Efficacy and safety of dolutegravir/lamivudine in virologically suppressed female participants: week 48 data from the pooled TANGO and SALSA studies.

OBJECTIVES: Women represent >50% of people with HIV globally but have historically been underrepresented in clinical trials. We evaluated the efficacy and safety of switching to dolutegravir/lamivudine (DTG/3TC) vs continuing their current antiretroviral regimen (CAR) by sex assigned at birth (female and male) in virologically suppressed adults with HIV-1 without prior virological failure in a pooled analysis of two randomized controlled trials. METHODS: This analysis included 48-week data from the phase 3 TANGO and SALSA studies. Primary and key secondary endpoints included proportions of participants with HIV-1 RNA ≥50 and <50 copies/mL at week 48, respectively. Safety was also assessed. RESULTS: Of 1234 participants, 250 (DTG/3TC, n = 133; CAR, n = 117) were female at birth. Week 48 proportions of participants with Snapshot HIV-1 RNA ≥50 copies/mL were similar regardless of sex at birth (DTG/3TC vs CAR: female, <1% [1/133] vs 2% [2/117]; male, <1% [1/482] vs <1% [3/502]). Proportions with HIV-1 RNA <50 copies/mL were high across sexes and treatment groups (DTG/3TC vs CAR: female, 91% [121/133] vs 89% [104/117]; male, 94% [455/482] vs 94% [471/502]). Immunological response with DTG/3TC was slightly higher in female participants. Incidences of adverse events leading to withdrawal and serious adverse events were low and comparable between treatment groups and across sexes. Weight gain was higher with DTG/3TC than with CAR among female participants aged ≥50 years (treatment difference 2.08 kg [95% confidence interval 0.40-3.75]). CONCLUSIONS: Results confirm the robustness of DTG/3TC as a switch option in virologically suppressed females with HIV-1, with outcomes similar to those in males.

Analysing the efficacy and tolerability of dolutegravir plus either rilpivirine or lamivudine in a multicentre cohort of virologically suppressed PLWHIV.

OBJECTIVES: We aimed to investigate and compare the efficacy and safety of two dolutegravir-based two-drug regimens: dolutegravir + lamivudine versus dolutegravir + rilpivirine. METHODS: We analysed a cohort of people living with HIV (PLWHIV) switching to dolutegravir + lamivudine or dolutegravir + rilpivirine. We excluded from the analysis PLWHIV with no available pre-switch genotypic test or with a known resistance mutation to one of the study drugs. We evaluated incidence of virological failure (VF) and treatment discontinuation (TD), as well as changes in immunological and metabolic parameters. RESULTS: We enrolled 592 PLWHIV: 306 in the lamivudine group and 286 in the rilpivirine group. We observed nine VFs in the lamivudine group [1.4 VF per 100 patient-years of follow-up (PYFU)] and four VFs in the rilpivirine group (0.6 VF per 100 PYFU). Subsequent genotypic analysis showed no acquired resistance-associated mutations in those experiencing VF. Estimated probability of maintaining virological suppression at 144 and 240 weeks were 96.6% and 92.7%, respectively, in the lamivudine group and 98.7% and 98.7%, respectively, in the rilpivirine group (log-rank P = 0.172). The estimated probability of maintaining study regimen at Week 240 was 82.3% in the lamivudine group and 85.9% in the rilpivirine group (log-rank P = 0.018). We observed a significant improvement in CD4+ cell count at Week 240 in the lamivudine group (P = 0.012); in the rilpivirine group we registered a significant increase in CD4/CD8 ratio (P = 0.014). CONCLUSIONS: Both analysed strategies are effective and safe as switch strategies in clinical practice, with a low incidence of VF and a favourable immunological recovery, even in the long term.

Virological outcomes with dolutegravir plus either lamivudine or two NRTIs as switch strategies: a multi-cohort study.

OBJECTIVES: To compare the efficacy of dolutegravir plus lamivudine dual therapy (DT) with that of dolutegravir plus two NRTIs triple therapy (TT) as switch strategies. METHODS: A multicentre cohort of HIV-positive, HBsAg-negative patients with viral suppression (HIV-RNA ≤50 copies/mL) switching to DT or TT was retrospectively selected from the ARCA database. The effect of DT versus TT on virological failure (VF; defined as two consecutive HIV-RNA values >50 copies/mL or one HIV-RNA value ≥200 copies/mL) was evaluated by multivariable Cox regression models, overall and after stratifying for the presence of NRTI resistance-associated mutations (RAMs). RESULTS: From December 2014 to June 2020, 628 patients were eligible: 118 (18.8%) started tenofovir/emtricitabine/dolutegravir, 306 (48.7%) abacavir/lamivudine/dolutegravir and 204 (32.5%) lamivudine/dolutegravir. The DT group had significantly higher nadir and baseline CD4 counts, a higher duration of viral suppression and a lower prevalence of RAMs at historical genotype. Overall, 41 VF occurred after a median of 1.7 years of follow-up, with a lower, but not statistically significant, rate for DT [versus TT, adjusted HR (aHR) = 0.58, 95% CI = 0.25-1.34]. However, DT was associated with less VF in the absence of RAMs when compared with tenofovir-based TT (aHR = 0.20, 95% CI = 0.06-0.67), but not with abacavir-based TT (aHR = 0.43, 95% CI = 0.17-1.11). Conversely, in the setting of pre-existing M184V/I, DT showed a trend to increased risk of VF (versus tenofovir-based TT, aHR = 137.50, 95% CI = 4.24-4464.06; versus abacavir-based TT, aHR = 33.88, 95% CI = 1.75-656.47). CONCLUSIONS: Lamivudine/dolutegravir maintenance DT showed similar efficacy to dolutegravir-based TT; however, past M184V/I may favour VF.

Association between colorectal cancer and Streptococcus gallolyticus subsp. pasteuranus (former S. bovis) endocarditis: clinical relevance and cues for microbiota science. Case report and review of the literature.

OBJECTIVE: The purpose of this paper is to contextualize the case of a patient with a synchronous diagnosis of colorectal cancer (CRC) and endocarditis from S. gallolyticus subsp. pasteuranus (former S. Bovis) within the current evidence, in order to determine if this condition is indicative of an underlying CRC and if it has any pathophysiologic significance. PATIENTS AND METHODS: First, we describe the clinical case. Then, we review the literature focused on the association between infections from the former S. Bovis group and CRC and on the possible role of certain microbiota species on the occurrence of CRC. At last, we discuss the implications of this case considering the current evidence. RESULTS: There is a strong association between all the species of the former S. Bovis group and CRC. There is initial evidence that these bacteria may contribute to CRC by a genomic passenger mechanism. CONCLUSIONS: There are two main conclusions for this paper. The first one is that CRC neoplasms and endocarditis from all species of the former S. bovis group have a strong association. Any case of infection by these subspecies should prompt to a diagnostic completion by colonoscopy. The second one is that there is an increased need for detailed reports/series and original articles based on the evaluation of gut microbiota in patients with CRC, with the aim to clarify if the association between bacteria and CRC is causative or sporadic and to better understand the possible causative mechanism of specific bacteria in initiating and promoting CRC.

Transmitted drug resistance to NRTIs and risk of virological failure in naïve patients treated with integrase inhibitors.

OBJECTIVES: Nucleoside reverse transcriptase inhibitor (NRTI) transmitted drug resistance mutations (TDRMs) could increase the risk of virological failure (VF) of first-line integrase strand transfer inhibitor (InSTI)-based regimens. METHODS: Patients starting two NRTIs (lamivudine/emtricitabine plus abacavir/tenofovir) plus raltegravir or dolutegravir were selected from the EuResist cohort. The role of NRTI genotypic susceptibility score and of specific TDRMs in VF (i.e. two consecutive viral loads > 50 HIV-1 RNA copies/mL or a single viral load ≥ 200 copies/mL after 3 months from antiretroviral therapy start) was evaluated in the overall population and according to the InSTI employed. RESULTS: From 2008 to 2017, 1095 patients were eligible for the analysis (55.5% men, median age 39 years). In all, 207 VFs occurred over 1023 patient-years of follow-up. The genotypic susceptibility score (GSS) had no effect on the risk of VF in the overall population. However, the presence of M184V/I independently predicted VF of raltegravir- but not dolutegravir-based therapy when compared with a fully-active backbone [adjusted hazard ratio (aHR) = 3.09, P = 0.035], particularly when associated with other non-thymidine analogue mutations (aHR = 27.62, P = 0.004). Higher-zenith HIV-RNA and lower nadir CD4 counts independently predicted VF. CONCLUSIONS: NRTI backbone TDRMs increased the risk of VF with raltegravir-based but not dolutegravir-based regimens.

Hospital reengineering against COVID-19 outbreak: 1-month experience of an Italian tertiary care center.

OBJECTIVE: The recent outbreak of SARS-CoV-2 infection in Italy has resulted in a sudden and massive flow of patients into emergency rooms, and a high number of hospitalizations with the need for respiratory isolation. Massive admission of patients to the Policlinico "Agostino Gemelli" Foundation of Rome, Italy, determined the need for reengineering the entire hospital. MATERIALS AND METHODS: In this article, we consider some of the structural and organizational changes that have been necessary to deal with the emergency, with particular reference to non-intensive medicine wards, and the preventive measures aimed at limiting the spread of SARS-CoV-2 infection among hospital staff and patients themselves. RESULTS: 577 staff members were subjected to molecular tests in 1-month period and 3.8% of the total were positive. 636 patients admitted to the COVID-19 pathway were included and analyzed: 45.4% were identified as SARS-CoV-2 positive. More SARS-CoV-2 negative patients were discharged in comparison to SARS-CoV-2 positive patients (59% vs. 41%, respectively). On the other hand, more SARS-CoV-2 positive patients were transferred to ICUs in comparison to SARS-CoV-2 negative patients (16% vs. 1%, respectively). Occurrence of death was similar between the two groups, 11% vs. 7%, for SARS-CoV-2 negative and positive patients, respectively. 25% of ≥80 years old SARS-CoV-2 positive patients died during the hospitalization, while death rate was lower in other age groups (5% in 70-79 years old patients and 0% in remaining age groups). CONCLUSIONS: Rapid hospital reengineering has probably had an impact on the management of patients with and without SARS-CoV-2 infection, and on in-hospital mortality rates over the reporting period.

Viro-immunological efficacy and tolerability of dolutegravir-based regimens compared to regimens based on other integrase strand inhibitors, protease inhibitors or non-nucleoside reverse transcriptase inhibitors in patients with acute HIV-1 infection: A multicenter retrospective cohort study.

OBJECTIVES: The aim of this study was to compare the tolerability and viro-immunological efficacy of dolutegravir-based regimens (DTG group) with regimens based on EVG, RAL, PI or NNRTI (NODTG group) in patients with acute HIV-1 infections (AHI). METHODS: All patients diagnosed with AHI and on antiretroviral therapy (ART) between January 2015 and December 2017 from five centers in Italy were included and followed-up to 30th April 2018. AHI was defined by the presence of the positive p24 antigen with negative or indeterminate western blot. RESULTS: Forty-three patients were enrolled: 20 in the DTG group, 23 in the NODTG group. Nine patients (20.9%; four in the DTG group, five in the NODTG group) were prescribed a four-drug regimen. In the cohort, 81.4% were Italian and 83.7% were male, with a median age of 41 years (interquartile range [IQR] 31-48). Median time between HIV diagnosis and ART initiation was 12 days (IQR 5-28). Seven patients harbored a virus with transmitted mutations at baseline (16.2%), all were in the DTG group (P=0.005). All patients had undetectable HIV-RNA at the end of follow-up except two patients, one of whom had 57 copies and one who was lost to follow-up. In Kaplan-Meier analysis, time to virological suppression was similar in the two groups (log rank: P= 0.7155). After achieving virological suppression, four patients stopped ART because of toxicity: two on DTG, two on EVG for neurological and gastrointestinal toxicity, respectively. CONCLUSION: In our setting, ART in AHI is started very early. DTG showed good viro-immunological efficacy even in the presence of NRTI-transmitted mutations. DTG interruptions were rare.

Lamivudine-based maintenance antiretroviral therapies in patients living with HIV-1 with suppressed HIV RNA: derivation of a predictive score for virological failure.

OBJECTIVES: Two-drug antiretroviral regimens based on lamivudine (3TC) plus either a protease inhibitor (PI) or dolutegravir (DTG) are becoming increasingly popular in switch strategies. Our goal was to derive a predictive score for virological failure (VF). METHODS: We retrospectively analysed data for a cohort of 587 virologically suppressed (HIV RNA < 37 HIV-1 RNA copies/mL), adult (≥ 18 years old) patients starting lamivudine plus either a boosted PI or dolutegravir. Predictors of VF (defined as a single HIV RNA measurement ≥ 1000 copies/mL or two consecutive HIV RNA measurements ≥ 50 copies/mL) were identified using a multivariate Cox regression model. A 'weighted' score was assigned to each variable associated with VF; the discriminative power of the score obtained was expressed as the area under the receiver-operator characteristic curve (ROC-AUC). RESULTS: During a median 2 years of follow-up time, 35 VFs occurred; predictors of VF were baseline residual HIV RNA between 20 and 36 copies/mL, African ethnicity, ≥ 10 therapeutic lines, the presence of at least one resistance-associated mutation (RAM) for resistance to current drugs (excluding M184V), a non-B viral subtype and a baseline CD4 count < 200 cells/µL. A score of 2 was assigned to non-B viral subtype, 3 to residual viraemia ≥ 20 copies/mL, ≥ 10 previous therapeutic lines and African ethnicity, 4 to baseline CD4 count < 200 cells/µL, and 7 to the presence of at least one RAM (excluding M184V). The ROC-AUC was 0.67 (95% confidence interval 0.57-0.77). CONCLUSIONS: The presence of at least one RAM, higher residual viraemia and African ethnicity were among the major predictors of VF in our cohort. Studies with larger sample sizes are warranted to improve the predictive value of the derived score.

Trends of hospitalisations rates in a cohort of HIV-infected persons followed in an Italian hospital from 1998 to 2016.

Here we evaluated hospitalisation rates and associated risk factors of human immunodeficiency virus (HIV)-infected individuals who were followed up in an Italian reference hospital from 1998 to 2016. Incidence rates (IR) of hospitalisations were calculated for five study periods from 1998 to 2016. The random-effects Poisson regression model was used to assess risk factors for hospitalisation including demographic and clinical characteristics. To consider that more events may occur for the same subject, multiple failure-time data analysis was also performed for selected causes using the Cox proportional hazards model. We evaluated 2031 patients. During 13 173 person-years (py) of follow-up, 3356 hospital admissions were carried out for 756 patients (IR: 255 per 1000 py). IR decreased significantly over the study period, from 634 in 1998-2000 to 126 per 1000 py in 2013-2016. Major declines were detected for AIDS-defining events, non-HIV/AIDS-related infections and neurological diseases. Older age, female sex, longer HIV duration and HCV coinfection were associated with a higher hospitalisation risk, whereas higher CD4 nadir and antiretroviral therapy were associated with a reduced risk. Influence of advanced HIV disease markers declined over time. Hospitalisation rates decreased during the study period in most causes. The relative weight of hospitalisations for non-AIDS-related tumours, cardiovascular, respiratory and kidney diseases increased during the study period, whereas those for AIDS-defining events declined.

Efficacy and safety of switching to dolutegravir plus emtricitabine/tenofovir disoproxil fumarate (TDF) or elvitegravir/cobicistat/emtricitabine/TDF in virologically suppressed HIV-infected patients in clinical practice: results from a multicentre, observational study.

OBJECTIVES: The aim of the study was to compare the efficacy and tolerability of switching antiretroviral therapy to dolutegravir + emtricitabine/tenofovir disoproxil fumarate (TDF) with those of switching to elvitegravir/cobicistat/emtricitabine/TDF in clinical practice. METHODS: In a multicentre real-life observational study, we analysed data for HIV-infected patients on antiretroviral treatment with viral load < 50 HIV-1 RNA copies/mL switching to dolutegravir + emtricitabine/TDF (dolutegravir group) or elvitegravir/cobicistat/emtricitabine/TDF (elvitegravir group). Follow-up was censored at 48 weeks. RESULTS: The 48-week estimated proportion maintaining virological efficacy was 96.1% with dolutegravir (n = 123) and 95.4% with elvitegravir (n = 186; P = 0.941). Patients in the dolutegravir group showed more treatment discontinuations, but these were mainly as a result of simplification. The elvitegravir group showed more discontinuations because of renal adverse events (2.7% versus 0% with dolutegravir). Interestingly, no difference was observed between the two regimens in central nervous system toxicity-related discontinuations. Switching to dolutegravir was associated with a better blood lipid profile. CONCLUSIONS: Switching to dolutegravir + emtricitabine/TDF was associated with similar efficacy and tolerability to switching to elvitegravir/cobicistat/emtricitabine/TDF in virologically suppressed patients in clinical practice, although reasons for discontinuation showed differences between regimens. These results should be interpreted with caution, as this is a nonrandomized comparison.

SLC22A2 variants and dolutegravir levels correlate with psychiatric symptoms in persons with HIV.

BACKGROUND: Neuropsychiatric symptoms (NPs) have been reported with dolutegravir use. We hypothesized that increasing dolutegravir trough concentrations (Ctrough) and/or polymorphism in the SLC22A2 gene, encoding the organic cation transporter-2 (OCT2), which is involved in monoamine clearance in the CNS and is inhibited by dolutegravir, might be associated with NPs. METHODS: A cross-sectional cohort of HIV-positive patients treated with a dolutegravir-containing regimen underwent determination of allelic discrimination for SLC22A2 808 C → A polymorphism and dolutegravir Ctrough. The Symptom Checklist-90-R [investigating 10 psychiatric dimensions and reporting a general severity index (GSI)], a self-reported questionnaire and the Mini-International Neuropsychiatric Interview were offered to investigate current NPs. The effects of dolutegravir Ctrough and the SLC22A2 gene variant on NPs were explored by multivariable logistic regression. RESULTS: A cohort of 203 patients was analysed: 71.4% were male, with median age 51 years and 11 years of ART exposure. Median time on dolutegravir was 18 months. Dolutegravir was associated with different antiretroviral combinations (mainly lamivudine, 38.9%, and abacavir/lamivudine, 35.5%). SLC22A2 CA genotype was independently associated with an abnormal GSI [adjusted OR (aOR) 2.43; P = 0.072], anxiety (aOR 2.61; P = 0.044), hostility (aOR 3.76; P = 0.012) and with moderate to severe headache (aOR 5.55; P = 0.037), and dolutegravir Ctrough was associated with hostility (fourth versus first quartile aOR 6.70; P = 0.007) and psychoticism (fourth versus first quartile aOR 19.01; P = 0.008). Other NPs were not associated with SLC22A2 polymorphism or dolutegravir Ctrough. CONCLUSIONS: A variant of the OCT2-encoding gene, in addition to or in synergy with higher dolutegravir Ctrough, is associated with a set of NPs observed during dolutegravir therapy.

Individual patient data meta-analysis of randomized controlled trials of dual therapy with a boosted PI plus lamivudine for maintenance of virological suppression: GeSIDA study 9717.

Background: Dual therapy (DT) with a ritonavir-boosted PI (PI/r) plus lamivudine has proven non-inferior (12% margin) to triple therapy (TT) with PI/r plus two nucleos(t)ide reverse transcriptase inhibitors [N(t)RTIs] in four clinical trials. It remains unclear whether DT is non-inferior based on the US FDA endpoint (virological failure with a margin of 4%) or in specific subgroups. Methods: We performed a systematic search (January 1990 to March 2017) of randomized controlled trials that compared switching of maintenance ART from TT to DT. The principal investigators were contacted and agreed to share study databases. The primary endpoint was non-inferiority of DT to TT based on the current FDA endpoint (4% non-inferiority margin for virological failure at week 48). We also analysed whether efficacy was modified by gender, active HCV infection and type of PI. Effect estimates and 95% CIs were calculated using generalized estimating equation-based models. Results: We found 881 references that yielded eight articles corresponding to four clinical trials (1051 patients). At week 48, 4% of patients on DT versus 3.04% on TT had experienced virological failure (difference 0.9%; 95% CI -1.2% to 3.1%), and 84.7% of patients on DT versus 83.2% on TT had <50 copies of HIV RNA/mL (FDA snapshot algorithm) (difference 1.4%; 95% CI -2.8% to 5.8%). Gender, active HCV infection and type of PI had no effect on differences in treatment efficacy between DT and TT. Conclusions: DT was non-inferior to TT using both current and past FDA endpoints. The efficacy of DT was not influenced by gender, active HCV infection status, or type of PI.

Evolution of transmitted HIV-1 drug resistance and viral subtypes circulation in Italy from 2006 to 2016.

OBJECTIVES: The aim was to evaluate the evolution of transmitted HIV-1 drug resistance (TDR) prevalence in antiretroviral therapy (ART)-naïve patients from 2006 to 2016. METHODS: HIV-1 sequences were retrieved from the Antiviral Response Cohort Analysis (ARCA) database and TDR was defined as detection of at least one mutation from the World Health Organization (WHO) surveillance list. RESULTS: We included protease/reverse transcriptase sequences from 3573 patients; 455 had also integrase sequences. Overall, 68.1% of the patients were Italian, the median CD4 count was 348 cells/µL [interquartile range (IQR) 169-521 cells/µL], and the median viral load was 4.7 log10 HIV-1 RNA copies/mL (IQR 4.1-5.3 log10 copies/mL). TDR was detected in 10.3% of patients: 6% carried mutations to nucleos(t)ide reverse transcriptase inhibitors (NRTIs), 4.4% to nonnucleos(t)ide reverse transcriptase inhibitors (NNRTIs), 2.3% to protease inhibitors (PIs), 0.2% to integrase strand transfer inhibitors (INSTIs) and 2.1% to at least two drug classes. TDR declined from 14.5% in 2006 to 7.3% in 2016 (P = 0.003): TDR to NRTIs from 9.9 to 2.9% (P = 0.003) and TDR to NNRTIs from 5.1 to 3.7% (P = 0.028); PI TDR remained stable. The proportion carrying subtype B virus declined from 76.5 to 50% (P < 0.001). The prevalence of TDR was higher in subtype B vs. non-B (12.6 vs. 4.9%, respectively; P < 0.001) and declined significantly in subtype B (from 17.1 to 8.8%; P = 0.04) but not in non-B subtypes (from 6.1 to 5.8%; P = 0.44). Adjusting for country of origin, predictors of TDR were subtype B [adjusted odds ratio (AOR) for subtype B vs. non-B 2.91; 95% confidence interval (CI) 1.93-4.39; P < 0.001], lower viral load (per log10 higher: AOR 0.86; 95% CI 0.75-0.99; P = 0.03), site in northern Italy (AOR for southern Italy/island vs. northern Italy, 0.61; 95% CI 0.40-0.91; P = 0.01), and earlier calendar year (per 1 year more recent: AOR 0.95; 95% CI 0.91-0.99; P = 0.02). CONCLUSIONS: The prevalence of HIV-1 TDR has declined during the last 10 years in Italy.

Efficacy and tolerability of lamivudine plus dolutegravir as a switch strategy in a multicentre cohort of patients with suppressed HIV-1 replication.

OBJECTIVES: We evaluated the efficacy and tolerability of lamivudine + dolutegravir in a cohort of HIV-1 infected, treatment-experienced patients with undetectable HIV-RNA. METHODS: Time to treatment discontinuation (TD) and virological failure (VF) and their predictors were assessed in a multicenter cohort of HIV-1 infected patients, starting lamivudine + dolutegravir after reaching viral suppression. Secondary objective was the evaluation of changes in lipid profile, renal and immunological functions at week 48. RESULTS: We enrolled 206 patients (72.8% male, with 51 years median age), who mainly switched their antiretroviral therapy for simplification (32.5%) or drug toxicity (54.5%). The estimated probability of maintaining virological suppression at 48 and 96 weeks was 98.2% and 95.1%, respectively. VF was independently predicted by cumulative time on antiretroviral therapy. The estimated probability of remaining on lamivudine plus dolutegravir was 86.7% and 80.5% at week 48 and 96, respectively. A significant improvement in immunological function (CD4 count and CD4/CD8 ratio) was evidenced at week 48, as well as a decrease in total cholesterol/HDL ratio, triglycerides and estimated glomerular filtration rate. CONCLUSIONS: Lamivudine plus dolutegravir was effective in maintaining viral suppression in our cohort and led to an improvement in metabolic and immunologic functions.

An outbreak of acute hepatitis A among young adult men: clinical features and HIV coinfection rate from a large teaching hospital in Rome, Italy.

OBJECTIVES: Italy is a low-incidence region for hepatitis A; however, during the last 2 years an increase in the incidence of hepatitis A virus (HAV) infection was reported in Europe. The aim of this study was to describe this recent outbreak. METHODS: We retrospectively analysed all cases of acute hepatitis A diagnosed at our laboratory between January 2010 and June 2017. We evaluated the following variables at the time of diagnosis: sex, age, nationality, glutamic oxaloacetic transaminase (GOT/AST), glutamic pyruvic transaminase (GPT/ALT), bilirubin concentration, international normalized ratio (INR) and the presence or absence of anti-HIV-1/2 antibodies. Hospitalization was also considered. We analysed these parameters using the χ2 test and Mann-Whitney U-test. RESULTS: A total of 225 cases were analysed; 82.7% were in male patients, 94.2% were in Italians and the median age of the patients was 36.4 years. At diagnosis, the median GOT value was 306 U/L, the median GPT was 1389 U/L, and the median total bilirubin value was 5.88 mg/dL. Hospitalization was required for 142 patients, with a median duration of hospital stay of 8.5 days. In 2016-2017 we registered 141 cases, with a higher prevalence of male patients, higher GPT values and a higher prevalence of patients aged 20-39 years compared with older (2010-2015) cases. Homosexual intercourse was reported as the HAV risk factor in 70.2% of patients. HIV serology was available for 120 patients: 24 were HIV-positive, four of whom represented new diagnoses. HIV-positive patients showed lower bilirubin and GPT values and fewer hospitalizations than HIV-negative patients. CONCLUSIONS: In 2016-2017, we saw a rise in the number of hepatitis A cases, with a higher prevalence of adult male patients. No significant differences regarding the prevalence of HIV coinfection emerged.

Natural NS5A inhibitor resistance associated substitutions in hepatitis C virus genotype 1 infected patients from Italy.

OBJECTIVES: Genetic variability in NS5A is associated with different levels of resistance to the currently licensed NS5A inhibitors. The aim of this study was to detect NS5A inhibitor resistance associated substitutions (RASs) in hepatitis C virus (HCV) genotype 1 (GT1) patients who are naive to direct-acting HCV antivirals. METHODS: Amplification, Sanger sequencing and phylogenetic analysis of the HCV NS5A region were performed on plasma obtained from 122 consecutive patients with HCV chronic infection attending four different clinics in Italy. RESULTS: NS5A inhibitor RASs were detected in 14/61 (23.0%) HCV GT1b and 3/61 (4.9%) HCV GT1a infected patients (p 0.007). The pan-genotypic RAS Y93H was detected in 1 (1.6%) GT1a and 4 (6.6%) GT1b patients. GT1a sequences clustered into two different clades with RASs detected in 1/34 (2.9%) clade I and 2/27 (7.4%) clade II sequences. CONCLUSIONS: Although the impact of naturally occurring NS5A RASs might be limited with upcoming pan-genotypic treatment regimens, this information is still useful to map naturally occurring HCV variants in different geographic areas in the context of current HCV therapy.