New commercial techniques for determination of the viral load (VL) in plasma are able to detect as few as 20 copies of HIV-1 RNA/ml. The relevance of this new technical threshold is uncertain. Upon ...multivariate analysis, factors associated with detection of VLs between 20 and 49 copies/ml by the Cobas TaqMan HIV-1 v2.0 assay in an HIV clinic were the basal VL and time on antiretroviral therapy.
We sought to examine the impact of asymptomatic bacteriuria on renal transplant outcome by retrospectively analyzing 189 renal transplant recipients for whom systematic screening uncovered 298 ...episodes of asymptomatic bacteriuria in 96 recipients. These patients were treated and all were followed for 36 months. Significant risk factors included female gender, glomerulonephritis as the disease that led to transplantation, and double renal transplant. There were no differences in serum creatinine, creatinine clearance, or proteinuria between patients with and without bacteriuria. The incidence of pyelonephritis in these patients was 7.6 episodes per 100 patient-years compared with 1.07 in those without asymptomatic bacteriuria. Between two to five and more than five bacteriuria episodes were significant independent factors associated with pyelonephritis whereas more than five episodes was a significant independent factor associated with rejection. Thus, we found no differences in renal function prognosis between patients who do not develop asymptomatic bacteriuria and those uncovered by systematic screening and who received treatment following kidney transplantation. Despite this treatment, the incidence of pyelonephritis was much higher in the group of patients with detected asymptomatic bacteriuria.
The influence of acute graft pyelonephritis (AGPN) on graft outcome in renal transplant recipients still remains controversial.
We retrospectively analysed 189 patients (113 males; mean age: 49.7 ± ...13.1 years) undergoing renal transplantation at the University Hospital 12 de Octubre (Madrid, Spain) from January 2002 to December 2004, with a minimum follow-up of 36 months. Factors associated with AGPN were assessed by logistic regression analysis. Long-term graft function was compared according to the occurrence of this complication during follow-up. 'Decline in renal graft function' was defined as the increase in serum creatinine (SC) levels > 0.33 mg/dL between Month 3 and Year 1 after transplantation.
Nineteen patients (10.0%) were diagnosed with 25 episodes of AGPN (incidence rate: 4.4 episodes per 100 patient-years). The presence of glomerulonephritis as the underlying disease odds ratio (OR) 4.2; 95% confidence interval (95%CI): 1.3-14.1 and the previous occurrence of two to five (OR 9.4; 95%CI: 1.5-56.8) or more than five episodes of asymptomatic bacteriuria after transplantation (OR 19.8; 95%CI: 2.4-160.2) emerged as independent predictors for AGPN. A near-significant association was found for cytomegalovirus infection (OR 4.2; 95%CI: 0.9-18.4), whereas receiving a single-kidney transplant (vs. double-kidney) showed a protective effect (OR 0.2; 95%CI: 0.0-0.8). During the 36-month follow-up, levels of SC, creatinine clearance and 24-h proteinuria did not differ significantly between patients with or without AGPN, and this complication did not exert any effect on the risk for decline in renal graft function.
AGPN does not impair long-term graft function in renal transplant recipients.
Introduction
SARS-CoV-2 pneumonia is often associated with hyper-inflammation. The cytokine-storm-like is one of the targets of current therapies for coronavirus disease 2019 (COVID-19). High ...Interleukin-6 (IL6) blood levels have been identified in severe COVID-19 disease, but there are still uncertainties regarding the actual role of anti-IL6 antagonists in COVID-19 management. Our hypothesis was that the use of sarilumab plus corticosteroids at an early stage of the hyper-inflammatory syndrome would be beneficial and prevent progression to acute respiratory distress syndrome (ARDS).
Methods
We randomly assigned (in a 1:1 ratio) COVID-19 pneumonia hospitalized patients under standard oxygen therapy and laboratory evidence of hyper-inflammation to receive sarilumab plus usual care (experimental group) or usual care alone (control group). Corticosteroids were given to all patients at a 1 mg/kg/day of methylprednisolone for at least 3 days. The primary outcome was the proportion of patients progressing to severe respiratory failure (defined as a score in the Brescia-COVID19 scale ≥ 3) up to day 15.
Results
A total of 201 patients underwent randomization: 99 patients in the sarilumab group and 102 patients in the control group. The rate of patients progressing to severe respiratory failure (Brescia-COVID scale score ≥ 3) up to day 15 was 16.16% in the Sarilumab group versus 15.69% in the control group (RR 1.03; 95% CI 0.48–2.20). No relevant safety issues were identified.
Conclusions
In hospitalized patients with Covid-19 pneumonia, who were under standard oxygen therapy and who presented analytical inflammatory parameters, an early therapeutic intervention with sarilumab plus standard of care (including corticosteroids) was not shown to be more effective than current standard of care alone. The study was registered at EudraCT with number: 2020-002037-15.
The interaction between interferon-stimulated genes (ISGs) expression, IL28B genotypes and hepatitis C treatment outcomes has been mainly evaluated in the liver tissue from hepatitis C virus ...(HCV)-monoinfected patients but with controversial results. Herein, we examined whether more easily accessible peripheral blood mononuclear cells (PBMCs) could be used for this purpose in HIV-HCV coinfected patients, a population in whom HCV-induced liver disease progression occurs more rapidly and treatment response is lower.
Gene expression profiles were examined using the human whole genome Agilent microarray platform in PBMCs collected from HIV/HCV-coinfected patients who had completed a course of peginterferon/ribavirin therapy with validated outcomes. Patients were split out according to the achievement of sustained virological response (SVR) and IL28B rs12979860 genotypes. The GeneSpringGX software was used to select genes differentially expressed in the different groups.
Nineteen HIV/HCV-coinfected individuals receiving antiretroviral therapy and having undetectable plasma HIV-RNA were examined. Global gene expression profiles showed 42 genes differentially expressed according to treatment outcome and 56 according to IL28B genotype. Common genes were not found and functions differed for genes belonging to either group. Whereas at least 26 out of 37 repressed genes (70.3%) in SVR patients were ISGs, none of the 56 differentially expressed genes in carriers of distinct IL28B variants were ISGs (P < 0.0001).
Baseline expression of ISGs in PBMCs from HCV/HIV-coinfected patients influence the response to peginterferon/ribavirin therapy, regardless of IL28B genotypes. PBMC specimens can reliably be used for evaluating ISGs expression in clinical practice.
Tenofovir is one of the drugs of choice in first-line combinations of antiretroviral therapy. Most data on safety and efficacy in this scenario initially came from clinical trials in which tenofovir ...was combined with non-nucleoside reverse transcriptase inhibitors. Because of this, as well as the possible interaction of tenofovir with some protease inhibitors and the suspicion that this combination could increase the risk of nephrotoxicity, analysis of the clinical experience available on the combination of tenofovir (associated with emtricitabine or another nucleoside analogue) with a protease inhibitor is essential. The present review reports data on efficacy and safety, mainly from clinical trials. Taken together, these studies provide sufficient information to indicate that the combination of tenofovir and protease inhibitors is safe and effective, justifying its selection in first-line therapy or rescue therapy after virological failure.
Xenotropic murine leukemia virus-related virus (XMRV) and polytropic murine leukemia virus (MLV)-related virus are recently described human gammaretroviruses that have been associated with prostate ...cancer and chronic fatigue syndrome. These studies have been controversial because a number of laboratories have been unable to find evidence of XMRV in similar groups of patients or controls. Because the existence of XMRV raises many questions, we decided to study its presence in a group of patients infected with HIV-1 with a high proportion of intravenous drug use and coinfection by hepatitis C virus.
Forty HIV-1-infected patients under follow-up in our institution were screened for XMRV/MLV by nested polymerase chain reaction using primers targeting the gag and env region. Specific primers for mouse mitochondrial DNA were used to rule out contamination.
No evidence of XMRV or polytropic MLV-related sequences was found in any sample from patients or controls. Four samples yielded polymerase chain reaction bands whose sequence corresponded to murine endogenous retroviral sequences, however, contamination with mouse cell DNA was subsequently confirmed.
XMRV/MLV viruses do not seem to be associated with HIV-1 infection or intravenous drug use. Contamination of samples or reagents by genomic murine DNA or XMRV vectors could account for the sporadic detection of positive samples for XMRV and related agents.
The objective was to evaluate the implementation of a systematic Strongyloides stercoralis screening programme in HIV infected immigrants attending an HIV Unit in Spain. An enzyme-linked ...immunosorbent assay (ELISA) was performed to assess the presence of Strongyloides IgG. Patients with a positive serology were treated with ivermectin; serologic follow-up testing was performed. 237 patients were screened (65.4% men). Origin: 64.1 % came from Latin America, 16.5 % from Sub-Saharan Africa, 9.7 % from the Caribbean, 9.7 % from other areas. Strongyloides stercolaris IgG was positive in 13 cases (5.5 %). In the multivariate analysis, factors associated with a positive Strongyloides serology were illiteracy (OR: 23.31; p = 0.009) and eosinophilia (OR: 15.44; p > 0.0001). Nine of the 13 patients positive for S. stercoralis IgG and treated with ivermectin had a follow up serologic test: 77.8 % achieved a serologic response (55.5 % seroreversion). Screening of HIV-positive immigrants may be desirable, at least in those with higher risk of hyperinfection syndrome. Serologic testing seems a useful tool in both diagnosis and follow-up of these patients.
The number of HIV-positive immigrants have increased in Spain in the last few years, and now represent a significant proportion of the epidemic. Our objective is to describe the ...clinico-epidemiological characteristics of HIV-positive immigrants seen in a specialist unit in Madrid.
Retrospective study. Every patient born in a country other than Spain and attended an HIV Unit in Madrid between 1992 and 2009 was included.
Of the 371 patients included, 53.1% were Latin Americans, 24.5% Sub-Saharan Africans, and 22.4% others), and 60% were males. Immigrants represented 0.3% of new patients in 1992 and rose to 49.2% in 2009. The principal reason for HIV testing had been pregnancy/delivery among women (32.7%) and having a category-B disease among men (17.4%). Sexual transmission accounted for 92% of patients. Tuberculosis was the principal AIDS-diagnosing illness. Respectively 90%, 7.7%, 60%, 26.7%, 96% and 95% of patients had an IgG for HAV, HCV, Toxoplasma, Treponema, CMV and VZV. VHB-Ags+: 5.4%; PPD+: 17%. At least one syphilis episode was recorded in 62% of the men who have sex with men (MSM). Prevalence of HLA-B5701 was 6%, 0.9% and 3.8% in Caucasians, Amerindians and Afro-Americans, respectively.
Immigrants represent a significant proportion of new HIV-positive patients. It is a very heterogeneous group according to their clinical and epidemiological characteristics.
Boosted protease inhibitor monotherapy has emerged as an antiretroviral alternative option to avoid the use of nucleosides. After more than seven years of research with hundreds of patients exposed ...to this kind of therapy, controversy about its use remains. While European and Spanish guidelines for the use of antiretroviral therapy in adults include monotherapy as an alternative for simplification, experts in the USA express the view that this strategy cannot be currently recommended. Our conclusion, after more than seven years of research, is that simplification of a suppressive triple antiretroviral therapy to boosted protease inhibitor monotherapy has demonstrated safety and efficacy in a high proportion of patients. Although this is not a strategy to implement indiscriminately in all patients, it could be a good option for those patients with toxicity related to nucleoside reverse transcriptase inhibitors, or for trying to avoid such toxicities in virologically controlled patients without previous failure to protease inhibitors, restarting nucleosides if the viral load does not remain undetectable. If simplification to monotherapy is selected to treat some patients, twice-daily lopinavir/ritonavir, or preferably once-daily darunavir/ritonavir, should be chosen as data with other boosted protease inhibitors are inconclusive or even nonexistent. Nevertheless, more studies focusing on the control of HIV replication in viral reservoirs with monotherapy, as with triple therapy, are warranted.
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