Different patterns of HIV-1 DNA after therapy discontinuation

Background: By persisting in infected cells for a long period of time, proviral HIV-1 DNA can represent an alternative viral marker to RNA viral load during the follow-up of HIV-1 infected individuals. In the present study sequential blood samples of 10 patients under antiretroviral treatment from 1997 with two NRTIs, who refused to continue any antiviral regimen, were analyzed for 16-24 weeks to study the possible relationship between DNA and RNA viral load. Methods: The amount of proviral DNA was quantified by SYBR green real-time PCR in peripheral blood mononuclear cells from a selected group of ten patients with different levels of plasmatic viremia (RNA viral load). Results: Variable levels of proviral DNA were found without any significant correlation between proviral load and plasma HIV-1 RNA levels. Results obtained showed an increase or a rebound in viral DNA in most patients, suggesting that the absence of therapy reflects an increase and/or a persistence of cells containing viral DNA. Conclusion: Even though plasma HIV RNA levels remain the basic parameter to monitor the intensity of viral replication, the results obtained seem to indicate that DNA levels could represent an adjunct prognostic marker in monitoring HIV-1 infected subjects

Switching to nevirapine-based HAART in virologically-suppressed patients: influence of a longer twice-daily induction period on once-a-day dosing

We are conducting a multicenter, randomized, controlled, prospective, open trial to evaluate both the efficacy and toxicity of nevirapine (NVP) (given twice [BID] or once daily [QD]) in virologically-suppressed patients on a PIbased HAART. NVP BID dosing is maintained for 2 months after the switch in both groups

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

Il biofeedback preoperatorio migliora il recupero della continenza a seguito di prostatectomia radicale: una revisione sistematica con meta-analisi

BACKGROUND:&nbsp; Postoperative urinary incontinence is the overall result of urethral sphincter incompetence and modifications in urethral length after radical prostatectomy. Findings for preoperative interventions targeted at preventing post-prostatectomy incontinence include preoperative pelvic floor muscle training (PFMT) and biodfeedback (BFB), which can be managed by nurses in many countries and have been used for decades to speed up continence recovery after surgery. AIM: to determine the effectiveness of preoperative biofeedback (BFB) for post-prostatectomy urinary incontinence compared to pelvic training without BFB, considering the variability between the results of the available studies.&nbsp; METHODS: A systematic review and meta-analysis was conducted, analyzing the indications provided by the literature regarding preoperative biofeedback for preventing urinary incontinence after open radical prostatectomy, in terms of treatment regimens, timing for beginning the sessions, number of contraction and relaxation exercises, and scheduled work at home.&nbsp;Literature search on Pubmed, CINAHL, Cochrane Library, Web of Science, Scopus, EMBASE, and PEdro. RESULTS: Despite only three papers being suitable for metanalysis, our results support BFB over written instructions for continence recovery after both 3 and 6 moths from surgery. Implementing progressive programs with many different muscular exercises and including relaxation are the main recommendations. CONCLUSIONS: Preoperative biofeedback leads to improved urinary continence after 3 and 6 months from radical prostatectomy. Future studies should focus on the characteristics and number of pelvic muscle contractions required during biofeedback in order to maximize effectiveness.BACKGROUND: L'incontinenza urinaria postoperatoria è il risultato complessivo dell'incompetenza dello sfintere uretrale e delle modifiche della lunghezza dell'uretra dopo la prostatectomia radicale. I risultati degli interventi preoperatori mirati a prevenire l'incontinenza post-prostatectomia includono l'allenamento preoperatorio dei muscoli del pavimento pelvico (PFMT) e il biodfeedback (BFB), che possono essere gestiti dal personale infermieristico in molti Paesi. OBIETTIVO: determinare l'efficacia del biofeedback preoperatorio (BFB) per l'incontinenza urinaria post-prostatectomia rispetto al training pelvico senza BFB, considerando la variabilità dei risultati degli studi disponibili.&nbsp; METODI: è stata condotta una revisione sistematica con meta-analisi, analizzando le indicazioni fornite dalla letteratura sul biofeedback preoperatorio per la prevenzione dell'incontinenza urinaria in termini di regimi di trattamento, tempi di inizio delle sessioni, numero di esercizi di contrazione e rilassamento e lavoro programmato a casa. La ricerca della letteratura è stata effettuata su Pubmed, CINAHL, Cochrane Library, Web of Science, Scopus, EMBASE e PEdro. RISULTATI: nonostante solo tre articoli siano stati adatti alla metanalisi, i nostri risultati supportano il BFB rispetto alle istruzioni scritte per il recupero della continenza dopo 3 e 6 mesi dall'intervento. L'implementazione di programmi progressivi con molti esercizi muscolari diversi e l'inclusione del rilassamento sono le principali raccomandazioni. CONCLUSIONI: Il biofeedback preoperatorio porta a un miglioramento della continenza urinaria dopo 3 e 6 mesi dalla prostatectomia radicale. Gli studi futuri dovrebbero concentrarsi sulle caratteristiche e sul numero di contrazioni muscolari pelviche richieste durante il biofeedback per massimizzare l'efficacia.Il biofeedback preoperatorio migliora il recupero della continenza dopo la prostatectomia aperta: una revisione sistematica e una meta-analis

Thu0349 autologous fat grafting in the treatment of patients with systemic sclerosis: current experience and future prospects

none13nomixedSpinella, Amelia; Pignatti, Marco; Citriniti, Giorgia; Lumetti, Federica; Cocchiara, Emanuele; Palermo, Adalgisa; Sighinolfi, Gianluca; Pacchioni, Lucrezia; Zaccaria, Giovanna; Lusetti, Irene Laura; Santis, Giorgio De; Salvarani, Carlo; Giuggioli, DiliaSpinella, Amelia; Pignatti, Marco; Citriniti, Giorgia; Lumetti, Federica; Cocchiara, Emanuele; Palermo, Adalgisa; Sighinolfi, Gianluca; Pacchioni, Lucrezia; Zaccaria, Giovanna; Lusetti, Irene Laura; Santis, Giorgio De; Salvarani, Carlo; Giuggioli, Dili

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

Inflammatory effects of atazanavir/ritonavir versus darunavir/ritonavir in treatment naïve, HIV-1-infected patients

Background: Limited studies have compared the impact of different antiretroviral regimens on soluble markers of inflammation with discordant results. Methods: In this prospective study, treatment naïve HIV-1-infected patients were included if they started their current regimen with atazanavir/ritonavir (ATV/r) (N = 73, Group 1) or darunavir/ritonavir (DRV/r) (N = 85, Group 2) plus tenofovir/emtricitabine. The analysis of IL-6, MCP-1, sCD163, VCAM-1, ox-LDL, and adiponectine was performed on two stored plasma samples, the first prior to antiretroviral therapy initiation and the second one year after initiation. Results: The results of our analysis show a difference in ox-LDL between the two groups with higher mean (SD) values in ATV/r based group 608.5 ± 137.4 versus 519.1 ± 119.6 in DRV/r group, after controlling for baseline levels of ox-LDL as well as other potential confounding factors controlled by means of matching design or linear regression modelling. Conclusions: Our analysis provides further data examining the association between the modulation of vascular inflammatory and of activation markers with specific protease inhibitors-based treatments over one year of exposure to these drugs. The data show little evidence for an association, supporting the notion that antiretroviral regimens has generally poor efficiency in downregulating these soluble markers

Survival outcomes and effect of early vs. deferred cART among HIV-infected patients diagnosed at the time of an AIDS-defining event: a cohort analysis.

Objectives: We analyzed clinical progression among persons diagnosed with HIV at the time of an AIDS-defining event, and assessed the impact on outcome of timing of combined antiretroviral treatment (cART). Methods: Retrospective, European and Canadian multicohort study.. Patients were diagnosed with HIV from 1997-2004 and had clinical AIDS from 30 days before to 14 days after diagnosis. Clinical progression (new AIDS event, death) was described using Kaplan-Meier analysis stratifying by type of AIDS event. Factors associated with progression were identified with multivariable Cox regression. Progression rates were compared between those starting early (< 30 days after AIDS event) or deferred (30-270 days after AIDS event) cART. Results: The median (interquartile range) CD4 count and viral load (VL) at diagnosis of the 584 patients were 42 (16, 119) cells/ mL and 5.2 (4.5, 5.7) log 10 copies/mL. Clinical progression was observed in 165 (28.3%) patients. Older age, a higher VL at diagnosis, and a diagnosis of non-Hodgkin lymphoma (NHL) (vs. other AIDS events) were independently associated with disease progression. Of 366 patients with an opportunistic infection, 178 (48.6%) received early cART. There was no significant difference in clinical progression between those initiating cART early and those deferring treatment (adjusted hazard ratio 1.32 [95% confidence interval 0.87, 2.00], p=0.20). Conclusions: Older patients and patients with high VL or NHL at diagnosis had a worse outcome. Our data suggest that earlier initiation of cART may be beneficial among HIV-infected patients diagnosed with clinical AIDS in our setting

The association of high-sensitivity c-reactive protein and other biomarkers with cardiovascular disease in patients treated for HIV: a nested case–control study

Background: Elevated high-sensitivity C-reactive protein (hsCRP) increases the risk of cardiovascular disease (CVD) in the general population, but its role as a predictive marker in HIV-positive patients remains unclear. Aim of the study was to evaluate whether hsCRP or other biomarkers are independent predictors of CVD risk in HIV-infected patients.Methods: Retrospective, nested case-control study. HIV-positive men and women (35-69 years of age) receiving combination antiretroviral therapy (cART) were included. Cases (n = 35) had a major CVD event. Controls (n = 74) free from CVD events for at least 5 years from starting ART were matched on diabetes and smoking. HsCRP, D-dimer, P-selectin, interleukin-6 (IL-6), tissue plasminogen activator, plasminogen activator inhibitor-1 levels were measured.Results: High hsCRP was associated with CVD risk, independently of traditional cardiovascular risk factors, HIV replication and the type of ART received at the time of sampling (adjusted odds ratio 8.00 [1.23-51.94] comparing >3.3 mg/L with <0.9 mg/L; P = 0.03). Higher IL-6 and P-selectin levels were also independently associated with increased CVD risk, although the association was weaker than for hsCRP. Higher total cholesterol and lower HDL cholesterol increased CVD risk, independent of hsCRP.Conclusion: hsCRP may be a useful additional biomarker to predict CVD risk in HIV-infected patients receiving cART

Longitudinal analysis of HIV-1 coreceptor tropism by single and triplicate HIV-1 RNA and DNA sequencing in patients undergoing successful first-line antiretroviral therapy

Objectives: Maraviroc has been shown to be effective in patients harbouring CCR5-tropic HIV-1. While this CCR5 antagonist has initially been used in salvage therapy, its excellent safety profile makes it ideal for antiretroviral treatment simplification strategies in patients with suppressed plasma viraemia. The aim of this study was to compare HIV-1 tropism as detected in baseline plasma RNA and peripheral blood mononuclear cell (PBMC) DNA prior to first-line therapy and to analyse tropism evolution while on successful treatment. Methods: HIV-1 tropism was determined using triplicate genotypic testing combined with geno2pheno[coreceptor] analysis at a 10% false positive rate in 42 patients. Paired pre-treatment plasma RNA and PBMC DNA and two subsequent PBMC DNA samples (the first obtained after reaching undetectable plasma HIV-1 RNA and the second after at least 2 years of suppression of plasma viraemia) were evaluated. Results: Coreceptor tropism was completely concordant in paired pre-treatment RNA and DNA, with 26.2% of HIV-1 sequences predicted to be non-CCR5-tropic. During follow-up, coreceptor tropism switches were detected in 4 (9.5%) patients without any preferential direction. Although false positive rate discrepancies within triplicates were common, the rate of discordance of coreceptor tropism assignment among triplicate results in this mostly CCR5-tropic dataset was only 2.1%, questioning the added value of triplicate testing compared with single testing. Conclusions: HIV-1 coreceptor tropism changes during virologically successful first-line treatment are infrequent. HIV-1 DNA analysis may thus support the choice of a CCR5 antagonist in treatment switch strategies; however, maraviroc treatment outcome data are required to confirm this option