PIN44 From Randomized Controlled Trials to Real World: The Coala Study

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Incidence and Progression to Cirrhosis of New HCV infections in Persons Living with HIV.

OBJECTIVE: To estimate the incidence of HCV seroconversion and the risk of severe fibrosis/cirrhosis in HCV seroconverters among persons with HIV. METHODS: We analyzed data on 4,059 persons with HIV enrolled in a cohort study in Italy. RESULTS: Incidence rate of seroconversion was 0.6/100 person-years overall, and drug users and men-who-have-sex-with-men were at highest risk. The cumulative risk of progression to severe fibrosis/cirrhosis was 30% by 10 years after seroconversion. CONCLUSIONS: New HCV infections have a rapidly progressive course in this population. Persons with HIV and HCV superinfection should be prioritized for treatment with anti-HCV direct-acting antivirals

Risk factors associated with bacteremia in COVID-19 patients admitted to intensive care unit: a retrospective multicenter cohort study

Purpose: This multicenter observational study was done to evaluate risk factors related to the development of BSI in patients admitted to ICU for COVID-19. Methods: All patients with COVID-19 admitted in two COVID-19 dedicated ICUs in two different hospital between 02–2020 and 02–2021 were recruited. Result: 537 patients were included of whom 265 (49.3%) experienced at least one BSI. Patients who developed bacteremia had a higher SOFA score [10 (8–12) vs 9 (7–10), p < 0.001], had been intubated more frequently [95.8% vs 75%, p < 0.001] and for a median longer time [16 days (9–25) vs 8 days (5–14), p < 0.001]. Patients with BSI had a median longer ICU stay [18 days (12–31.5) vs 9 days (5–15), p < 0.001] and higher mortality [54% vs 42.3%, p < 0.001] than those who did not develop it. Development of BSI resulted in a higher SOFA score [aHR 1.08 (95% CI 1.03–1.12)] and a higher Charlson score [csAHR 1.15 (95% CI 1.05–1.25)]. Conclusion: A high SOFA score and a high Charlson score resulted associated with BSI’s development. Conversely, immunosuppressive therapy like steroids and tocilizumab, has no role in increasing the risk of bacteremia

Impact of social determinants on antiretroviral therapy access and outcomes entering the era of universal treatment for people living with HIV in Italy

Background: Social determinants are known to be a driving force of health inequalities, even in high income countries. Aim of our study was to determine if these factors can limit antiretroviral therapy (ART) access, outcome and retention in care of people living with HIV (PLHIV) in Italy. Methods: All ART naïve HIV+ patients (pts) of Italian nationality enrolled in the ICONA Cohort from 2002 to 2016 were included. The association of socio-demographic characteristics (age, sex, risk factor for HIV infection, educational level, occupational status and residency area) with time to: ART initiation (from the first positive anti-HIV test), ART regimen discontinuation, and first HIV-RNA < 50 cp/mL, were evaluated by Cox regression analysis, Kaplan Meier method and log-rank test. Results: A total of 8023 HIV+ pts (82% males, median age at first pos anti-HIV test 36 years, IQR: 29-44) were included: 6214 (77.5%) started ART during the study period. Women, people who inject drugs (PWID) and residents in Southern Italy presented the lowest levels of education and the highest rate of unemployment compared to other groups. Females, pts aged > 50 yrs., unemployed vs employed, and people with lower educational levels presented the lowest CD4 count at ART initiation compared to other groups. The overall median time to ART initiation was 0.6 years (yrs) (IQR 0.1-3.7), with a significant decrease over time [2002-2006 = 3.3 yrs. (0.2-9.4); 2007-2011 = 1.0 yrs. (0.1-3.9); 2012-2016 = 0.2 yrs. (0.1-2.1), p < 0.001]. By multivariate analysis, females (p < 0.01) and PWID (p < 0.001), presented a longer time to ART initiation, while older people (p < 0.001), people with higher educational levels (p < 0.001), unemployed (p = 0.02) and students (p < 0.001) were more likely to initiate ART. Moreover, PWID, unemployed vs stable employed, and pts. with lower educational levels showed a lower 1-year probability of achieving HIV-RNA suppression, while females, older patients, men who have sex with men (MSM), unemployed had higher 1-year risk of first-line ART discontinuation. Conclusions: Despite median time to ART start decreased from 2002 to 2016, socio-demographic factors still contribute to disparities in ART initiation, outcome and durability

Efficacy and safety of dalbavancin in the treatment of acute bacterial skin and skin structure infections (ABSSSIs) and other infections in a real-life setting: data from an Italian observational multicentric study (DALBITA study)

Objectives: We evaluated the efficacy and safety of dalbavancin in ABSSSI and ‘other sites’ infections’ (OTA). Methods: Observational study involving 11 Italian hospitals including patients that received ≥1 dose of dalbavancin in 2016–2019. The outcome was end-of-treatment efficacy and safety in ABSSSI and OTA in a real-life setting. Results: 206 patients enrolled (males 50%, median age 62 [IQR 50–76] years), 60.2% ABSSSI, 39.8% OTA. 69.7% ABSSSI vs 90.7% OTA (p = 0.003) and 46.3% ABSSSI vs 37.2% OTA (p = 0.786) received previous and concomitant antibiotics, respectively. 82.5% reached clinical cure. Eleven (5.4%) patients had non-serious adverse events (AE). OTA patients showed longer hospitalization (13.5 days, 5.5–22 vs 3, 0–11.7; p<0.0001) and received longer previous (18 days, 9–30 vs 11, 7–19; p = 0.007)/concomitant antibiotic treatments (21 days, 14–52 vs 11, 8–14; p < 0.0001), compared to ABSSSI. ABSSSI and OTA showed similar efficacy (85.5% vs 75%, p = 0.459) and safety (no AE: 81.5% vs 64.3%, p = 0.258); efficacy was independent of previous/concomitant therapies. Conclusions: Dalbavancin demonstrated a success rate of >80%, with similar efficacy/safety in ABSSSI and off-label indications. The preferential use of dalbavancin as second-line or combination therapy would seem to suggest the need for in-depth studies focused on its off-label use

Low body weight in females is a risk factor for increased tenofovir exposure and drug-related adverse events

Treatment with tenofovir sometimes leads to non-reversible kidney and/or bone diseases. Factors associated with these drug-related adverse events are poorly characterized. Our objective was to investigate such factors in patients treated long term with daily tenofovir. One-hundred Caucasian HIV-positive patients with basal creatinine clearance >80 mL/min treated with tenofovir for at least 6 months and with at least one assessment of tenofovir plasma trough concentrations were considered. Tenofovir-associated adverse events were defined as the appearance of pathological proteinuria, worsening of renal function or bone demineralization. By multivariate regression analysis, we found that serum creatinine (p\u200a=\u200a0.003) and body weight (p\u200a=\u200a0.002) were the factors independently associated with plasma tenofovir concentrations. In particular, women with body weight50 Kg (160\ub193 vs.71\ub152 ng/mL, p<0.001). High tenofovir plasma trough concentrations and the age of the patients were independently associated with the development of drug-related kidney and bone toxicity. In this retrospective study we have shown that HIV-infected women with low body weight are at risk to be exposed to high tenofovir plasma trough concentrations, ultimately resulting in a significant hazard to develop long-term tenofovir complications

Hydroxychloroquine drastically reduces immune activation in HIV-infected, antiretroviral therapy-treated immunologic nonresponders

Despite optimal suppression of HIV replication, restoration of CD4(+) T cells is not always achieved in antiretroviral therapy-treated individuals. Defective CD4 recovery in immunologic nonresponders is possibly associated with TLR-mediated immune activation driven by alterations of gut permeability. Hydroxychloroquine (HCQ) reduces endosomal TLR signaling; thus, we verified whether HCQ could dampen immune activation and be associated with an increase in CD4(+) T cells. To this end, we enrolled in a prospective study 20 HIV-infected immunologic nonresponders (CD4 count < 200 cells/mL or CD4 increase < 5% in the last 12 months) who received 400 mg/day HCQ for 6 months. HCQ had a notable impact on immune activation as shown by significant modifications of the following parameters: (1) reduced plasma lipopolysaccharide; (2) decreased TLR4-expressing CD14(+) cells, TLR4-mediated signal transduction, and mRNA synthesis; (3) reduced percentages of activated CD4(+) (CD4(+)/Ki67(+)) and CD14(+) (CD14(+)/CD69(+)) cells; (4) increased T-regulatory cells (Tregs), naive Tregs, and TLR4-expressing Tregs; (5) augmented plasmacytoid dendritic cells and reduced IFN alpha-secreting plasmacytoid dendritic cells; and (6) reduced IL-6 and TNF alpha production. HCQ-induced immune modulation was associated with increased percentages of circulating CD4(+) T cells and was mostly retained 2 months after therapy interruption. HCQ reduces lipopolysaccharide/TLR-mediated immune activation; this compound could be a useful immunomodulant in HIV-infected patients. This study is registered at EutraCT as 2009-012499-28 with study number HLS01/2009-1-16-03-2009. (Blood. 2011;118(12):3263-3272

Impact of antiretroviral dosing and daily pill burden on viral rebound rates in naive patients receiving a tenofovir-based regimen

Methods A total of 480 ART-naive patients were selected from the GNOMO cohort. Incidence rate of viral rebound (VR = first of two consecutive VL>50 cp/ml) was calculated as number of events over PYFU and expressed at univariate and multivariate analysis as incidence rate ratio (IRR). Number of both pills and doses per day were used to define three different types of regimens: twice-a-day regimens (BID regimens); once-a-day regimens with 3 pills (high-pill QD [hp-QD]). Adjusted rates of viral rebound were estimated by Poisson regression using date of first HIV-RNA <50 c/ml as baseline. Follow-up was censored at the date of VR, death, or loss to follow-up