer, and 14 (3.6%) suffered from kidney disease and were being treated with dialysis, and 76 (19.7%) resulted in being vaccinated with a higher prevalence of BNT162b2 vaccine (15.0%). Pneumonia was diagnosed in 276 (71.7%) patients. Multivariate regression analysis showed that pneumonia in COVID-19 patients was positively associated with type 2 diabetes (OR 1.81; 95% CI 1.00-3.27), obesity (OR 2.52; 95% CI 1.27-4.98), and negatively with hypertension (OR 0.58; 95% CI 0.35-0.96). Vaccination against SARS-CoV-2 resulted in a strongly protective factor against the development of pneumonia in COVID-19 patients (OR 0.49; 95% CI 0.28-0.85).

Clinical characteristics and risk factors associated with COVID-19 mortality in a non-Intensive Care Unit.

Introduction: The Coronavirus disease 2019 caused by a new Coronavirus (SARS-CoV-2) throughout the pandemic period has been characterised by a wide spectrum of clinical manifestations, courses, and outcomes. In particular, most patients with severe or critical symptoms re-quired hospitalization. The demographic and clinical characteristics of patients upon admission to the hospital, as well as pre-existing medical conditions, seem to have affected the clinical out-come. Predictive factors of inauspicious outcome in non-Intensive Care Unit hospitalized patients were investigated. Methods: A retrospective, single-centre, observational study of 239 patients with confirmed COVID-19 disease admitted during the first waves of the pandemic to the Infectious Disease Operative Unit of a hospital in Southern Italy was conducted. Demographic characteristics, under-lying diseases, and clinical, laboratory, and radiological findings were collected from the patient's medical records. Information about in-hospital medications, days of admission, and out-come were also considered. Inferential statistical analysis was performed to evaluate the association between patients' characteristics upon hospital admission and during in-hospital length of stay and death. Results: Mean age was 67.8 ± 15.8 years; 137/239 (57.3%) patients were males, and 176 (73.6%) had at least one comorbidity. More than half of patients (55.3%) suffered from hypertension. The length of stay in hospital was 16.5 ± 9.9 days and mortality rate of 12.55%. In multivariable logistic regression analysis, predictors of mortality of COVID-19 patients included age (OR, 1.09; CI, 1.04-1.15), Chronic Kidney Disease (OR, 4.04; CI, 1.38-11.85), and need of High Flow Oxygen therapy (OR, 18.23; CI, 5.06-65.64). Conclusions: Patients who died in the hospital had shorted length of stay than that of the surviving patients. Older age, pre-existent chronic renal disease and need of supplemental oxygen represented independent predictors of mortality in patients hospitalized in non-Intensive Care Unit with COVID-19. The determination of these factors allows retrospectively a greater understanding of the disease also in comparison with the successive epidemic waves.

Is telomere length in buccal or salivary cells a useful biomarker of exposure to air pollution? A review.

Telomeres are repetitive DNA-protein sequences located at the end of chromosomes and play an essential role in preserving information in our genome by protecting against end-to-end fusion, nucleolytic degradation, breakage, and inappropriate recombination. The telomeres shorten with aging and this process can be affected by oxidative stress and inflammation. Environmental and occupational factors may contribute to telomere length (TL) shortening, as demonstrated by an increasing number of studies. In particular, air pollution was associated with aging-related health outcomes and molecular alterations, such as telomeric shortening. Leukocytes are widely used for TL measurement. However, buccal and salivary cells have more intimate contact with airborne pollutants and are easier to sample. The objective of this review was to identify whether salivary or buccal TL represents a valid marker for evaluating the effects of pollution on health. The reviewed studies investigated the association between TL and occupational exposure (genotoxic substances in mechanical workers, and pesticides in pesticides applicators), residential traffic exposure (NOx, NO2, PM2.5, PM10, and black carbon), and household air pollution (PM2.5 and black carbon from biomass stoves). The studies involved adults and children. Although few studies have yet been carried out, almost all reported a negative association between salivary or buccal TL and exposure to air pollutants stating that it could be a good indicator of occupational or airborne pollution exposure. However, further research is needed to evaluate the effect of acute versus long-term exposure on salivary or buccal TL as well as the role of confounding factors. Moreover, most of the reviewed studies were conducted on healthy adults, so it is important to deeply investigate how TL is associated with all-cause mortality such as cancer, diabetes, cardiovascular disease, and respiratory disease, how it can be affected during childhood, and which changes over time can be associated with diseases' onset in adulthood.

Fatal Listeria monocytogenes septicemia and meningitis complicated by Candida glabrata fungemia: a case report.

Listeria monocytogenes is a Gram-positive bacteria and etiological agent of listeriosis. It has the ability to colonize the intestinal lumen and cross the intestinal, blood-brain, and placental barriers, leading to invasive listeriosis responsible for septicemia and meningitis in subjects at risk such as patients with diabetes mellitus, the elderly, and immunocompromised individuals and, for maternal-neonatal infection in pregnant women. We report a rare case of L. monocytogenes septicemia and meningitis complicated by Candida glabrata fungemia on a patient with a history of type 2 diabetes mellitus, hypothyroidism, hypertension, chronic kidney failure, chronic ischemic vascular encephalopathy, and atrial fibrillation. Although adequate therapy was rapidly started with an initial partial clinical improvement, the patient suddenly experienced clinical worsening concomitantly with Candida septicemia resulting in a fatal outcome. To our knowledge, this is the first described case of an invasive L. monocytogenes infection complicated by Candida sepsis. We hypothesize that concomitant Candida infection may play a significant role in the pathogenesis and virulence of L. monocytogenes.

The Role of ABO Blood Type in Patients with SARS-CoV-2 Infection: A Systematic Review.

The SARS-CoV-2 infection has caused over 422 million contagions and 5.8 million deaths resulting in a global health crisis. Several studies have investigated the risk factors predisposing to the infection and reported that the host susceptibility can be linked to the ABO blood group, but the current evidence is controversial. We systematically searched for articles in EMBASE, PubMed, and Cochrane library published up to 7 May 2021 to explore the association of the ABO blood group with the susceptibility to SARS-CoV-2 infection. All studies in people undergoing SARS-CoV-2 test controls were included. Odds ratios were obtained in each study and then synthesised by using meta-analysis. Overall, 22 articles were selected and more than 1,200,000 individuals of whom 74,563 resulted positive to SARS-CoV-2 and 1,166,717 resulted negative, were included in the meta-analysis. Overall, 487,985 subjects had blood group A, 151,879 had group B, 52,621 had group AB, and 548,795 had group O. Group O was slightly less associated with infection, as compared to the other three blood groups (OR = 0.91, 95% CI = 0.85-0.99, p = 0.02). Conversely, group A was slightly more associated with infection, as compared to the other three groups (OR = 1.06, 95% CI = 1.00-1.13, p = 0.04). This meta-analysis shows associations between blood groups and SARS-CoV-2 infection and supports the hypothesis that blood type O may have a slightly lower risk of infection, whereas blood type A may have a slightly higher risk of infection.

Atrial fibrillation with aberrant ventricular conduction after receiving Bamlanivimab/Etesevimab: a case report.

Coronavirus Disease 2019 (COVID-19) is affecting millions of people globally. Several neutralizing monoclonal antibodies have been developed to limit the progression and complications of the disease. These treatments provide immediate and passive immunity. The combination therapy with Bamlanivimab plus Etesevimab led to a lower incidence of COVID-19-related hospitalization and death and a faster reduction in the SARS-CoV-2 viral load. No or rare cases of cardiovascular side effects are reported. We present the case of a high-risk 79-years-old woman who developed atrial fibrillation with aberrant ventricular conduction after administration of neutralizing monoclonal-antibodies Bamlanivimab plus Etesevimab. The woman with a history of insulin-dependent diabetes and Grade II follicular Non-Hodgkin Lymphoma previously vaccinated with two doses of Pfizer COVID-19 vaccine, presented with malaise, headache, and SARS-CoV-2 nasal swab reverse transcription-polymerase chain reaction tested positive for the infection. She received a single dose of Bamlanivimab (70 mg) + Etesevimab (1400 mg). After about a week, she developed atrial fibrillation with uncontrolled response to frequent premature ventricular complexes and aberrant ventricular conduction. This case presents a high-risk woman with SARS-CoV-2 infection who developed a serious adverse cardiovascular event some days after receiving neutralizing monoclonal antibodies. Risk factors including sex, age, anxiety related to isolation and infection, and COVID-19 itself may have all contributed to atrial fibrillation. Arrhythmia may rarely occur after monoclonal-antibodies treatment, although recommended timing to monitor patients is from 1 to 24 h after the administration of these antibodies. Appreciation of this potential association is important for evaluating monoclonal-antibody treatments' safety and optimizing patient monitoring and follow-up.

Knowledge, Information Needs and Risk Perception about HIV and Sexually Transmitted Diseases after an Education Intervention on Italian High School and University Students.

Sexually transmitted diseases (STDs) among adolescents and young people represent a significant public health problem that generates a pressing requirement of effective evidence-based education to promote primary and secondary prevention. The objective of the study is to evaluate how knowledge, information needs, and risk perception about HIV and STDs can change after targeted education interventions for students. A total of 436 subjects aged 15-24 attending high school (134 biomedical and 96 non-biomedical fields) and university courses (104 scientific and 102 non-scientific disciplines) were enrolled to respond to a questionnaire before and after the intervention. An improvement in knowledge was found in all groups, with statistically significant knowledge score differences between the four groups in 60% of the items. More than 94% of the students consider it useful to promote information on these issues. Receiving this information generated awareness and safety in more than 85% of high-school students and 93% of University students. Students widely perceived a great risk being infected with HIV/STDs, although pregnancy was seen as a more hazardous consequence of unprotected sex. This study shows that educational interventions are effective in improving knowledge, apart from findings about key knowledge topics, information needs, and risk perception, which provide significant insights to design future targeted education programs.

Liver fibrosis is associated with cognitive impairment in people living with HIV.

PURPOSE: Our aim was to better explore the association between liver fibrosis (LF) and neurocognitive impairment (NCI) in people living with HIV (PLWH). METHODS: We performed a cross-sectional cohort study by consecutively enrolling PLWH at two clinical centers. All subjects underwent a comprehensive neuropsychological battery; NCI was defined as having a pathological performance (1.5 SD below the normative mean) on at least two cognitive domains. LF was explored using FIB4 index; in a subgroup of PLWH, LF was also assessed by transient elastography. RESULTS: A total of 386 subjects were enrolled, of whom 17 (4.4%) had FIB4 > 3.25. In the subgroup of PLWH (N = 127) performing also liver transient elastography, 14 (11%) had liver stiffness > 14 kPa. Overall, 47 subjects (12%) were diagnosed with NCI. At multivariate regression analyses, participants with FIB4 > 1.45 showed a higher risk of NCI in comparison with those with lower values (aOR 3.04, p = 0.044), after adjusting for education (aOR 0.71, p < 0.001), past AIDS-defining events (aOR 2.91, p = 0.014), CD4 cell count, past injecting drug use (IDU), HIV-RNA < 50 copies/mL, and HCV co-infection. Also a liver stiffness > 14 kPa showed an independent association with a higher risk of NCI (aOR 10.13, p = 0.041). Analyzing any single cognitive domain, a higher risk of abnormal psychomotor speed was associated with a liver stiffness > 14 kPa (aOR 223.17, p = 0.019) after adjusting for education (aOR 0.57, p = 0.018), HIV-RNA < 50 copies/mL (aOR 0.01, p = 0.007), age, past IDU, and HCV co-infection. CONCLUSIONS: In PLWH, increased LF, estimated through non-invasive methods, was associated to a higher risk of NCI independently from HCV status.

Atazanavir/ritonavir with lamivudine as maintenance therapy in virologically suppressed HIV-infected patients: 96 week outcomes of a randomized trial.

Objectives: To investigate the long-term safety and efficacy of a treatment switch to dual ART with atazanavir/ritonavir + lamivudine versus continuing a standard regimen with atazanavir/ritonavir + 2NRTI in virologically suppressed patients. Methods: ATLAS-M is a 96 week open-label, randomized, non-inferiority (margin -12%) trial enrolling HIV-infected adults on atazanavir/ritonavir + 2NRTI, with stable HIV-RNA <50 copies/mL and CD4 counts >200 cells/mm3. At baseline, patients were randomized 1:1 to switch to atazanavir/ritonavir + lamivudine or to continue the previous regimen. Here, we report the 96 week efficacy and safety data. The study was registered with ClinicalTrials.gov, number NCT01599364. Results: Overall, 266 subjects were enrolled (133 in each arm). At 96 weeks, in the ITT population, patients free of treatment failure totalled 103 (77.4%) with atazanavir/ritonavir + lamivudine and 87 (65.4%) with triple therapy (difference +12.0%, 95% CI +1.2/+22.8, P = 0.030), demonstrating the superiority of dual therapy. Two (1.5%) and 9 (6.8%) virological failures occurred in the dual-therapy arm and the triple-therapy arm, respectively, without development of resistance to any study drug. Clinical adverse events occurred at similar rates in both arms. A higher frequency of grade 3-4 hyperbilirubinemia (66.9% versus 50.4%, P = 0.006) and hypertriglyceridaemia (6.8% versus 1.5%, P = 0.031) occurred with dual therapy, although this never led to treatment discontinuation. A significant improvement in renal function and lumbar spine bone mineral density occurred in the dual-therapy arm. The evolution of CD4, HIV-DNA levels and neurocognitive performance was similar in both arms. Conclusions: In this randomized study, a treatment switch to atazanavir/ritonavir + lamivudine was superior over the continuation of atazanavir/ritonavir + 2NRTI in virologically suppressed patients, with a sustained benefit in terms of improved renal function and bone mineral density.

Switch to maraviroc with darunavir/r, both QD, in patients with suppressed HIV-1 was well tolerated but virologically inferior to standard antiretroviral therapy: 48-week results of a randomized trial.

OBJECTIVES: Primary study outcome was absence of treatment failure (virological failure, VF, or treatment interruption) per protocol at week 48. METHODS: Patients on 3-drug ART with stable HIV-1 RNA <50 copies/mL and CCR5-tropic virus were randomized 1:1 to maraviroc with darunavir/ritonavir qd (study arm) or continue current ART (continuation arm). RESULTS: In June 2015, 115 patients were evaluable for the primary outcome (56 study, 59 continuation arm). The study was discontinued due to excess of VF in the study arm (7 cases, 12.5%, vs 0 in the continuation arm, p = 0.005). The proportion free of treatment failure was 73.2% in the study and 59.3% in the continuation arm. Two participants in the study and 10 in the continuation arm discontinued therapy due to adverse events (p = 0.030). At VF, no emergent drug resistance was detected. Co-receptor tropism switched to non-R5 in one patient. Patients with VF reported lower adherence and had lower plasma drug levels. Femoral bone mineral density was significantly improved in the study arm. CONCLUSION: Switching to maraviroc with darunavir/ritonavir qd in virologically suppressed patients was associated with improved tolerability but was virologically inferior to 3-drug therapy.

Treatment simplification to atazanavir/ritonavir + lamivudine versus maintenance of atazanavir/ritonavir + two NRTIs in virologically suppressed HIV-1-infected patients: 48 week results from a randomized trial (ATLAS-M).

Background: Combination ART (cART)-related toxicities and costs have prompted the need for treatment simplification. The ATLAS-M trial explored 48 week non-inferior efficacy of simplification to atazanavir/ritonavir  +  lamivudine versus maintaining three-drug atazanavir/ritonavir-based cART in virologically suppressed patients. Methods: We performed an open-label, multicentre, randomized, non-inferiority study, enrolling HIV-infected adults on atazanavir/ritonavir + two NRTIs, with stable HIV-RNA <50 copies/mL and CD4 + >200 cells/mm 3 . Main exclusion criteria were hepatitis B virus coinfection, past virological failure on or resistance to study drugs, recent AIDS and pregnancy. Patients were randomly assigned 1:1 to either switch to 300 mg of atazanavir/100 mg of ritonavir once daily and 300 mg of lamivudine once daily (atazanavir/ritonavir + lamivudine arm) or to continue the previous regimen (atazanavir/ritonavir + two NRTIs arm). The primary study outcome was the maintenance of HIV-RNA <50 copies/mL at week 48 of the ITT-exposed (ITT-e) analysis with switch = failure. The non-inferiority margin was 12%. This study is registered at ClinicalTrials.gov, number NCT01599364. Results: Between July 2011 and June 2014, 266 patients were randomized (133 to each arm). After 48 weeks, the primary study outcome was met by 119 of 133 patients (89.5%) in the atazanavir/ritonavir + lamivudine arm and 106 of 133 patients (79.7%) in the atazanavir/ritonavir + two NRTIs arm [difference atazanavir/ritonavir + lamivudine versus atazanavir/ritonavir + two NRTIs arm: +9.8% (95% CI + 1.2 to + 18.4)], demonstrating non-inferiority and superior efficacy of the atazanavir/ritonavir + lamivudine arm. Virological failure occurred in two (1.5%) patients in the atazanavir/ritonavir + lamivudine arm and six (4.5%) patients in the atazanavir/ritonavir + two NRTIs arm, without resistance selection. A similar proportion of adverse events occurred in both arms. Conclusions: Treatment simplification to atazanavir/ritonavir + lamivudine showed non-inferior efficacy (superiority on post-hoc analysis) and a comparable safety profile over continuing atazanavir/ritonavir + two NRTIs in virologically suppressed patients.

Cognitive reserve and neuropsychological functioning in older HIV-infected people.

Progress in treatments has led to HIV+ patients getting older. Age and HIV are risk factors for neurocognitive impairment (NCI). We explored the role of cognitive reserve (CR) on cognition in a group of virologically suppressed older HIV+ people. We performed a multicenter study, consecutively enrolling asymptomatic HIV+ subjects ≥60 years old during routine outpatient visits. A comprehensive neuropsychological battery was administered. Raw test scores were adjusted based on Italian normative data and transformed into z-scores; NCI was defined according to Frascati criteria. All participants underwent the Brief Intelligence Test (TIB) and the Cognitive Reserve Index (CRI) questionnaire as proxies for CR. Relationships between TIB, CRI, and NCI were investigated by logistic or linear regression analyses. Sixty patients (85 % males, median age 66, median education 12, 10 % HCV co-infected, 25 % with past acquired immunodeficiency syndrome (AIDS)-defining events, median CD4 cells count 581 cells/µL, median nadir CD4 cells count 109 cells/µL) were enrolled. Twenty-four patients (40 %) showed Asymptomatic Neurocognitive Impairment. At logistic regression analysis, only CRI (OR 0.94; 95 % CI 0.91-0.97; P = 0.001) and TIB (OR 0.80; 95 % CI 0.71-0.90; P < 0.001) were associated with a lower risk of NCI. Higher CRI and TIB were significantly correlated with a better performance (composite z-score) both globally and at individual cognitive domains. Our findings highlight the role of CR over clinical variables in maintaining cognitive integrity in a virologically suppressed older HIV-infected population. A lifestyle characterized by experiences of mental stimulation may help to cope aging and HIV-related neurodegeneration.

Two Distinct Hepatitis C Virus Genotype 1a Clades Have Different Geographical Distribution and Association With Natural Resistance to NS3 Protease Inhibitors.

Background. Hepatitis C virus (HCV) genotype 1 is the most prevalent worldwide. Subtype 1a, compared with 1b, shows lower response rates and higher propensity to select for drug resistance to NS3 and selected NS5A and nonnucleoside NS5B inhibitors. Two distinct clades of subtype 1a have been described. Methods. Using Bayesian methodology, we performed a time-scaled phylogeny reconstruction of clade separation and characterized the geographic distribution, phylodynamics, and association with natural resistance variants of NS3 sequences from 362 patients carrying subtype 1a HCV. Results. All sequences segregated in 2 clearly distinct clades. Clade I showed an earlier origin from the common ancestor compared with clade II. Clade I virus was more prevalent in non-European countries, represented mostly by United States, compared with European (75.7% vs 49.3%; P < .001). The prevalence of the natural NS3 variant Q80K, associated with resistance to the macrocyclic protease inhibitor simeprevir, was detected in 51.6% of clade I and 0% of clade II (P < .001); clade I showed a lower genetic barrier for Q80K, whereas no sign of selective pressure at any protease inhibitor resistance-associated codon was detected. Conclusions. Hepatitis C virus subtype 1a clades have a clearly different distribution in Europe and the United States, and the natural resistance mutation Q80K is exclusively associated with clade I.

Antiretroviral neuropenetration scores better correlate with cognitive performance of HIV-infected patients after accounting for drug susceptibility.

BACKGROUND: The aim of the study was to explore how viral resistance and antiretroviral central nervous system (CNS) penetration could impact on cognitive performance of HIV-infected patients. METHODS: We performed a multicentre cross-sectional study enrolling HIV-infected patients undergoing neuropsychological testing, with a previous genotypic resistance test on plasma samples. CNS penetration-effectiveness (CPE) scores and genotypic susceptibility scores (GSS) were calculated for each regimen. A composite score (CPE-GSS) was then constructed. Factors associated with cognitive impairment were investigated by logistic regression analysis. RESULTS: A total of 215 patients were included. Mean CPE was 7.1 (95% CI 6.9, 7.3) with 206 (95.8%) patients showing a CPE≥6. GSS correction decreased the CPE value in 21.4% (mean 6.5, 95% CI 6.3, 6.7), 26.5% (mean 6.4, 95% CI 6.1, 6.6) and 24.2% (mean 6.4, 95% CI 6.2, 6.6) of subjects using ANRS, HIVDB and REGA rules, respectively. Overall, 66 (30.7%) patients were considered cognitively impaired. No significant association could be demonstrated between CPE and cognitive impairment. However, higher GSS-CPE was associated with a lower risk of cognitive impairment (CPE-GSSANRS odds ratio 0.75, P=0.022; CPE-GSSHIVDB odds ratio 0.77, P=0.038; CPE-GSSREGA odds ratio 0.78, P=0.038). Overall, a cutoff of CPE-GSS≥5 seemed the most discriminatory according to each different interpretation system. CONCLUSIONS: GSS-corrected CPE score showed a better correlation with neurocognitive performance than the standard CPE score. These results suggest that antiretroviral drug susceptibility, besides drug CNS penetration, can play a role in the control of HIV-associated neurocognitive disorders.

Baseline CD4(+) T-cell count and cardiovascular risk factors predict the evolution of cognitive performance during 2-year follow-up in HIV-infected patients.

BACKGROUND: The aim of our study was to better understand the dynamics between cardiovascular risk factors and immunological parameters in the evolution of cognitive performance in HIV+ patients. METHODS: We conducted a prospective longitudinal study, consecutively enrolling asymptomatic HIV+ subjects during routine outpatient visits at two clinical centres. At baseline and after 2 years, all patients underwent a comprehensive neuropsychological battery. Common carotid intima-media thickness (cIMT) was also measured. RESULTS: A total of 150 patients completed the study (77% males, median age 46 years, 20% with past AIDS-defining events, 95% on cART, 88% with HIV-RNA<50 copies/ml). After a 2-year follow-up, there was no difference in the proportion of patients with cognitive impairment (32% versus 33% at baseline; P=1.00). However, a significantly worse memory performance was observed (z score mean change -0.51, sd 1.05; P=0.001). At multivariate analysis, baseline dyslipidaemia (OR 2.7, 95% CI 1.1, 7.1; P=0.037) showed a significant association with a higher risk of memory impairment at 2-year follow-up, while higher baseline CD4(+) T-cell count (OR 0.80 per 100 cells/µl higher; 95% CI 0.66, 0.97; P=0.026) was found to be a protective factor, adjusting for the presence of a memory impairment at baseline. When the analysis was restricted to patients who did not change antiretroviral therapy during the study period (n=109), baseline cIMT (OR 14.6 per 0.1 mm higher; 95% CI 1.1, 189.9; P=0.041) also emerged as an independent risk factor for memory impairment at 2-year follow-up. CONCLUSIONS: Immunological parameters and cardiovascular risk factors are independently associated with the evolution of cognitive status in HIV+ patients.

Liver fibrosis is associated with cognitive impairment in HIV-positive patients.

INTRODUCTION: The aim of our study was to investigate the potential relationship between liver fibrosis (LF) and cognitive performance in HIV+ patients. MATERIALS AND METHODS: We performed a cross-sectional cohort study by consecutively enrolling HIV+ patients during routine outpatient visits at two clinical centres in Italy. Subjects with decompensated liver disease were excluded. All subjects underwent a comprehensive neuropsychological battery exploring memory, attention, psychomotor speed and language; cognitive impairment was defined as at least two abnormal [1.5 SD below the mean for appropriate norms] cognitive domains. LF was explored by calculating FIB4 index; in a subgroup of patients, LF was also assessed by transient elastography. Factors associated with cognitive impairment were investigated by logistic regression models. RESULTS: A total of 413 patients [77% males, median age 46 (IQR 39-52), 17% with past AIDS-defining events, 19% past IDU, 3% with diabetes, 94% on cART, 90% with HIV RNA <50 copies/mL, 18% co-infected with HCV] were enrolled. Seventeen patients (4%) had FIB4 >3.25 and 14/129 (3%) had liver stiffness >14KPa. Forty-seven patients (11%) were diagnosed with cognitive impairment. At multivariate analyses patients with FIB4 >1.45 showed a higher risk of cognitive impairment in comparison with those with lower values (OR 2.19, 95% CI 1.02-4.72; p=0.044) after adjusting for education (OR 0.79, 95% CI 0.71-0.88; p<0.001), past IDU (OR 1.69, 95% CI 0.67-4.23; p=0.264), diabetes (OR 2.35, 95% CI 0.62-8.86; p=0.207), HIV RNA <50 copies/mL (OR 0.47, 95% CI 0.19-1.14; p=0.095) and HCV co-infection (OR 0.88, 95% CI 0.33-2.39; p=0.807). Analyzing any single cognitive domain, a higher risk of abnormal psychomotor speed was associated with fibroscan score >14KPa in comparison with fibroscan score <7KPa (OR 285.07; 95% CI 2.42-33574.06; p=0.020) after adjusting for education (OR 0.54, 95% CI 0.31-0.92; p=0.024), age (for 10 years increase) (OR 2.03, 95% CI 0.55-7.53; p=0.288), past IDU (OR 4.43, 95% CI 0.35-7.57; p=0.526), HIV RNA <50 copies/mL (OR 0.01, 95% CI 0.00-0.18; p=0.003), HIV history (for 1 year increase) (OR 0.96, 95% CI 0.83-1.12; p=0.641), CD4 cells count at nadir (OR 1.10, 95% CI 0.56-2.16; p=0.779), and HCV co-infection (OR 0.06; 95% CI 0.00-1.93; p=0.113). CONCLUSIONS: In HIV-infected patients higher LF, estimated through non-invasive methods, is associated to a higher risk of cognitive impairment.

Simplification to atazanavir/ritonavir+lamivudine in virologically suppressed HIV-infected patients: 24-weeks interim analysis from ATLAS-M trial.

INTRODUCTION: We report interim 24-weeks efficacy data of ATLAS-M trial, a phase IV, multicentre, open-label, randomized study designed to show 48-weeks, non-inferior efficacy (margin of -12%) of treatment simplification to atazanavir/ritonavir (ATV/r)+lamivudine (3TC) versus maintaining 3-drugs ATV/r-based cART. METHODS: Subjects on ATV/r+2 NRTIs, without previous treatment failure (TF), with HIV-RNA <50copies/mL for >3 months and CD4>200 cells/mm(3) for >6 months were eligible. At baseline, patients were randomized to switch to ATV/r+3TC (arm one) or to maintain the original 3-drug regimen (arm two). PRIMARY ENDPOINT: proportion of patients free of TF at week 48. TF was defined as treatment modification for any reason, including virological failure (VF=two consecutive HIV-RNA>50 copies/mL or a single value >1000 copies/mL). Enrollment of 266 patients was planned. RESULTS: A total of 266 patients (78% males, median age 44 years, median CD4 603 cells/µL, 79% treated with a tenofovir-containing backbone) were enrolled. At the time of analysis, 24 weeks data were available for 84 and 87 patients in arm one and two, respectively. At baseline, subjects in the two arms did not differ for the main characteristics. At 24 weeks, at the intention to treat analysis the proportion of patients free of TF was 91.7% (95% CI 85.8-97.6) and 85.1% (95% CI 77.6-92.6) in arm one and two, respectively (difference +6.6%, 95% CI -2.9/+16.1). VF was observed in two patients randomized to arm one (one at baseline, before treatment simplification) and one to arm two without resistance mutations. Clinical and laboratory adverse events occurred at similar rates in the two arms. At week 24, patients in arm one showed a greater increase in CD4 (mean change +90 vs +10 cells/µL, p=0.007). A greater increase in total cholesterol (+18 vs -2 mg/dL, p<0.001), HDL (+4 vs +0 mg/dL, p=0.001) and LDL (+12 vs +0 mg/dL, p=0.001) was also observed in arm one without differences in other lipid parameters. Renal function showed a significant improvement in arm one (mean change in eGFR +5 vs -2 mL/min/1.73m(2) in arm two, p=0.001). No significant differences in bilirubin levels or other laboratory parameters were observed between the two arms. CONCLUSIONS: This interim analysis suggests a 24-weeks non-inferior efficacy of treatment simplification to ATV/rit+3TC as compared to continuation of ATV/rit +2 NRTI in virologically suppressed patients. Follow-up until 48-weeks is scheduled to confirm these data.

Single tablet regimens are associated with reduced Efavirenz withdrawal in antiretroviral therapy naïve or switching for simplification HIV-infected patients.

BACKGROUND: Efavirenz (EFV) administration is still controversial for its high rates of interruption mainly related to central nervous system side effects (CNS-SE). Aim of the study was to define if single tablet regimen (STR) as compared to bis-in-die (BID) or once-daily (OD) with ≥2 pills-a-day EFV formulations reduced the risk of interruption. METHODS: Patients starting any cART regimen including EFV + 2NRTIs or switching to EFV + 2NRTIs for simplification after virological suppression were retrospectively selected. Incidence, probability and prognostic factors of interruption by different causes were assessed by survival analysis and Cox regression model. RESULTS: Overall, 553 patients starting EFV-containing regimens were included: 38.2% started BID regimen, 44.5% OD regimens ≥2 pills and 17.4% STR. The overall proportion of EFV interruption was 37.4% at 4 years; at the same time point, interruptions for virological failure and toxicity were 8.8% and 16.5% (8% for CNS-SE), respectively. Starting EFV co-formulated in STR was associated with lower proportion of overall interruption at 4 years (17.1% vs. 40.6%, p < 0.01). Only one virological failure was observed with STR up to 4 years (1.1% vs. 10.3% in non-STR, p = 0.051). STR also accounted for lower proportion of interruption by patient decision (1.5% vs. 11.8%, p = 0.01). No differences of interruption by overall toxicity and CNS-SE were observed. In multivariable analysis, STR and male gender were associated with lower risk of EFV interruption, while higher CD4 nadir and IDU with higher risk. CONCLUSIONS: In our experience, starting EFV co-formulated in STR was associated with lower virological failure and higher adherence, despite a similar proportion of CNS toxicity, thus reducing the risk of treatment interruption.

Prevalence and distribution of human papillomavirus genotype in south eastern Italy, in the period 2006-2011: implications for intervention.

Persistent infection of High Risk (HR) Human papillomavirus (HPV) infection can lead to cervical cancer. The HPV genotypes are found worldwide, but important regional variations have been found. For a population-based HPV type prevalence study to assess the effect of existing and new prevention methods, frequently updated information on the burden of cervical cancer is essential. We evaluated the prevalence of HPV genotypes in a volunteer population screened for cervical cancer at the Local Health Unit (LHU) of Lecce. A total of 9,720 women were studied. The tests were performed by INNO-Lipa HPV Genotyping and LINEAR ARRAY HPV Genotyping Test. The overall HPV prevalence was 29.7% (95% CI, 28.8-30.6) for any HPV DNA. The prevalent type for all age groups was HPV 16 (7.4%; CI, 6.9-7.9) followed by HPV 31 (3.4%; CI, 3.0-3.7), 51 (3.0%; CI, 2.6-3.3), 52 (2.7%; CI, 2.3-3.0) and 58 (2.4%; CI, 2.1-2.7). HPV 53 was the most common low-risk HPV type with prevalence rate of 3.5 (CI, 3.1-3.8), followed by HPV 66 (3.0; CI, 2.6-3.3), 6 (2.9; CI, 2.6-3.2) and 42 (2.5; CI, 2.2-2.8). Multiple infections were present in 13.6% of HPV-tested women (CI, 12.9-14.3). Among these, the most common combination was of HPV 16 and HPV 52 genotypes. This study reports high prevalence of HPV infection and may serve as a valuable reference for assessing the impact of HPV vaccination programs. Furthermore, it supports the need for new vaccines that contain the most common HPV genotypes present in the population.