The predictive role of NLR and PLR for solid non-AIDS defining cancer incidence in HIV-infected subjects: a MASTER cohort study

Patients’ characteristics according to lost to follow-up at 3-years. Table S2. Distribution of non-AIDS defining cancer. Table S3. Multivariate analysis: time dependent Cox regression model. Variables included in the full model. (DOCX 20 kb

Lamivudine/dolutegravir dual therapy in HIV-infected, virologically suppressed patients

Background: Little is known about the applicability of dual treatments based on integrase inhibitors. We explored the combination of lamivudine + dolutegravir as an option when switching from standard cART in virologically suppressed patients. Methods: In this prospective cohort we enrolled patients previously switched to 3TC + DTG who were 18 years or older, with no previous resistance mutations to the used drugs, having a HIV-RNA 6 months) cART. Results: Ninety-four individuals were included. They were mostly men (77.7%) with a mean age of 53 years. They presented 159 co-morbidities including cardiovascular, bone, hepatic, kidney, and CNS diseases. Because of these pathologies, they took 207 non-ARV drugs (mean 2.2 per patient). Median duration of viral suppression was 77.5 months (IQR 61). All subjects were prospectively followed up to week 24 and all remained on dual therapy during the whole period. Neither virological failure, nor viral blip was detected. The median CD4 count rose from 658 cells/mcl (IQR 403) to 724 cells/mcl (IQR 401) (P = 0.006) without a significant (P = 0.44) change in the CD4/CD8 ratio. A significant (P < 0.0001) increment of median creatinine from 0.87 mg/dl (IQR 0.34) to 0.95 mg/dl (IQR 0.29) was observed in the first 2 months but thereafter leveled on these values (1.00 mg/dl; IQR 0.35) (P = 0.111 compared to 2 months). The lipid profile slightly improved. The daily cost of cART was significantly (P < 0.0001) reduced of 6.89 euros (SD 6.10). Discussion: Switching to a dual cART regimen based on lamivudine + dolutegravir maintains virological efficacy up to week 24, and is associated to slight improvements of the immunologic and metabolic status. The strategy allows to freely using concomitant medications for associated pathologies. The dual therapy is less expensive in economic terms. Conclusion: Although still limited evidence exists, a dolutegravir-based dual therapy in combination with lamivudine shows promising results to be confirmed in larger controlled trials

One-pill once-a-day HAART: a simplification strategy that improves adherence and quality of life of HIV-infected subjects

OBJECTIVE: The aim of the ADONE (ADherence to ONE pill) study was to verify the effect of a reduced number of pills on adherence and quality of life (QoL) in HIV-infected patients on highly active antiretroviral therapy (HAART). DESIGN: Prospective, multicenter, study. METHODS: Patients chronically treated with emtricitabine (FTC) + tenofovir (TDF) + efavirenz (EFV) or lamivudine (3TC) +TDF +EFV and with a HIV-RNA < 50 copies/mL were switched to the single-pill fixed-dose regimen (FDR) of FTC +TDF +EFV. Data were collected with SF-36 using visual analog scales. Results of the final (6 months) primary as-treated analysis are reported. RESULTS: 212 patients (77.4% males) of mean age 45.8 years were enrolled; 202 completed the study. One month post switch to FDR the adherence rate increased significantly to 96.1% from a baseline value of 93.8% (P < 0.01). The increase was steadily maintained throughout the study (96.2% at 6 months). QoL improved over time from 68.8% to 72.7% (P = 0.042) as well, and was significantly associated with the perception of health status, presence of adverse events (AEs) and number of reported AEs (P < 0.0001). QoL significantly influenced adherence (P < 0.0001). During FDR use the mean CD4 count increased from 556 to 605 cells/muL (P < 0.0001). At the end of follow-up 98% of patients maintained HIV-RNA level < 50 copies/mL and 100% <400 copies/mL. Four patients stopped therapy because they were lost to follow-up and 6 because of AEs (insomnia/nervousness 4, allergy 1, difficulties swallowing pills 1). CONCLUSION: By substituting a one-pill once-a-day HAART, we observed an improvement of both adherence and QoL while maintaining high virologic and immunologic efficacy. HAART simplicity is an added value that favors adherence and may improve long-term success

Economic Evaluation of Different Organizational Models for the Management of Patients with Hepatitis C

BACKGROUND: Access to Directly Acting Antivirals (DAAs) for Hepatitis C Virus (HCV) treatment in Italy was initially restricted to severe patients. In 2017, AIFA expanded access to all patients, to achieve elimination by 2030.AIM: To investigate the impact of different hospitals’ organizational models on elimination timing, treatment capacity and direct costs.METHODS: Most Regional healthcare systems in Italy deploy a Center of Excellence (CoE) organizational model, where patients are referred to a single major hospital in the area, which is the only one that can prescribe and deliver DAAs. The study was conducted at Bergamo’s (Lombardy, Italy) Papa Giovanni XXIII hospital (PG-23), which deploys a Hub&Spoke model: the Hub (PG-23) prescribes and delivers DAAs while Spokes (four smaller hospitals) can only prescribe them. The study compares the two models (CoE vs. H&S). Patient journey and workloads were mapped and quantified through interviews with hospital stakeholders. Cost data were collected through the hospital’s IT system; the sample comprised 2,277 HCV patients, over one year.RESULTS: The study calculated the average cost to treat HCV patients (~ € 1,470 per patient). Key cost drivers are lab tests (60%) and specialist visits (30%). Over one year, H&S can treat 68% more patients than CoE. As deferred patients absorb up to 40% of total costs, the “Optimized” model was designed by streamlining specialists’ visits and involving general practitioners during follow-up. “Optimized” model increases treatment capacity and reduces costs of deferred patients by 72% vs CoE.CONCLUSION: The study demonstrates the importance of organizational models in efficiently achieving 2030 elimination

Efficacy and safety of emtricitabine/tenofovir alafenamide (FTC/TAF) vs. emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) as a backbone for treatment of HIV-1 infection in virologically suppressed adults: subgroup analysis by third agent of a randomized, double-blind, active-controlled phase 3 trial*

Background: FTC/TAF was shown to be noninferior to FTC/TDF with advantages in markers of renal and bone safety.Objective: To evaluate the efficacy and safety of switching to FTC/TAF from FTC/TDF by third agent (boosted protease inhibitor [PI] vs. unboosted third agent).Methods: We conducted a 48-week subgroup analysis based on third agent from a randomized, double blind study in virologically suppressed adults on a FTC/TDF-containing regimen who switched to FTC/TAF vs. continued FTC/TDF while remaining on the same third agent.Results: We randomized (1:1) 663 participants to either switch to FTC/TAF (N = 333) or continue FTC/TDF (N = 330), each with baseline third agent stratifying by class of third agent in the prior treatment regimen (boosted PI 46%, unboosted third agent 54%). At week 48, significant differences in renal biomarkers and bone mineral density were observed favoring FTC/TAF over FTC/TDF (p < 0.05 for all), with similar improvements in the FTC/TAF arm in those who received boosted PI vs. unb..

The risk of late or advanced presentation of HIV infected patients is still high, associated factors evolve but impact on overall mortality is vanishing over calendar years: Results from the Italian MASTER Cohort

BACKGROUND: We aimed at evaluating frequency and factors associated with late presentation and advanced HIV disease and excess risk of death due to these conditions from 1985 to 2013 among naïve HIV infected patients enrolled in the Italian MASTER Cohort. METHODS: All antiretroviral naive adults with available CD4+ T cell count after diagnosis of HIV infection were included. Multivariable logistic regression analysis investigated factors associated either with late presentation or advanced HIV disease. Probabilities of survival were estimated both at year-1 and at year-5 according to the Kaplan-Meier method. Flexible parametric models were used to evaluate changes in risk of death overtime according to late presentation and advanced HIV disease. The analyses were stratified for calendar periods. RESULTS: 19,391 patients were included (54 % were late presenters and 37.6 % were advanced presenters). At multivariable analysis, the following factors were positively associated with late presentation: male gender (OR = 1.29), older age (≥55 years vs. <25 years; OR = 7.45), migration (OR = 1.54), and heterosexual risk factor for HIV acquisition (OR = 1.52) or IDU (OR = 1.27) compared to homosexual risk. Survival rates at year-5 increased steadily and reached 92.1 % for late presenters vs. 97.4 % for non-late presenters enrolled in the period 2004-2009. Using flexible parametric models we found a sustained reduction of hazard ratios over time for any cause deaths between late and non-late presenters over time. Similar results were found for advanced HIV disease. CONCLUSION: Screening polices need to be urgently implemented, particularly in most-at-risk categories for late presentation, such as migrants, older patients and those with heterosexual intercourse or IDU as risk factors for HIV acquisition. Although in recent years the impact of late presentation on survival decreased, about 10 % of patients diagnosed in more recent years remains at increased risk of death over a long-term follow-up

Evaluation of virological response and resistance profile in HIV-1 infected patients starting a first-line integrase inhibitor-based regimen in clinical settings

Background: Virological response and resistance profile were evaluated in drug-naïve patients starting their first-line integrase inhibitors (INIs)-based regimen in a clinical setting. Study design: Virological success (VS) and virological rebound (VR) after therapy start were assessed by survival analyses. Drug-resistance was evaluated at baseline and at virological failure. Results: Among 798 patients analysed, 38.6 %, 27.1 % and 34.3 % received raltegravir, elvitegravir and dolutegravir, respectively. Baseline resistance to NRTIs, NNRTIs, PIs and INIs was: 3.9 %, 13.9 %, 1.6 % and 0.5 %, respectively. Overall, by 12 months of treatment, the probability of VS was 95 %, while the probability of VR by 36 months after VS was 13.1 %. No significant differences in the virological response were found according to the INI used. The higher pre-therapy viremia strata was (&lt;100,000 vs. 100,000-500,000 vs. &gt; 500,000 copies/mL), lower was the probability of VS (96.0 % vs. 95.2 % vs. 91.1 %, respectively, P &lt; 0.001), and higher the probability of VR (10.2 % vs. 15.8 % vs. 16.6 %, respectively, P = 0.010). CD4 cell count &lt;200 cell/mm3 was associated with the lowest probability of VS (91.5 %, P &lt; 0.001) and the highest probability of VR (20.7 %, P = 0.008) compared to higher CD4 levels. Multivariable Cox-regression confirmed the negative role of high pre-therapy viremia and low CD4 cell count on VS, but not on VR. Forty-three (5.3 %) patients experienced VF (raltegravir: 30; elvitegravir: 9; dolutegravir: 4). Patients failing dolutegravir did not harbor any resistance mutation either in integrase or reverse transcriptase. Conclusions: Our findings confirm that patients receiving an INI-based first-line regimen achieve and maintain very high rates of VS in clinical practice

536Systematic Review and Meta-Analysis of Randomized Controlled Trials (RCTs) Comparing Initial Non-Nucleoside Reverse-Transcriptase Inhibitor (NNRTI)- versus Ritonavir Boosted Protease Inhibitor (PI/r)-based Anti-Retroviral Therapy (ART)

n/