Abstract
Background
The incidence of non-AIDS defining cancer (NADC) is higher in people living with HIV (PLWH) than in the general population, and it is already one of the leading causes of death in ...the HIV-infected population. It is estimated that the situation will be aggravated by the progressive aging of PLWH. Early diagnosis through intensive cancer screening may improve the ability for therapeutic interventions and could be critical in reducing mortality, but it might also increase expenditure and harms associated with adverse events. The aim of this study is to evaluate an enhanced screening program for early diagnosis of cancer in PLWH compared to standard practice. The specific objectives are (1) to compare the frequency of cancer diagnosed at an early stage, (2) to analyze safety of the enhanced program: adverse events and unnecessary interventions, (3) to analyze the cost-utility of the program, and (4) to estimate the overall and site-specific incidence of NADC in PLWH.
Methods
We will conduct a multicenter, non-blinded, randomized, controlled trial, comparing two parallel arms: conventional vs enhanced screening. Data will be recorded in an electronic data collection notebook. Conventional intervention group will follow the standard of care screening in the participating centers, according to the European AIDS Clinical Society recommendations, and the enhanced intervention group will follow an expanded screening aimed to early detection of lung, liver, anal, cervical, breast, prostate, colorectal, and skin cancer. The trial will be conducted within the framework of the Spanish AIDS Research Network Cohort (CoRIS).
Discussion
The trial will evaluate the efficacy, safety, and efficiency of an enhanced screening program for the early diagnosis of cancer in HIV patients compared to standard of care practice. The information provided will be relevant since there are currently no studies on expanded cancer screening strategies in patients with HIV, and available data estimating cost effectiveness or cost-utility of such as programs are scarce. An enhanced program for NADC screening in patients with HIV could lead to early diagnosis and improve the prognosis of these patients, with an acceptable rate of unnecessary interventions, but it is critical to demonstrate that the benefits clearly outweigh the harms, before the strategy could be implemented.
Trial registration
ClinicalTrials.gov
NCT04735445. Registered on 25 June 2019
Background. The pilot phase IIb VIKING study suggested that dolutegravir (DTG), a human immunodeficiency virus (HIV) integrase inhibitor (INI), would be efficacious in INI-resistant patients at the ...50 mg twice daily (BID) dose. Methods. VIKING-3 is a single-arm, open-label phase III study in which therapy-experienced adults with INI-resistant virus received DTG 50 mg BID while continuing their failing regimen (without raltegravir or elvitegravir) through day 7, after which the regimen was optimized with ≥1 fully active drug and DTG continued. The primary efficacy endpoints were the mean change from baseline in plasma HIV-1 RNA at day 8 and the proportion of subjects with HIV-1 RNA <50 c/mL at week 24. Results. Mean change in HIV-1 RNA at day 8 was -1.43 log₁₀ c/mL, and 69% of subjects achieved <50 c/mL at week 24. Multivariate analyses demonstrated a strong association between baseline DTG susceptibility and response. Response was most reduced in subjects with Q148 + ≥2 resistance-associated mutations. DTG 50 mg BID had a low (3%) discontinuation rate due to adverse events, similar to INI-naive subjects receiving DTG 50 mg once daily. Conclusions. DTG 50 mg BID-based therapy was effective in this highly treatment-experienced population with INI-resistant virus. Clinical Trials Registration. www.clinicaltrials.gov (NCT01328041) and http://www.gsk-clinicalstudywww.gsk-clinicalstudyregister.com (112574).
The characteristics of surface indium species and the transformations suffered by In–zeolite catalysts during the indium incorporation process by oxidative solid state ion exchange (OSSIE) are ...studied. This method causes a progressive dealumination of mordenite during the exchange process evidenced by
29Si MAS NMR and
27Al MAS NMR, producing a high proportion of octahedral aluminum that is further distorted at higher temperatures. However, ZSM5 is a much more stable framework for this exchange process. Exchanged indium (InO)
+ and highly-dispersed indium oxide species (In
x
O
y
) have the ability of adsorbing NO and further oxidizing it towards NO
2. Together with these dispersed species, a certain proportion of In
2O
3 crystals can be observed by XRD, which is higher for In–ZSM5. This zeolite presents a lower threshold dispersion capacity. Wider and asymmetric XPS In
3d
5/2 signals indicate the presence of two surface indium species, one of them with a similar behavior to that of bulk oxide albeit not equal, and the other strongly interacting with the zeolite. The high temperature treatment does not modify the amount of surface indium species but changes their relative proportions. The quantity of highly dispersed species is increased on In–mordenite while the opposite occurs as regards on In–ZSM5. This latter zeolite is constituted by small, packed crystals with lower superficial acidic OH groups, which could originate a higher amount of voluminous polynuclear indium cations remaining on the zeolite crystal surface during impregnation, thus provoking the higher proportion of In
2O
3 outside channels after OSSIE. Structural modifications are also observed by FTIR being higher for mordenite, such as OH depletion by solid-state exchange, dehydroxilation and creation of extra-framework Al–OH species.
Active gold catalysts for CO oxidation were obtained by the deposition–precipitation of gold on ZSM-5 and mordenite, both of them ion-exchanged with manganese. A strong promotion of Mn upon the ...activity of bimetallic Au/Mn catalysts was observed when compared with the monometallic Au–zeolites. In turn, when an in-situ reduction of the bimetallic catalysts was performed, a further increase in activity was observed. Characterizations suggested that smaller gold nanoparticles were stabilized in the bimetallic solids and that the reduction process caused a rearrangement of Au and Mn species on the catalyst surface.
•Gold nanoparticles were introduced by deposition–precipitation on Mn–zeolites.•Manganese exchanged in zeolites promotes the activity of gold-based catalysts.•A reductive treatment of bimetallic catalysts enhances the catalytic activity.•Au/Mn–mordenite catalysts showed the highest activity in CO oxidation.
There is early evidence about Valproic acid (VPA) antiviral effect. Our aim was to investigate the incidence and severity of SARS-CoV-2 infection in VPA users as compared with the general population.
...A case-control study nested within a cohort, carried out between March 1 and December 17, 2020. Retrospectively, we identified confirmed SARS-CoV-2 infection patients exposed to VPA in our health department (defined as case). We ascertained VPA regimen (all the time (AT) (292 days) or at least 20% of the study period (notAT) (≥58 days) and if VPA levels were in therapeutic range (ATR) (50–100mcg/mL) in the last 24 months. We calculated the cumulative incidence of SARS-CoV-2 infection and hospital admission in the cases, comparing it with the general unexposed VPA population (controls).
During the study period, 6183 PCR+ were detected among 281,035 inhabitants, of these, 746 were hospitalized. 691 patients were on VPA notAT and 628 (90.1%) AT. The indication for VPA use was epilepsy in 54.9%. The incidence of PCR+ was 1.736% (OR 0.785 (95%CI 0.443–1.390) and 1.910% (OR 0.865 (95%CI 0.488–1.533), on VPA notAT and VPA AT patients, respectively vs. 2.201% in people without VPA regimen. Those patients with VPA ATR had a lower risk of PCR + (OR 0.233 (95%CI 0.057–0.951) notAT; OR 0.218 (95%CI 0.053–0.890) AT). Hospital admission incidence was lower in patient on VPA (OR was 0.543 (95% CI 0.076–3.871).
Patients with VPA within the therapeutic range had a reduction of SARS-Cov-2 infection incidence greater than 75%. There is a downward trend in the risk of COVID-19 admission by SARS-CoV-2 in patients on VPA therapy. These findings warrant further investigation.
Existe evidencia preliminar sobre el efecto antiviral del ácido valproico (VPA). Nuestro objetivo fue investigar la incidencia y la gravedad de la infección por SARS-CoV-2 en usuarios de VPA, en comparación con la población general.
Estudio de casos-controles anidado en una cohorte, realizado entre el 1 de marzo y el 17 de diciembre de 2020. De forma retrospectiva identificamos en nuestro departamento de salud a las personas con infección confirmada por SARS-CoV-2, usuarias de VPA (definido como caso). Comprobamos el régimen de VPA (todo el tiempo TT, 292 días) o al menos el 20% del período de estudio (no-TT) (≥ 58 días) y si los niveles de VPA estaban en rango terapéutico (RT) (50-100 mcg/mL), en los últimos 24 meses. Calculamos la incidencia acumulada de infección por SARS-CoV-2 e ingreso en los casos, comparándola con la población general no expuesta a VPA (controles).
Durante el período de estudio se detectaron 6.183 PCR + entre 281.035 habitantes, de estos, 746 fueron hospitalizados. Seiscientos noventa y un pacientes estaban en VPA no-TT y 628 (90,1%) TT. La indicación para el uso de VPA fue la epilepsia en el 54,9%. La incidencia de PCR + fue 1.736% (odds ratio OR 0,785; intervalo de confianza IC 95% 0,443-1.390) y 1.910% (OR 0,865; IC 95% 0,488-1.533), en pacientes con VPA no-TT y VPA TT, respectivamente, vs. 2.201% en personas sin indicación de VPA. Los pacientes con VPA en RT tenían un riesgo menor de PCR + (OR 0,233; IC 95%: 0,057-0,951) no-TT; OR 0,218 (IC 95%: 0,053-0,890 TT). La incidencia de ingreso hospitalario fue menor en pacientes con VPA (OR 0,543; IC 95%: 0,076 a 3,871).
Los pacientes con VPA dentro del rango terapéutico tuvieron una reducción de la incidencia de infección por SARS-CoV-2 superior al 75%. Existe una tendencia a la baja en el riesgo de admisión por COVID-19 por SARS-CoV-2 en pacientes en terapia con VPA. Estos hallazgos justifican una mayor investigación.
Concerns have been voiced over the capacity of deintensification strategies to preserve neurocognitive function and prevent neurocognitive impairment.
We present the 96 week results of a ...neurocognitive substudy nested within the SALT clinical trial: a randomized, open-label, non-inferiority trial that compares whether atazanavir/ritonavir + lamivudine is non-inferior to atazanavir/ritonavir + two NRTIs in HIV-suppressed patients on stable triple therapy. A global deficit score (GDS) for five neurocognitive tasks was used to assess neurocognitive function. Changes in neurocognitive function (GDS value) were determined at weeks 48 and 96. The effect of atazanavir/ritonavir + lamivudine, adjusted for significant confounders, on the change in neurocognitive function was determined using analysis of covariance (ANCOVA) at week 96.
The per-protocol analysis included 92 participants (47 atazanavir/ritonavir + lamivudine and 45 atazanavir/ritonavir + two NRTIs). All baseline characteristics were comparable in both groups. At weeks 48 and 96, changes in GDS week 48, atazanavir/ritonavir + lamivudine -0.3 (95% CI -0.5 to -0.1) versus atazanavir/ritonavir + two NRTIs -0.2 (95% CI -0.4 to 0.0), P = 0.39; week 96, atazanavir/ritonavir + lamivudine -0.3 (95% CI -0.5 to -0.1) versus atazanavir/ritonavir + two NRTIs -0.2 (95% CI -0.4 to -0.1); P = 0.471 were similar. This absence of differences was also observed in all cognitive tasks. Atazanavir/ritonavir + lamivudine did not impact the change in neurocognitive function at week 96; the adjusted effect of atazanavir/ritonavir + lamivudine on GDS change, considering atazanavir/ritonavir + two NRTIs as a reference, was 0.01 (95% CI -0.18 to 0.21) (P = 0.90).
Neurocognitive function remained stable after 96 weeks, both in the atazanavir/ritonavir + lamivudine and in the atazanavir/ritonavir + two NRTIs arms, provided HIV remained suppressed.
Background
Recent and reliable estimates on the prevalence of coinfection with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) in Europe are lacking.
Aim
Leveraged on a study designed ...to assess HIV/HCV coinfection prevalence, we assessed the prevalence of HIV/HBV coinfection in Spain in 2018 and compared the results with five similar studies performed since 2002.
Methods
This cross-sectional prevalence study was carried out in 43 centres, and patients were selected using simple random sampling. The reference population comprised 40,322 patients and the sample size were 1,690 patients.
Results
The prevalence of HIV/HBV coinfection in Spain at the end of 2018 was 3.2%. The prevalence in 2002, 2009, 2015, 2016 and 2017 was 4.9%, 3.4%, 3%, 3.9% and 3%, respectively. Among the HIV/HBV-coinfected patients identified in 2018, 16.7% had cirrhosis according to transient elastography and 26.3% tested positive for antibodies against hepatitis D virus. All HIV/HBV-coinfected patients were receiving drugs with activity against HBV, and 97% of those tested for HBV DNA had an HBV DNA load < 80 IU/mL.
Conclusions
The prevalence of HIV/HBV coinfection in Spain remained stable at around 3% for a decade. Our data could facilitate the design of national programmes to control HBV infection and help identify areas of patient management that need improvement.
Three new cases of intraosseous lipoma of the os calcis were investigated, and the literature on nine previously reported cases was reviewed. Computed tomography (CT) was employed to diagnose the ...lesions preoperatively. CT energy attenuation of the lesions and fatty tissues showed similar patterns. The preoperative diagnoses suggested by clinical, anatomic, and radiologic studies were later confirmed by excision biopsy.
To analyse if a four-drug combination including two protease inhibitors (PIs) accelerates viral decay and suppression as compared with standard triple therapy in heavily immunosuppressed HIV-1 ...infected patients, an open label clinical trial was designed. PIs naive patients receiving their first highly active antiretroviral therapy were included if their CD4 cell count was lower than 200/mm3 and their HIV viral load (VL) >100,000 RNA copies/mL. Every patient received two analogues and was randomized in two groups receiving either one PI (saquinavir soft gel capsule) or two PIs (saquinavir + nelfinavir). Viral efficacy (VL <50), time to reach VL <50, viral clearance rate constant and plasmatic elimination half-life were determined. In all, 30 patients were enrolled. No viral variable was significatively improved by the four-drug combination in the short term. No clinical benefit should be expected with a four-drug (two PIs) regimen in patients with low CD4+ cell count and high VL.
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