Simplified direct water footprint model to support urban water management

Water resources conservation corresponding to urban growth is an increasing challenge for European policy makers. Water footprint (WF) is one of the methods to address this challenge. The objective of this study was to develop a simplified model to assess the WF of direct domestic and non-domestic water use within an urban area and to demonstrate its effectiveness in supporting new urban water management strategies and solutions. The new model was tested on three Central European urban areas with different characteristics i.e., Wroclaw (Poland), Innsbruck (Austria), and Vicenza (Italy). Obtained WFs varied from 291 dm3/(day∙capita) in Wroclaw, 551 dm3/(day∙capita) in Vicezna to 714 dm3/(day∙capita) in Innsbruck. In addition, WF obtained with the proposed model for the city of Vicenza was compared with a more complex approach. The results proved the model to be robust in providing reasonable results using a small amount of data

In vivo effects of romidepsin on T-Cell activation, apoptosis and function in the BCN02 HIV-1 kick&Kill clinical trial

Romidepsin (RMD) is a well-characterized histone deacetylase inhibitor approved for the treatment of cutaneous T-cell lymphoma. in vitro and in vivo studies have demonstrated that it is able to induce HIV-1 gene expression in latently infected CD4+ T cells from HIV-1+ individuals on suppressive antiretroviral therapy. However, in vitro experiments suggested that RMD could also impair T-cell functionality, particularly of activated T cells. Thus, the usefulness of RMD in HIV-1 kick&kill strategies, that aim to enhance the immune system elimination of infected cells after inducing HIV-1 viral reactivation, may be limited. In order to address whether the in vitro observations are replicated in vivo, we determined the effects of RMD on the total and HIV-1-specific T-cell populations in longitudinal samples from the BCN02 kick&kill clinical trial (NCT02616874). BCN02 was a proof-of-concept study in 15 early treated HIV-1+ individuals that combined MVA.HIVconsv vaccination with three weekly infusions of RMD given as a latency reversing agent. Our results show that RMD induced a transient increase in the frequency of apoptotic T cells and an enhanced activation of vaccine-induced T cells. Although RMD reduced the number of vaccine-elicited T cells secreting multiple cytokines, viral suppressive capacity of CD8+ T cells was preserved over the RMD treatment. These observations have important implications for the design of effective kick&kill strategies for the HIV-1 cure

HIVconsv vaccines and romidepsin in early-treated HIV-1-infected individuals: safety, immunogenicity and effect on the viral reservoir (Study BCN02)

Kick&kill strategies combining drugs aiming to reactivate the viral reservoir with therapeutic vaccines to induce effective cytotoxic immune responses hold potential to achieve a functional cure for HIV-1 infection. Here, we report on an open-label, single-arm, phase I clinical trial, enrolling 15 early-treated HIV-1-infected individuals, testing the combination of the histone deacetylase inhibitor romidepsin as a latency-reversing agent and the MVA.HIVconsv vaccine. Romidepsin treatment resulted in increased histone acetylation, cell-associated HIV-1 RNA, and T-cell activation, which were associated with a marginally significant reduction of the viral reservoir. Vaccinations boosted robust and broad HIVconsv-specific T cells, which were strongly refocused toward conserved regions of the HIV-1 proteome. During a monitored ART interruption phase using plasma viral load over 2,000 copies/ml as a criterium for ART resumption, 23% of individuals showed sustained suppression of viremia up to 32 weeks without evidence for reseeding the viral reservoir. Results from this pilot study show that the combined kick&kill intervention was safe and suggest a role for this strategy in achieving an immune-driven durable viremic control.Peer ReviewedPostprint (published version

Estimation of renal function by CKD-EPI versus MDRD in a cohort of HIV-infected patients: a cross-sectional analysis.

Background Accurately determining renal function is essential for clinical management of HIV patients. Classically, it has been evaluated by estimating glomerular filtration rate (eGFR) with the MDRD-equation, but today there is evidence that the new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation has greater diagnostic accuracy. To date, however, little information exists on patients with HIV-infection. This study aimed to evaluate eGFR by CKD-EPI vs. MDRD equations and to stratify renal function according to KDIGO guidelines. Methods Cross-sectional, single center study including adult patients with HIV-infection. Results Four thousand five hundred three patients with HIV-infection (864 women; 19%) were examined. Median age was 45 years (IQR 37-52), and median baseline creatinine was 0.93 mg/dL (IQR 0.82-1.05). A similar distribution of absolute measures of eGFR was found using both formulas (p = 0.548). Baseline median eGFR was 95.2 and 90.4 mL/min/1.73 m2 for CKD-EPI and MDRD equations (p 90 mL/min/1.73 m2) in 73% patients and "mild reduced GFR" (60-89 mL/min/1.73 m2) in 24.3% of the patients, formerly classified as >60 mL/min/1.73 m2 with MDRD. Conclusions There was good correlation between CKD-EPI and MDRD. Estimating renal function using CKD-EPI equation allowed better staging of renal function and should be considered the method of choice. CKD-EPI identified a significant proportion of patients (24%) with mild reduced GFR (60-89 mL/min/1.73 m2)

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

Effect of Maraviroc intensification on HIV-1-specific T cell immunity in recently HIV-1-infected individuals

BACKGROUND: The effect of maraviroc on the maintenance and the function of HIV-1-specific T cell responses remains unknown. METHODS: Subjects recently infected with HIV-1 were randomized to receive anti-retroviral treatment with or without maraviroc intensification for 48 weeks, and were monitored up to week 60. PBMC and in vitro-expanded T cells were tested for responses to the entire HIV proteome by ELISpot analyses. Intracellular cytokine staining assays were conducted to monitor the (poly)-functionality of HIV-1-specific T cells. Analyses were performed at baseline and week 24 after treatment start, and at week 60 (3 months after maraviroc discontinuation). RESULTS: Maraviroc intensification was associated with a slower decay of virus-specific T cell responses over time compared to the non-intensified regimen in both direct ex-vivo as well as in in-vitro expanded cells. The effector function profiles of virus-specific CD8⁺ T cells were indistinguishable between the two arms and did not change over time between the groups. CONCLUSIONS: Maraviroc did not negatively impact any of the measured parameters, but was rather associated with a prolonged maintenance of HIV-1-specific T cell responses. Maraviroc, in addition to its original effect as viral entry inhibitor, may provide an additional benefit on the maintenance of virus-specific T cells which may be especially important for future viral eradication strategies

Essentials from the 2015 European AIDS Clinical Society (EACS) guidelines for the treatment of adult HIV-positive persons

BACKGROUND: The European AIDS Clinical Society (EACS) guidelines are intended for all clinicians involved in the care of HIV-positive persons, and are available in print, online, and as a free App for download for iPhone and Android. GUIDELINE HIGHLIGHTS: The 2015 version of the EACS guidelines contains major revisions in all sections; antiretroviral treatment (ART), comorbidities, coinfections and opportunistic diseases. Among the key revisions is the recommendation of ART for all HIV-positive persons, irrespectively of CD4 count, based on the Strategic Timing of AntiRetroviral Treatment (START) study results. The recommendations for the preferred and the alternative ART options have also been revised, and a new section on the use of pre-exposure prophylaxis (PrEP) has been added. A number of new antiretroviral drugs/drug combinations have been added to the updated tables on drug-drug interactions, adverse drug effects, dose adjustment for renal/liver insufficiency and for ART administration in persons with swallowing difficulties. The revisions of the coinfection section reflect the major advances in anti-hepatitis C virus (HCV) treatment with direct-acting antivirals with earlier start of treatment in individuals at increased risk of liver disease progression, and a phasing out of interferon-containing treatment regimens. The section on opportunistic diseases has been restructured according to individual pathogens/diseases and a new overview table has been added on CD4 count thresholds for different primary prophylaxes. CONCLUSIONS: The diagnosis and management of HIV infection and related coinfections, opportunistic diseases and comorbidities continue to require a multidisciplinary effort for which the 2015 version of the EACS guidelines provides an easily accessable and updated overview

Community-Acquired Pneumococcal Pneumonia in Virologically Suppressed HIV-Infected Adult Patients: A Matched Case-Control Study

Background: The study aimed to investigate whether the clinical presentations and outcomes (length of stay, ICU admission, and 30-day mortality) of pneumococcal pneumonia in virologically suppressed patients who were HIV-infected on ART with a CD4+ T-cell count > 350 cells/mm3 are comparable to those seen in patients with HIV, using a case-control design. Methods: A case-control study was carried out in Hospital Clinic, Barcelona, Spain (2001-2016). Control patients were matched by age (±10 years), sex, comorbidities, and pneumonia diagnosis in the same calendar period. Clinical presentation and outcomes of pneumococcal pneumonia in patients who were and were not infected with HIV were compared. Results: Pneumococcal pneumonia was studied in 50 cases (HIV infection) and 100 control patients (non-HIV infection). Compared with the control patients, case patients had higher rates of influenza (14% vs 2%, P = .007) and pneumococcal vaccination (10% vs 1%, P = .016). The group of cases also presented a higher rate of coinfection with hepatitis B virus (6% vs 0%, P = .036). Both groups presented similar ICU admission (18% vs 27%, P = .22), need for mechanical ventilation (12% vs 8%; P = .43), length of stay (7 days vs 7 days, P = .76), and 0% of 30-day mortality. No evidence was found of a more severe presentation or a worse clinical outcome in cases than in control patients. Conclusions: Pneumococcal pneumonia episodes requiring hospitalization in virologically suppressed patients with HIV with > 350 CD4+ T-cell count/mm3 were neither more severe nor had worse prognosis compared with uninfected patients. These results support the fact that such patients do not need treatment, admission, or care sites different to the general population

Prevalence, clinical characteristics and outcome of severe primary HIV-1 infection: a prospective cohort study

Background: Severe cases of primary HIV infection have been described in patients presenting with neurological involvement, AIDS defining events or other life-threatening events. These severe forms have not been fully studied. Objectives: To determine the prevalence and characteristics of severe PHI in a hospital-based cohort of primary HIV infection, and the response to the early initiation of antiretroviral therapy (ART) at 12 months. Methods: Every patient with PHI attending Hospital Clínic of Barcelona (1997-2015) was evaluated. Severe PHI was defined using clinical, analytical and immunological criteria. Chi-squared test was used for categorical variables and Student's t-test for quantitative variables. Results: 33% of 224 PHI patients (95% CI: 26.84%-39.16%) had a severe PHI. These patients had more symptoms, abnormal analytical parameters and hospital admissions. The severe PHI group had a significantly higher viral load although no differences were observed at 12 months in terms of viral suppression or CD4 count recovery. None died during PHI. Conclusions: Up to one third of patients in our cohort presented with a severe PHI, which was associated with higher hospitalization rates and higher plasma HIV RNA viral load. However, severe forms were not associated to a worse clinical, immunological or virological outcome at 12 months

Effect of Maraviroc Intensification on HIV-1-Specific T Cell Immunity in Recently HIV-1-Infected Individuals

Background The effect of maraviroc on the maintenance and the function of HIV-1-specific T cell responses remains unknown. Methods Subjects recently infected with HIV-1 were randomized to receive anti-retroviral treatment with or without maraviroc intensification for 48 weeks, and were monitored up to week 60. PBMC and in vitro-expanded T cells were tested for responses to the entire HIV proteome by ELISpot analyses. Intracellular cytokine staining assays were conducted to monitor the (poly)-functionality of HIV-1-specific T cells. Analyses were performed at baseline and week 24 after treatment start, and at week 60 (3 months after maraviroc discontinuation). Results Maraviroc intensification was associated with a slower decay of virus-specific T cell responses over time compared to the non-intensified regimen in both direct ex-vivo as well as in in-vitro expanded cells. The effector function profiles of virus-specific CD8+ T cells were indistinguishable between the two arms and did not change over time between the groups. Conclusions Maraviroc did not negatively impact any of the measured parameters, but was rather associated with a prolonged maintenance of HIV-1-specific T cell responses. Maraviroc, in addition to its original effect as viral entry inhibitor, may provide an additional benefit on the maintenance of virus-specific T cells which may be especially important for future viral eradication strategies