Suppression of a SARS-CoV-2 outbreak in the Italian municipality of Vo'.

On 21 February 2020, a resident of the municipality of Vo', a small town near Padua (Italy), died of pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection1. This was the first coronavirus disease 19 (COVID-19)-related death detected in Italy since the detection of SARS-CoV-2 in the Chinese city of Wuhan, Hubei province2. In response, the regional authorities imposed the lockdown of the whole municipality for 14 days3. Here we collected information on the demography, clinical presentation, hospitalization, contact network and the presence of SARS-CoV-2 infection in nasopharyngeal swabs for 85.9% and 71.5% of the population of Vo' at two consecutive time points. From the first survey, which was conducted around the time the town lockdown started, we found a prevalence of infection of 2.6% (95% confidence interval (CI): 2.1-3.3%). From the second survey, which was conducted at the end of the lockdown, we found a prevalence of 1.2% (95% CI: 0.8-1.8%). Notably, 42.5% (95% CI: 31.5-54.6%) of the confirmed SARS-CoV-2 infections detected across the two surveys were asymptomatic (that is, did not have symptoms at the time of swab testing and did not develop symptoms afterwards). The mean serial interval was 7.2 days (95% CI: 5.9-9.6). We found no statistically significant difference in the viral load of symptomatic versus asymptomatic infections (P = 0.62 and 0.74 for E and RdRp genes, respectively, exact Wilcoxon-Mann-Whitney test). This study sheds light on the frequency of asymptomatic SARS-CoV-2 infection, their infectivity (as measured by the viral load) and provides insights into its transmission dynamics and the efficacy of the implemented control measures.

Successful control measures to treat the transmission of Candida auris in Northern Italian Hospital.

Candida auris has emerged globally as a multidrug-resistant health care-associated fungal pathogen. In the literature, nosocomial outbreaks are reported worldwide. In addition, C. auris diffusion occurs in high-dependency settings with infections typically affecting critically ill patients, resulting in life-threatening disease. We describe the first documented case of C. auris in northeastern Italy and the measures applied to contain the transmission that led to zero collateral infections.

Oral and anal high-risk human papilloma virus infection in HIV-positive men who have sex with men over a 24-month longitudinal study: complexity and vaccine implications.

BACKGROUND: Few studies focused on longitudinal modifications over time of high-risk HPV (HR-HPV) at anal and oral sites in HIV+ men who have sex with men (MSM). METHODS: We described patterns and longitudinal changes of HR-HPV detection and the prevalence of HR-HPV covered by the nonavalent HPV vaccine (vax-HPV) at oral and anal sites in 165 HIV+ MSM followed in an Italian hospital. The samples were collected at baseline and after 24 months (follow-up). The presence of HPV was investigated with Inno-LiPA HPV Genotyping Extra II. RESULTS: Median age was 44 years (IQR 36-53), median CD4+ cell count at nadir was 312 cells/mm3 (IQR 187-450). A total of 120 subjects (72.7%) were receiving successful antiretroviral therapy (ART). At baseline and follow-up, the frequency of HR-HPV was significantly higher in the anal site (65.4% vs 9.4 and 62.4% vs 6.8%, respectively). Only 2.9% of subjects were persistently HR-HPV negative at both sites. All oral HR-HPV were single at baseline vs 54.6% at baseline at the anal site (p = 0.005), and all oral HR-HPV were single at follow-up vs 54.4% at anal site at follow-up (p = 0.002). The lowest rate of concordance between the oral and anal results was found for HR-HPV detection; almost all HR-HPV positive results at both anal and oral sites had different HR-HPV.The most frequent HR-HPV in anal swabs at baseline and follow-up were HPV-16 and HPV-52.At follow-up at anal site, 37.5% of patients had different HR-HPV genotypes respect to baseline, 28.8% of subjects with 1 HR-HPV at baseline had an increased number of HR-HPV, and patients on ART showed a lower frequency of confirmed anal HR-HPV detection than untreated patients (p = 0.03) over time. Additionally,54.6 and 50.5% of patients had only HR-vax-HPV at anal site at baseline and follow-up, respectively; 15.2% had only HR-vax-HPV at baseline and follow-up. CONCLUSIONS: We believe that it is important testing multiple sites over time in HIV-positive MSM. ART seems to protect men from anal HR-HPV confirmed detection. Vaccination programmes could reduce the number of HR-HPV genotypes at anal site and the risk of the first HR-HPV acquisition at the oral site.

Soluble CD163 and soluble CD14 plasma levels but not cellular HIV-DNA decrease during successful interferon-free anti-HCV therapy in HIV-1-HCV co-infected patients on effective combined anti-HIV treatment.

Soluble CD163, soluble CD14 and cellular HIV-1-DNA levels reflect two different aspects of HIV infection: immune activation and the reservoir of infected cells. The aim of this study was to describe their relationships in a cohort of HIV-HCV co-infected patients successfully treated for both HCV and HIV infections. Fifty-five patients were recruited and studied prior to the start of direct-acting antivirals (DAAs) (T0), at week 12 of DAA treatment (T1) and 24 weeks after T0 (T2). The subjects were classified as having undetectable plasma HIV viraemia (UV) or low-level viraemia (LLV) in the 18 months before T2. Plasma levels of sCD163 and of sCD14 were comparable in patients with UV and in subjects with LVL at T0, T1 and T2. The HIV DNA level was positively correlated with LLV but not with sCD163 and sCD14 levels; these two markers of inflammation were positively correlated (p = 0.017). Soluble CD163 and sCD14 decreased over time from T0 to T2 (p = 0.000 and p = 0.034, respectively). In conclusion, the significant decrease in sCD163 and sCD14 levels in patients cured of HCV infection, regardless of the presence of LLV, suggests a main role for HCV in immune activation in HIV-HCV co-infected patients.

Cytomegalovirus, Epstein-Barr virus and human herpesvirus 8 salivary shedding in HIV positive men who have sex with men with controlled and uncontrolled plasma HIV viremia: a 24-month longitudinal study.

BACKGROUND: This longitudinal study described Cytomegalovirus (CMV) DNA, Epstein-Barr (EBV) DNA and human herpesvirus 8 (HHV-8) DNA asymptomatic salivary shedding in HIV-positive men who have sex with men (MSM). We aimed to 1-analyze frequency and persistence of herpesvirus shedding, 2-correlate herpesvirus positivity and HIV viroimmunological parameters and 3-assess the association between HIV-RNA suppression and herpesvirus replication. METHODS: Herpesvirus DNA was tested with an in-house real-time PCR in 2 salivary samples obtained at T0 and T1 (24 months after T0). HIV-RNA was evaluated in the 24 months prior to T0 and in the 24 months prior to T1; MSM were classified as successfully suppressed patients (SSPs), viremic patients (VPs) and partially suppressed patients (PSPs). EBV DNA load was classified as low viral load (EBV-LVL, value ≤10,000 copies/ml) and as high viral load (EBV-HVL,> 10,000 copies/ml). Mann-Whitney U test tested the difference of the median between groups of patients. Chi-squared test and Fisher's exact test compared categorical variables according to the frequencies. Kruskal-Wallis test compared continuous data distributions between levels of categorical variables. RESULTS: Ninety-two patients (median CD4+ count 575 cells/mm3, median nadir 330 CD4+ cells/mm3) were included: 40 SSPs,33 VPs and 19 PSPs. The more frequently single virus detected was EBV, both at T0 and at T1 (in 67.5 and 70% of SSPs, in 84.8 and 81.8% of VPs and in 68.4 and 73.7% of SPSs) and the most frequently multiple positivity detected was EBV + HHV-8. At T1, the percentage of CMV positivity was higher in VPs than in SSPs (36.4% vs 5%, p < 0.001), the combined shedding of HHV-8, CMV and EBV was present only in VPs (15.1%, p = 0.01 respect to SSPs) and no VPs confirmed the absence of shedding found at T0 (vs 17.5% of SSPs, p = 0.01). EBV-HVL was more frequent in VPs than in SSPs: 78.6% at T0 (p = 0.03) and 88.9% at T1 (p = 0.01). CONCLUSIONS: The relationship between uncontrolled plasma HIV viremia and CMV, EBV, and HHV-8 shedding is multifaceted, as demonstrated by the focused association with EBV DNA load and not with its frequency and by the persistent combined detection of two oncogenic viruses as EBV and HHV-8 regardless of HIV virological control.

Structural equation modelling of viral tropism reveals its impact on achieving viral suppression within 6 months in treatment-naive HIV-1-infected patients after combination antiretroviral therapy.

OBJECTIVES: To evaluate the role of pre-treatment co-receptor tropism of plasma HIV on the achievement of viral suppression (plasma HIV RNA 1.69 log10 copies/mL) at the sixth month of combination antiretroviral therapy (cART) in a cohort of naive patients using, for the first time in this context, a path analysis (PA) approach. PATIENTS AND METHODS: Adult patients with chronic infection by subtype B HIV-1 were consecutively enrolled from the start of first-line cART (T0). Genotypic analysis of viral tropism was performed on plasma and interpreted using the bioinformatic tool Geno2pheno, with a false positive rate of 10%. A Bayesian network starting from the viro-immunological data at T0 and at the sixth month of treatment (T1) was set up and this model was evaluated using a PA approach. RESULTS: A total of 262 patients (22.1% bearing an X4 virus) were included; 178 subjects (67.9%) achieved viral suppression. A significant positive indirect effect of bearing X4 virus in plasma at T0 on log10 HIV RNA at T1 was detected (P = 0.009), the magnitude of this effect was, however, over 10-fold lower than the direct effect of log10 HIV RNA at T0 on log10 HIV RNA at T1 (P = 0.000). Moreover, a significant positive indirect effect of bearing an X4 virus on log10 HIV RNA at T0 (P = 0.003) was apparent. CONCLUSIONS: PA overcame the limitations implicit in common multiple regression analysis and showed the possible role of pre-treatment viral tropism at the recommended threshold on the outcome of plasma viraemia in naive patients after 6 months of therapy.

Time course of cellular HIV-DNA and low-level HIV viremia in HIV-HCV co-infected patients whose HCV infection had been successfully treated with directly acting antivirals.

This longitudinal study described cellular HIV-DNA changes and their correlation with HIV low-level plasma viremia (LLV) in HIV-HCV co-infected patients on successful antiretroviral and anti-HCV therapy by treatment with direct-acting antivirals (DAA). Thirty-nine patients were examined prior to the start of DAA (T0), after week 12 (T1) and 24 weeks (T2) of anti-HCV therapy. Cellular PBMC HIV-DNA was analysed as an absolute value and as the percentage of increase or decrease from T0 to T2. Patients were classified as having undetectable plasma HIV viraemia (UV) or LLV in the year before the start of anti-HCV treatment and within the T0-T2 study period. Thirty-five patients (89.7%) of the 39 subjects enrolled had the same plasma HIV viraemia control in the year before HCV treatment and in the T0-T2 interval. The HIV-DNA value at T0 and at T2 was higher in patients with LLV than in subjects with UV (p = 0.015 and p = 0.014, respectively). A similar proportion of patients with LLV and UV experienced an increase or decrease of HIV-DNA from T0 to T2. The percentage increase in HIV-DNA value (262.8%) from T0 to T2 was higher compared to the decrease (43.5%) in patients with UV (p = 0.012), and it was higher compared to the percentage increase in HIV-DNA value reported in subjects with LLV (262.8 versus 49%, p = 0.026). HIV-HCV co-infected patients experienced a multifaceted perturbation of cellular HIV-DNA levels within a 24-week period during anti-HCV treatment; the extent of the phenomenon was greater in subjects with UV. Fast HCV-RNA clearance seemed to have a greater influence on the cellular reservoir than on plasma HIV-RNA.

Epstein-Barr and cytomegalovirus DNA salivary shedding correlate with long-term plasma HIV RNA detection in HIV-infected men who have sex with men.

The aim of the study was to evaluate cytomegalovirus (CMV) and Epstein-Barr virus (EBV) DNA salivary shedding in HIV-positive men who have sex with men (MSM) and to determine whether viro-immunological parameters and long-term (24 months) plasma HIV RNA (pHIV) detection may predict herpesviruses replication. A total of 193 HIV-positive MSM were consecutively recruited (mean CD4+ cell count 607 cells/mm(3) and mean nadir value 333 cells/mm(3) ); pHIV was analyzed for 24 months prior to saliva sampling: patients were categorized as successfully suppressed (SS) and not suppressed (NS). The EBV viral load was categorized as high viral load (HVL), intermediate (IVL), or low (LVL), CMV DNA as positive or negative. NS patients experienced both herpesviruses detectability more frequently respect to SS patients (P = 0.034); conversely, no salivary shedding was more frequent in SS patients (P = 0.014). HVL EBV was more frequent in NS patients than in SS subjects (P = 0.038 for isolated EBV detection and P = 0.001 when CMV shedding was associated). NS subjects with HVL EBV had a median pHIV of 43,820 copies/ml, significantly higher respect to IVL and LVL patients (P = 0.027 and P = 0.0005, respectively). CMV shedding was mostly associated to EBV shedding. NS patients showed a significantly higher frequency of saliva HVL EBV detection compared to SS patients; moreover, NS patients with HVL EBV had a higher pHIV respect to those with IVL and LVL shedding. Our results suggest that a successful pHIV suppression could reduce the burden of salivary EBV replication and likely the risk of herpesviruses-related cancers.

Prevalence of Klebsiella pneumoniae strains producing carbapenemases and increase of resistance to colistin in an Italian teaching hospital from January 2012 To December 2014.

BACKGROUND: The aim of this study was to characterize the spread of carbapenemase-producing Klebsiella pneumoniae (CPKP) in a tertiary level hospital using ongoing active surveillance with rectal swab cultures. Furthermore, this study analyzed the presence of CPKP in the clinical samples (CS) of a single patient as well as the evolution of Colistin-sensitive strains (CoS) to Colistin-resistant strains (CoR). METHODS: This study was performed from January 1, 2012 to December 31, 2014. In 2012, a survey was conducted in the Intensive Care Department. In autumn 2013, active monitoring was extended to the Surgery Department, and since mid-2014, the surveillance has included the Medical Department as well. Only the first isolated strain from each patient was included. Antimicrobial susceptibility testing was performed on CPKP isolates: Klebsiella pneumoniae carbapenemase, oxacillinase-48, Verona integron-encoded metallo-ß-lactamase and New Delhi metallo-ß-lactamase were detected using a validated in-house PCR method, and multilocus sequence typing (MLST) was used to investigate the clonal transmission of strains. RESULTS: A total of 15,104 patients were included in the study, and 496 consecutive non-replicated strains of CPKP were collected: 149 strains were collected in 2012 (39 [26.2 %] from surveillance rectal swabs [SRS]), 133 strains were collected in 2013 (70 [52.6 %] from SRS) and 214 strains were collected in 2014 (164 [76.6 %] from SRS). We observed a significant increase in the percentage of positive SRS cases in 2014 relative to 2013 and 2012 (p = 0.0001 and p = 0.0172, respectively) and in the proportion of CPKP first isolated by SRS relative to those identified by CS (p < 0.0001). Among all available samples, the number of CoR isolated from SRS was higher in 2013 and 2014 compared with 2012 (p = 0.0019 and p = 0.008, respectively). ST-258 and ST-512 were more prevalent in the tested specimens, and a new single locus variant (SLV) of ST-512 (ST-745) was isolated. CONCLUSIONS: The results of this 3-year study of 15,104 patients highlight the clinical relevance of antimicrobial resistance as well as the drug-selection pressure of colistin therapy. The active surveillance in the three different departments increased the level of CPKP cases isolated by SRS.

Virological efficacy of abacavir: systematic review and meta-analysis.

OBJECTIVES: The efficacy of abacavir/lamivudine has been reported to be inferior to tenofovir/emtricitabine. Several randomized clinical trials (RCTs) investigated the effectiveness and safety of abacavir/lamivudine and tenofovir/emtricitabine combined antiretroviral treatment (cART) and we have reviewed the available evidence. DESIGN: Systematic review and meta-analysis of RCTs using standard Cochrane Collaboration methodologies. METHODS: We calculated risk ratios (RRs) with 95% CIs. The primary outcome was the rate of patients with viral load (VL) below the pre-defined cut-off at 48 weeks and/or at 96 weeks. Where available, results were analysed according to VL screening levels (<100,000 or >100,000 copies/mL) with conventional meta-analytical pooling by subgroups and meta-regression. RESULTS: Meta-analytical pooling of RCTs with a direct comparison of abacavir/lamivudine and tenofovir/emtricitabine according to baseline VL at 48 weeks (six trials, 4118 patients) showed that the proportions of subjects with VL <50 copies/mL were similar in the overall comparison (RR 0.98; 95% CI 0.94-1.03), in the low baseline VL strata (RR 1.01; 95% CI 0.99-1.03) and in the high baseline VL strata (RR 0.96; 95% CI 0.90-1.03). Meta-regression analysis at 48 weeks confirms the results of subgroup analysis. Similar virological results were found at 96 weeks (four trials, 2003 patients). Differences in the occurrence of adverse events requiring discontinuation of treatment favoured tenofovir recipients (RR 1.26; 95% CI 0.99-1.61), but this difference, mostly related to suspected abacavir hypersensitivity reaction, was not statistically significant. CONCLUSIONS: Our cumulative, cross-sectional data suggest a similar virological efficacy of abacavir/lamivudine and tenofovir/emtricitabine regardless of the baseline VL.

Present, old and future strategies for anti-HCV treatment in patients infected by genotype-1: estimation of the drug costs in the Calabria Region in the era of the directly acting antivirals.

BACKGROUND: In Italy, anti-HCV drugs are provided free of charge by the National Health System. Since 2011, three drug regimens including a directly acting antiviral (DAA) are considered the gold standard for HCV treatment. However, these drugs add a significant cost (roughly €26,000) to the combination of pegylated-interferon-α/ribavirin (PEG-IFN/RBV), which before DAA represented the unique treatment. To provide the National Health System potential useful information, we estimated costs to provide anti-HCV drugs to treat a population experienced for PEG-INF/RBV. METHODS: Genotype 1 HCV mono-infected or HIV/HCV co-infected individuals who were treated with PEG-IFN/RBV between 2008 and 2013 were included. The cost to treat these patients with PEG-IFN/RBV was calculated (cost 1). We also estimated costs if we had to treat these patients with a lead-in period of PEG-INF/RBV followed by PEG-IFN/RBV and a DAA in naïves (cost 2), in addition to cost 1 plus the estimated cost to re-treat with PEG-IFN/RBV and a DAA patients who had a relapse or a non response (cost 3). Moreover, all costs were normalized by SVR. Rates of foreseen response with DAA were obtained from literature data. RESULTS: The overall study population consisted of 104 patients. The rate of sustained virological response (SVR) was 55%, while it was estimated that SVR would be obtained in 75% of patients with a lead-in period with PEG-IFN/RBV followed by a DAA combination, and in 78% if this treatment is used to re-treat experienced patients with a DAA. Drug costs associated with these treatments were: €1,214,283 for cost 1, €3,474,977 for cost 2 and €3,002,095 for cost 3. Costs per SVR achieved were: €22,284 for cost 1, €44,643 for cost 2 and €38,322 for cost 3. CONCLUSIONS: Treatments including DAAs achieve a SVR in more patients than PEG-IFN/RBV but they cost around three times more than PEG-IFN/RBV alone regimens. Also, cost per SVR is almost twofold greater than PEG-IFN/RBV regimens. Therefore, it is mandatory to implement use of DAA in clinical practice, but the National Health System should allocate adequate resources to provide drugs, which challenges sustainability. Cost reduction for anti-HCV drugs should be pursued.

HCV RNA viral load is independent from CD4 cell count and plasma HIV RNA viral load in immunocompetent HIV-HCV co-infected patients: a 3-years follow-up study.

BACKGROUND: HCV RNA viral load is an important predictor of sustained virological response and, recently, a significant correlation with liver fibrosis was described. We investigated on possible influence of clinical and viro-immunological variables on HCV viral load in HIV-HCV co-infected patients over a study time of three years (2009-2012). METHODS: We retrospectively enrolled 98 adult patients with a diagnosis of chronic HIV infection in 2009, a diagnosis of chronic HCV infection with a detectable plasma HCV RNA in 2009 and 2012, HCV therapy-naïve or with failed and stopped antiviral treatment before June 2008. The following variables were recorded: age, gender, HCV genotype, IL28B rs12979860 CC genotype, HCV treatment status, advanced liver fibrosis diagnosis, antiretroviral therapy, CD4+ cell count, HCV viral load, HIV RNA (plasma HIV-1 RNA levels were measured from blood samples every three months at least). The correlation was established using linear regression analysis, analysis of variance and Fisher's exact test. Comparisons between groups were performed using Fisher's exact test, the independent samples t-test and the t-test for paired data, as appropriate, for continuous variables. A mixed mode (ME) maximum likelihood linear regression model was constructed to evaluate the dependence of HCV viral load. RESULTS: HCV RNA levels did not change significantly from 2009 to 2012 (from 3924650 ± 5320177 IU/ml to 3085128 ± 3372347 IU/ml, p = 0.13); the CD4+ count increased significantly (from a mean of 576 to a mean of 654, p = 0.003). Using linear regression, a positive correlation was observed for HCV load and genotype 1 (p = 0.002), nonresponder status (p = 0.04) and with interleukin 28B CC allele (p = 0.05). Other studied covariates failed to reach a significant correlation. CONCLUSIONS: The HCV RNA load, a known pretreatment predictor of response to antiviral therapy, was independent of the two main parameters of HIV disease, plasma HIV RNA and CD4 cell count, over an observation time of 3 years in patients with recovered or spontaneously maintained immunocompetence.

What do We Know about Cryptic Aspergillosis?

Cryptic Aspergillus species are increasingly recognized as pathogens involved in human disease. They are ubiquitarian fungi with high tenacity in their environment and can express various resistance mechanisms, often due to exposure to antifungal agents employed in agriculture and farming. The identification of such species is increasing thanks to molecular techniques, and a better description of this type of pathogen is granted. Nevertheless, the number of species and their importance in the clinical setting still need to be well studied. Furthermore, their cross-sectional involvement in animal disease, plants, and human activities requires a multidisciplinary approach involving experts from various fields. This comprehensive review aims to provide a sharp vision of the cryptic Aspergillus species, from the importance of correct identification to the better management of the infections caused by these pathogens. The review also accentuates the importance of the One Health approach for this kind of microorganism, given the interconnection between environmental exposure and aspergillosis, embracing transversely the multidisciplinary process for managing the cryptic Aspergillus species. The paper advocates the need for improving knowledge in this little-known species, given the burden of economic and health implications related to the diffusion of these bugs.

HBV in Italian Women's Jail: An Underestimated Problem?

BACKGROUND: There is little information regarding the hepatitis B virus (HBV), vaccination status, and hepatitis B exposure in Italian women's jails. We aimed to describe the HBV exposure and HBs antibody (anti-HBs) protection levels in female prisoners. MATERIAL AND METHODS: A retrospective multicentric study was performed in Italian prisons from 2021 to 2023. Univariate and multivariate analyses were conducted to identify risk factors for HBc antibody (anti-HBc) seropositivity and non-protective anti-HBs titer. RESULTS: We included 156 patients. The median age was 41.0 (IQR 34.0-48.0). Of the studied subjects, 31 (19.9%) had anti-HBc positive titer. Two women were HBsAg positive. In the multivariate analysis, older age [OR 1.06 (CI 1.01-1.11), p = 0.011], North-Eastern European [OR 11.67 (3.29-41.30), p < 0.001] and African origin [OR 6.92 (CI 1.51-31.60), p = 0.013], and drug use [OR 6.55 (CI 1.96-21.9), p = 0.002] were risk factors for HBV exposure. Thirty-seven (32%) women had no history of HBV vaccination. Forty-four (38%) had an anti-HBs non-protective titer. In the multivariate analysis, North-Eastern European origin [OR 4.55 (CI 1.19-17.50), p = 0.027] was associated with unprotective anti-HBs titer. CONCLUSION: Our results show both the low prevalence of HBV and protection in female prisoners. Age, North-Eastern European and African origin, and drug use have a role in exposure risk to HBV.

HBcAb Positivity as a Risk Factor for Missing HIV RNA Undetectability after the 3TC+DTG Switch.

Hepatitis B Core antibody (HBcAb) positivity is the surrogate marker of hepatitis B occult infection. This condition is not a contraindication for switching to two-drug (2DR) antiretroviral therapy; however, the removal of tenofovir may contribute to poor control of HBV replication. A multicentre retrospective cohort study investigated the impact of HBcAb positivity on HIV control in patients switching to a 2DR with Lamivudine and Dolutegravir (3TC-DTG). In this study, a comparison analysis was conducted between HBcAb-positive and -negative PLWH regarding HIV-RNA suppression, considering: (1): Target Not Detected (TND) < 20 cp/mL; (2) Target Detected (TD) < 20 cp/mL; and (3) Detectable > 20 cp/mL and <50 cp/mL and >50 copies/mL. A total of 267 patients on 2DR with 3TC-DTG were included. In comparison to HBcAb-negative, HBcAb-positive patients were older (45 years [35-54]) and had a lower CD4+ nadir (248 vs. 349 cells/mmc, p = 0.007). No difference in the maintenance of virological suppression was present in the two groups of patients before the switch. Although no patient had an HIV-RNA > 20 cp/mL after the switch, significantly fewer HBcAb-positive compared with -negative subjects resulted in TND at 12, 24, and 36 months after the switch: 52 (69.3%) versus 164 (85.4%), p = 0.004, 50 [72.5%] versus 143 [89.9%], p = 0.001, and 30 [66.7%] versus 90 [92.8%], p = 0.001, respectively. HBcAb positivity is associated with an increased risk of suboptimal HIV suppression during the 36 months after 3TC/DTG simplification. This finding reinforces the relevance of the OBI condition in PLWH and raises the issue of careful virological monitoring of such cases.

Patterns of Transmitted Drug Resistance Mutations and HIV-1 Subtype Dynamics in ART-Naïve Individuals in Veneto, Italy, from 2017 to 2024.

This study investigates the prevalence and patterns of transmitted drug resistance mutations (TDRMs) and HIV-1 subtypes among antiretroviral therapy (ART) naïve individuals in Veneto, Italy, from 2017 to 2024. This research aims to understand the dynamic landscape of TDRMs and HIV-1 genetic diversity to inform treatment strategies effectively. We included all adult ART-naïve people with HIV (PWH) from seven infectious disease units in Veneto, Italy. We collected the genotypic resistance testing conducted to predict drug susceptibility and subtype distribution using the Stanford HIVdb algorithm. We included 762 PWH, showing a slight but statistically significant decline in the B subtype among Italian PWH (p = 0.045) and an increase in non-B subtypes among foreigners, though it was not statistically significant (p = 0.333). The most frequent mutations were in Non-nucleoside Reverse Transcriptase Inhibitors (NNRTIs), especially in non-B subtypes, with a notable rise from 10.7% in 2017-2019 to 15.5% in 2020-2024. Notably, TDRMs were consistently detected, highlighting an ongoing challenge despite the stable prevalence observed over the years. In addition, the data revealed a concerning rise in mutations against newer drug classes, such as integrase inhibitors. Conclusively, the study underscores the necessity of continuous surveillance of HIV subtypes and resistance patterns to adapt ART regimens optimally. Despite the stable levels of drug resistance, the emergence of resistance against newer drugs necessitates ongoing vigilance and possible adjustment in treatment protocols to enhance clinical outcomes and manage HIV drug resistance effectively.

Sustained virological response and baseline predictors in HIV-HCV coinfected patients retreated with pegylated interferon and ribavirin after failing a previous interferon-based therapy: systematic review and meta-analysis.

BACKGROUND: Published data on retreatment with pegylated interferon and ribavirin of previously failing HIV-HCV coinfected patients are sparse and limited to observational study. We aimed to evaluate efficacy and pretreatment predictors. METHODS: Systematic review and meta-analysis of observational studies. The overall and genotype-related success rate was investigated. A direct comparison was performed between genotypes 1/4 and 2/3 by evaluating the sustained virological response (SVR) rate ratio (RR). The effect of study level variables on the effect size was investigated by meta-regression. Variables that were analyzed included age, gender, advanced hepatic fibrosis, pretreatment of HCV RNA and CD4, and successful antiretroviral treatment (ART). RESULTS: The available evidence was from 5 open-label, cohort studies (275 patients). The overall SVR rate was 0.280 (95% CI,0.171-0.425). The SVR rate in genotype 1/4 infections was 0.174 (95% CI, 0.129-0.230), and in genotype 2/3 infections it was 0.474 (95% CI, 0.286-0.670). The pooled RR comparing the SVR of genotype 1/4 to 2/3 was 0.369 (95% CI, 0.239-0.568), with a decreased probability of response for genotype 1/4 (P < .001). HIV RNA suppression had a significant effect on SVR (P = .005). The other covariates had no effect on the overall SVR rate. CONCLUSIONS: The overall SVR rate was 28%, consistent with the rate reported in the retreatment of mono-infected patients with the same schedule. A substantial relative reduction in the SVR rate of about one-third, when treating genotypes 1/4, was found, with a low SVR rate of 17%. Successful HIV suppression by ART predicted a higher rate of treatment success.