ORCID Profile
0000-0002-4624-5199
Current Organisations
Hospital Universitario La Paz
,
Universidad Internacional De La Rioja
,
Food and Drug Administration, CBER
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Publications
Combination Antiretroviral Therapy and the Risk of Myocardial Infarction
Publisher: Massachusetts Medical Society
Date: 20-11-2003
DOI: 10.1056/NEJMOA030218
Prognostic Value of Vitamin D Level for All-cause Mortality, and Association With Inflammatory Markers, in HIV-infected Persons
Publisher: Oxford University Press (OUP)
Date: 03-02-2014
Abstract: Low 25-hydroxyvitamin D (25(OH)D) has been associated with inflammation, human immunodeficiency virus (HIV) disease progression, and death. We aimed to identify the prognostic value of 25(OH)D for AIDS, non-AIDS-defining events and death, and its association with immunological/inflammatory markers. Prospective 1-1 case-control study nested within the EuroSIDA cohort. Matched cases and controls for AIDS (n = 50 matched pairs), non-AIDS-defining (n = 63) events and death (n = 41), with plasma s les during follow-up were selected. Conditional logistic regression models investigated associations between 25(OH)D levels and annual 25(OH)D change and the probability of events. Mixed models investigated relationships between 25(OH)D levels and immunological/inflammatory markers. In sum, 250 patients were included. Median time between first and last s le and last s le and event was 44.6(interquartile range [IQR]: 22.7-72.3) and 3.1(IQR: 1.4-6.4) months. Odds of death decreased by 46.0%(95% confidence interval [CI], 2.0-70.0, P = .04) for a 2-fold increase in latest 25(OH)D level. There was no association between 25(OH)D and the occurrence of AIDS or non-AIDS-defining events (P > .05). In patients with current 25(OH)D <10 ng/mL, hsIL-6 concentration increased by 4.7%(95% CI, .2,9.4, P = .04) annually after adjustment for immunological/inflammatory markers, and no change in hsCRP rate was observed (P = .76). Low Vitamin D predicts short term mortality in HIV-positive persons. Effectiveness of vitamin D supplementation on inflammation and patient outcomes should be investigated.
Opportunistic Disease and Mortality in Patients Coinfected with Hepatitis B or C Virus in the Strategic Management of Antiretroviral Therapy (SMART) Study
Publisher: Oxford University Press (OUP)
Date: 12-2008
DOI: 10.1086/593102
Abstract: In the Strategic Management of Antiretroviral Therapy (SMART) study, the risk of opportunistic disease (OD) and/or death due to any cause was elevated in the drug conservation (i.e., interrupt antiretroviral therapy until the CD4(+) cell count is 6 months and positive for HCV if they tested HCV antibody positive. The rate and hazard ratio (HR) of OD and/or death and its 2 components were compared by hepatitis status and drug conservation versus the viral suppression group. Among 5472 participants enrolled from 8 January 2002 through 11 January 2006, 930 (17%) were HBV positive and/or HCV positive. The relative risk of non-OD death in participants randomized to the drug conservation group versus the viral suppression group was comparable regardless of hepatitis status (HR for coinfected and HIV-monoinfected participants, respectively, 1.9 [95% confidence interval {CI}, 1.0-3.9 and 1.8 [95% CI, 0.9-3.4]). The rate of OD or death was 3.9 events per 100 person-years in the coinfected group and 2.0 per 100 person-years in the HIV-monoinfected group. This excess risk was due to a higher risk of non-OD death among the coinfected participants (HR, 3.6 95% CI, 2.3-5.6), whereas the risk of OD was comparable (HR, 1.1 95% CI, 0.7-1.8). The 3 leading causes of non-OD death in coinfected participants were unknown cause, substance abuse, and non-acquired immunodeficiency disease cancer. Interruption of antiretroviral therapy is particularly unsafe in persons with hepatitis virus coinfection. Although HCV- and/or HBV-coinfected participants constituted 17% of participants in the SMART study, almost one-half of all non-OD deaths occurred in this population. Viral hepatitis was an unlikely cause of this excess risk.
Deteriorating renal function and clinical outcomes in HIV-positive persons
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 13-03-2014
Using Clinical Research Networks to Assess Severity of an Emerging Influenza Pandemic
Publisher: Oxford University Press (OUP)
Date: 08-05-2018
DOI: 10.1093/CID/CIY088
Bone mineral density and inflammatory and bone biomarkers after darunavir–ritonavir combined with either raltegravir or tenofovir–emtricitabine in antiretroviral-naive adults with HIV-1: a substudy of
Publisher: Elsevier BV
Date: 11-2015
Sexual Activity Without Condoms and Risk of HIV Transmission in Serodifferent Couples When the HIV-Positive Partner Is Using Suppressive Antiretroviral Therapy
Publisher: American Medical Association (AMA)
Date: 12-07-2016
Abstract: A key factor in assessing the effectiveness and cost-effectiveness of antiretroviral therapy (ART) as a prevention strategy is the absolute risk of HIV transmission through condomless sex with suppressed HIV-1 RNA viral load for both anal and vaginal sex. To evaluate the rate of within-couple HIV transmission (heterosexual and men who have sex with men [MSM]) during periods of sex without condoms and when the HIV-positive partner had HIV-1 RNA load less than 200 copies/mL. The prospective, observational PARTNER (Partners of People on ART-A New Evaluation of the Risks) study was conducted at 75 clinical sites in 14 European countries and enrolled 1166 HIV serodifferent couples (HIV-positive partner taking suppressive ART) who reported condomless sex (September 2010 to May 2014). Eligibility criteria for inclusion of couple-years of follow-up were condomless sex and HIV-1 RNA load less than 200 copies/mL. Anonymized phylogenetic analysis compared couples' HIV-1 polymerase and envelope sequences if an HIV-negative partner became infected to determine phylogenetically linked transmissions. Condomless sexual activity with an HIV-positive partner taking virally suppressive ART. Risk of within-couple HIV transmission to the HIV-negative partner. Among 1166 enrolled couples, 888 (mean age, 42 years [IQR, 35-48] 548 heterosexual [61.7%] and 340 MSM [38.3%]) provided 1238 eligible couple-years of follow-up (median follow-up, 1.3 years [IQR, 0.8-2.0]). At baseline, couples reported condomless sex for a median of 2 years (IQR, 0.5-6.3). Condomless sex with other partners was reported by 108 HIV-negative MSM (33%) and 21 heterosexuals (4%). During follow-up, couples reported condomless sex a median of 37 times per year (IQR, 15-71), with MSM couples reporting approximately 22,000 condomless sex acts and heterosexuals approximately 36,000. Although 11 HIV-negative partners became HIV-positive (10 MSM 1 heterosexual 8 reported condomless sex with other partners), no phylogenetically linked transmissions occurred over eligible couple-years of follow-up, giving a rate of within-couple HIV transmission of zero, with an upper 95% confidence limit of 0.30/100 couple-years of follow-up. The upper 95% confidence limit for condomless anal sex was 0.71 per 100 couple-years of follow-up. Among serodifferent heterosexual and MSM couples in which the HIV-positive partner was using suppressive ART and who reported condomless sex, during median follow-up of 1.3 years per couple, there were no documented cases of within-couple HIV transmission (upper 95% confidence limit, 0.30/100 couple-years of follow-up). Additional longer-term follow-up is necessary to provide more precise estimates of risk.
Development of a definition for Rapid Progression (RP) of renal function in HIV-positive persons: the D:A:D study
Publisher: Springer Science and Business Media LLC
Date: 25-03-2014
Tuberculosis among HIV-positive patients across Europe
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 31-07-2011
Trends in underlying causes of death in people with HIV from 1999 to 2011 (D:A:D): a multicohort collaboration
Publisher: Elsevier BV
Date: 07-2014
Impact of HIV-1 Subtype and Antiretroviral Therapy on Protease and Reverse Transcriptase Genotype: Results of a Global Collaboration
Publisher: Public Library of Science (PLoS)
Date: 26-04-2005
Relationship between current level of immunodeficiency and non-acquired immunodeficiency syndrome-defining malignancies
Publisher: Wiley
Date: 26-07-2010
DOI: 10.1002/CNCR.25311
Abstract: In the combined antiretroviral therapy (cART) era, non-acquired immunodeficiency syndrome (AIDS)-defining malignancies account for more morbidity and mortality in human immunodeficiency virus-infected patients than AIDS-defining malignancies. However, conflicting data have been reported on the relationship between immunodeficiency and the development of some non-AIDS-defining malignancies. A total of 14,453 patients from the prospective, multinational EuroSIDA cohort were included. Malignancies were classified as virus-related, non-virus-related epithelial, and other. The incidence of non-AIDS-defining malignancies was calculated stratified by current CD4 count. Poisson regression was used to investigate factors associated with the development of non-AIDS-defining malignancies. A total of 356 non-AIDS-defining malignancies occurred, with an incidence rate of 4.3 per 1000 person years of follow-up (95% confidence interval [CI], 3.8-4.7) 172 (48.3%) were virus-related, 135 (37.9%) were non-virus-related epithelial, and 49 (13.7%) were classified as other. Anal (69 cases), lung (31 cases), and melanoma (13 cases), respectively, were the most common non-AIDS-defining malignancies within each group. After adjustment, current CD4 was associated with virus-related non-AIDS-defining malignancies (incidence rate ratio [IRR], 0.81 per doubling 95% CI, 0.75-0.88 P < .0001) and non-virus-related epithelial non-AIDS-defining malignancies (IRR, 0.84 95% CI, 0.75-0.95 P = .004), but not with other non-AIDS-defining malignancies (IRR, 1.04 95% CI, 0.83-1.31 P = .73). Current CD4 count was also associated with anal cancer (IRR, 0.86 95% CI, 0.75-0.99 P = .03), Hodgkin lymphoma (n = 52 IRR, 0.83 95% CI, 0.73-0.95 P = .005), and lung cancer (IRR, 0.76 95% CI, 0.64-0.90 P = .0002). A low current CD4 count was associated with an increased incidence of certain non-AIDS-defining malignancies. Starting cART earlier to reduce the proportion of patients with a low CD4 count may decrease the rate of developing many common non-AIDS-related malignancies. A randomized trial to explore this strategy is urgently needed.
Predictors of bacterial pneumonia in Evaluation of Subcutaneous Interleukin-2 in a Randomized International Trial (ESPRIT)
Publisher: Wiley
Date: 31-08-2011
Geographic and Temporal Trends in the Molecular Epidemiology and Genetic Mechanisms of Transmitted HIV-1 Drug Resistance: An Individual-Patient- and Sequence-Level Meta-Analysis
Publisher: Public Library of Science (PLoS)
Date: 07-04-2015
Short‐term weight gain after antiretroviral therapy initiation and subsequent risk of cardiovascular disease and diabetes: the D :A :D study
Publisher: Wiley
Date: 28-07-2015
DOI: 10.1111/HIV.12294
Abstract: The aim of the study was to assess the impact of the gain in body mass index (BMI) observed immediately after antiretroviral therapy (ART) initiation on the subsequent risk of cardiovascular disease (CVD) and diabetes. We analysed data from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) cohort study. Outcomes were development of (i) CVD (composite of myocardial infarction/stroke/coronary procedure) and (ii) diabetes. The main exposure variable was change in BMI from ART initiation (pre-ART) to 1 year after initiation (continuous variable) in treatment-naïve in iduals initiating ART with no history of CVD or diabetes (for respective outcomes). BMI [weight (kg)/(height (m))(2)] was categorized as underweight ( 30). Poisson regression models were fitted stratified for each pre-ART BMI category to allow for category-specific estimates of incidence rate ratio (IRR). Models were adjusted for pre-ART BMI and CD4 count, key known risk factors (time-updated where possible) and calendar year. A total of 97 CVD events occurred in 43,982 person-years (n = 9321) and 125 diabetes events in 43,278 person-years (n = 9193). In fully adjusted analyses for CVD, the IRR/unit gain in BMI (95% confidence interval) in the first year of ART, by pre-ART BMI category, was: underweight, 0.90 (0.60-1.37) normal, 1.18 (1.05-1.33) overweight, 0.87 (0.70-1.10), and obese, 0.95 (0.71-1.28) (P for interaction = 0.04). For diabetes, the IRR/unit gain in BMI was 1.11 (95% confidence interval 1.03 to 1.21), regardless of pre-ART BMI (P for interaction > 0.05). Short-term gain in BMI following ART initiation appeared to increase the longer term risk of CVD, but only in those with pre-ART BMI in the normal range. It was also associated with increased risk of diabetes regardless of pre-ART BMI.
Hepatitis C seroconversions in HIV infection across Europe: which regions and patient groups are affected?
Publisher: Wiley
Date: 29-04-2015
DOI: 10.1111/LIV.12848
Abstract: In the last decade, several outbreaks of sexually acquired acute hepatitis C (HCV) infection have been described in HIV-positive men who have sex with men (MSM). The aims of this study were to determine whether there has been an increase in the number of acute HCV infections in different parts of Europe. HCV seroconversion was defined as an HCV-antibody test change from negative to positive within the observation period in EuroSIDA. Binomial regression was performed to determine factors associated with being tested for HCV and HCV seroconversion. A total of 223 HCV seroconversions were observed from 16,188 tests [1.38% (95%CI 1.20-1.56)] among 5736 patients between 2002 and 2013. Overall the odds of acquiring HCV infection increased by 4% per year (OR 1.04 [95%CI 0.99-1.09] P = 0.10). Overall 63.2% (141/223) of all seroconversions were seen among MSM. Similar patterns were observed across all European regions (P = 0.69, test for interaction) and HIV transmission risks groups (P = 0.69, test for interaction). In multivariate analysis, North, South and East Europe had higher odds of HCV seroconversion compared with Western Europe [OR 1.90 (1.28-2.81), 1.55 (0.99-2.45) and 1.86 (1.21-2.84) P = 0.0014, P = 0.058 and P = 0.0044 respectively]. Within EuroSIDA a significant increase in HCV seroconversions can be observed after accounting for increased levels of testing for HCV in recent years. This highlights the need for increased HCV prevention efforts among HIV-positive persons in Europe.
Association Between Antiretroviral Exposure and Renal Impairment Among HIV-Positive Persons With Normal Baseline Renal Function: the D:A:D Studya
Publisher: Oxford University Press (OUP)
Date: 04-02-2013
Fatal and nonfatal AIDS and non-AIDS events in HIV-1-positive individuals with high CD4 cell counts according to viral load strata
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 28-11-2011
Increased incidence of antiretroviral drug discontinuation among patients with viremic hepatitis C virus coinfection and high hyaluronic acid, a marker of liver fibrosis
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 20-02-2014
Genome-wide mRNA and miRNA analysis of peripheral blood mononuclear cells (PBMC) reveals different miRNAs regulating HIV/HCV co-infection
Publisher: Elsevier BV
Date: 02-2014
DOI: 10.1016/J.VIROL.2013.12.026
Abstract: Co-infection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is common due to shared transmission routes. The genomic basis of HIV/HCV co-infection and its regulation by microRNA (miRNA) is unknown. Therefore, our objective was to investigate genome-wide mRNA expression and its regulation by miRNA in primary PBMCs derived from 27 patients (5 HCV - mono-infected, 5 HIV-mono-infected, 12 HCV/HIV co-infected, and 5 healthy controls). This revealed 27 miRNAs and 476 mRNAs as differentially expressed (DE) in HCV/HIV co-infection when compared to controls (adj p 50, p=4.02E-06), which may have clinical/biological implications.
Impact of chronic obstructive pulmonary disease on morbidity and mortality after myocardial infarction
Publisher: BMJ
Date: 02-2014
Development of the HIV360 international core set of outcome measures for adults living with HIV: A consensus process
Publisher: Wiley
Date: 28-12-2021
DOI: 10.1111/HIV.13221
Abstract: HIV outcomes centre primarily around clinical markers with limited focus on patient‐reported outcomes. With a global trend towards capturing the outcomes that matter most to patients, there is agreement that standardizing the definition of value in HIV care is key to their incorporation. This study aims to address the lack of routine, standardized data in HIV care. An international working group (WG) of 37 experts and patients, and a steering group (SG) of 18 experts were convened from 14 countries. The project team (PT) identified outcomes by conducting a literature review, screening 1979 articles and reviewing the full texts of 547 of these articles. Semi‐structured interviews and advisory groups were performed with the WG, SG and people living with HIV to add to the list of potentially relevant outcomes. The WG voted via a modified Delphi process – informed by six Zoom calls – to establish a core set of outcomes for use in clinical practice. From 156 identified outcomes, consensus was reached to include three patient‐reported outcomes, four clinician‐reported measures and one administratively reported outcome standardized measures were included. The WG also reached agreement to measure 22 risk‐adjustment variables. This outcome set can be applied to any person living with HIV aged 18 years. Adoption of the HIV360 outcome set will enable healthcare providers to record, compare and integrate standardized metrics across treatment sites to drive quality improvement in HIV care.
Outcomes of Influenza A(H1N1)pdm09 Virus Infection: Results from Two International Cohort Studies
Publisher: Public Library of Science (PLoS)
Date: 08-07-2014
Associations between immune depression and cardiovascular events in HIV infection
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 13-11-2013
DOI: 10.1097/01.AIDS.0000432457.91228.F3
Abstract: To consider associations between the latest/nadir CD4 cell count, and time spent with CD4 cell count less than 200 cells/μl (duration of immune depression), and myocardial infarction (MI), coronary heart disease (CHD), stroke, or cardiovascular disease (CVD) (CHD or stroke) in 33 301 HIV-positive in iduals. Longitudinal cohort study. Analyses were undertaken using Poisson regression. To investigate whether analyses of stroke were robust to the type of endpoint, we additionally included stroke-like events and rejected strokes into the stroke endpoint. Participants experienced 716 MI, 1056 CHD, 303 stroke, and 1284 CVD events. Whereas there was no evidence of a higher MI/CHD risk in those with lower latest/nadir CD4 cell counts after adjustment [current CD4 <100 cells/μl: relative rate (95% confidence interval) 0.96 (0.62-1.50) for MI, 0.89 (0.30-2.36) for CHD nadir CD4 <100 cells/μl: 1.36 (0.57-3.23) for MI, 0.98 (0.45-2.16) for CHD], stroke and CVD rates were higher in those with a latest CD4 cell count less than 100 cells/μl [2.26 (1.29-3.94) and 1.14 (0.84-1.56), respectively]. All events occurred less frequently in those who had not experienced immune depression, although evidence for a linear association with duration of immune depression was weak. The association between stroke risk and the latest CD4 cell count strengthened as stroke-like and rejected strokes were included conversely, associations with established stroke risk factors weakened. We do not find strong evidence that HIV-positive in iduals with a low CD4 cell count are more likely to experience MI/CHD. Although strokes appear to occur more commonly at low CD4 cell counts, this may be partly explained by misclassification or other biases.
Frequent hepatitis B virus rebound among HIV-hepatitis B virus-coinfected patients following antiretroviral therapy interruption
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 27-03-2010
Hyaluronic acid levels predict increased risk of non-AIDS death in hepatitis-coinfected persons interrupting antiretroviral therapy in the SMART Study
Publisher: SAGE Publications
Date: 07-2011
DOI: 10.3851/IMP1815
Abstract: In the SMART study, HIV–viral-hepatitis-coinfected persons were, compared with HIV-monoinfected persons, at higher risk of non-AIDS death if randomized to the antiretroviral therapy (ART) interruption strategy. We hypothesized that a marker of liver fibrosis, hyaluronic acid (HA), would be predictive of development of non-AIDS-related outcomes in coinfected participants in the SMART study. All participants positive for HCV RNA or hepatitis B surface antigen (HBsAg) and with stored plasma s les were included ( n=675). Plasma s les were tested for HA (normal range 0–75 ng/ml) at baseline and months 6, 12 and 24 during follow-up in the drug conservation (DC interrupt ART until CD4 + T-cell count ) group and the viral suppression (VS continued use of ART) group. Time to non-AIDS death was investigated using Kaplan–Meier analysis. Overall, 52 (31 in DC and 21 in VS) coinfected participants died during follow-up. Coinfected participants who were randomized to the DC group with baseline HA ng/ml had a cumulative risk of non-AIDS death of 24.6% after 36 months of follow-up compared with 9.3% for participants randomized to the VS group ( P=0.005), while the cumulative risk for coinfected participants with HA≤75 ng/ml was 4.1% (DC) and 4.7% (VS P=0.76). The change in HA from baseline to month 24 was 8.3 ng/ml and 4.7 ng/ml in the DC and VS group ( P=0.56), respectively. Interruption of ART was particularly unsafe in HIV–hepatitis-coinfected in iduals if plasma HA was increased. HA changed very little during follow-up and was not influenced by differences in CD4 + T-cell count or HIV viral load.
Discordances between Interpretation Algorithms for Genotypic Resistance to Protease and Reverse Transcriptase Inhibitors of Human Immunodeficiency Virus Are Subtype Dependent
Publisher: American Society for Microbiology
Date: 02-2006
DOI: 10.1128/AAC.50.2.694-701.2006
Abstract: The major limitation of drug resistance genotyping for human immunodeficiency virus remains the interpretation of the results. We evaluated the concordance in predicting therapy response between four different interpretation algorithms (Rega 6.3, HIVDB-08/04, ANRS [07/04], and VGI 8.0). Sequences were gathered through a worldwide effort to establish a database of non-B subtype sequences, and demographic and clinical information about the patients was gathered. The most concordant results were found for nonnucleoside reverse transcriptase (RT) inhibitors (93%), followed by protease inhibitors (84%) and nucleoside RT inhibitor (NRTIs) (76%). For therapy-naive patients, for nelfinavir, especially for subtypes C and G, the discordances were driven mainly by the protease (PRO) mutational pattern 82I/V + 63P + 36I/V for subtype C and 82I + 63P + 36I + 20I for subtype G. Subtype F displayed more discordances for ritonavir in untreated patients due to the combined presence of PRO 20R and 10I/V. In therapy-experienced patients, subtype G displayed a lot of discordances for saquinavir and indinavir due to mutational patterns involving PRO 90 M and 82I. Subtype F had more discordance for nelfinavir attributable to the presence of PRO 88S and 82A + 54V. For the NRTIs lamivudine and emtricitabine, CRF01_AE had more discordances than subtype B due to the presence of RT mutational patterns 65R + 115 M and 118I + 215Y, respectively. Overall, the different algorithms agreed well on the level of resistance scored, but some of the discordances could be attributed to specific (subtype-dependent) combinations of mutations. It is not yet known whether therapy response is subtype dependent, but the advice given to clinicians based on a genotypic interpretation algorithm differs according to the subtype.
Cancer Risk and Use of Protease Inhibitor or Nonnucleoside Reverse Transcriptase Inhibitor–Based Combination Antiretroviral Therapy
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 15-04-2015
Bayesian network analysis of resistance pathways against HIV-1 protease inhibitors
Publisher: Elsevier BV
Date: 06-2007
DOI: 10.1016/J.MEEGID.2006.09.004
Abstract: Interpretation of Human Immunodeficiency Virus 1 (HIV-1) genotypic drug resistance is still a major challenge in the follow-up of antiviral therapy in infected patients. Because of the high degree of HIV-1 natural variation, complex interactions and stochastic behaviour of evolution, the role of resistance mutations is in many cases not well understood. Using Bayesian network learning of HIV-1 sequence data from erse subtypes (A, B, C, F and G), we could determine the specific role of many resistance mutations against the protease inhibitors (PIs) nelfinavir (NFV), indinavir (IDV), and saquinavir (SQV). Such networks visualize relationships between treatment, selection of resistance mutations and presence of polymorphisms in a graphical way. The analysis identified 30N, 88S, and 90M for nelfinavir, 90M for saquinavir, and 82A/T and 46I/L for indinavir as most probable major resistance mutations. Moreover we found striking similarities for the role of many mutations against all of these drugs. For ex le, for all three inhibitors, we found that the novel mutation 89I was minor and associated with mutations at positions 90 and 71. Bayesian network learning provides an autonomous method to gain insight in the role of resistance mutations and the influence of HIV-1 natural variation. We successfully applied the method to three protease inhibitors. The analysis shows differences with current knowledge especially concerning resistance development in several non-B subtypes.
CD4+ T-Cell Gain With Nonnucleoside or Protease Inhibitors: Convenience May Not Always Be the Most Convenient
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2004
The Association between Serum Biomarkers and Disease Outcome in Influenza A(H1N1)pdm09 Virus Infection: Results of Two International Observational Cohort Studies
Publisher: Public Library of Science (PLoS)
Date: 27-02-2013
The Clinical Benefits of Antiretroviral Therapy in Severely Immunocompromised HIV-1-Infected Patients with and without Complete Viral Suppression
Publisher: SAGE Publications
Date: 10-2012
DOI: 10.3851/IMP2407
Abstract: The aim of this study was to determine whether there is a protective effect of combination anti-retroviral therapy (cART) on the development of clinical events in patients with ongoing severe immunosuppression. A total of 3,780 patients from the EuroSIDA study under follow-up after 2001 with a current CD4 + T-cell count ≤200 cells/mm 3 were stratified into five groups: group 1, viral load (VL) copies/ml on cART group 2, VL 50-99,999 copies/ml on cART group 3, VL 50-99,999 copies/ml off cART group 4, VL≥100,000 copies/ml on cART and group 5, VL≥100,000 copies/ml off cART. Poisson regression was used to identify the risk of (non-fatal or fatal) AIDS- and non-AIDS-related events considered together (AIDS/non-AIDS) or separately as AIDS or non-AIDS events within each group. There were 428 AIDS/non-AIDS events during 3,780 person-years of follow-up. Compared with group 1, those in group 2 had a similar incidence of AIDS/ non-AIDS events (incidence rate ratio [IRR] 1.04 95% CI 0.79–1.36). Groups 3, 4 and 5 had significantly higher incidence rates of AIDS/non-AIDS events compared with group 1 incidence rates increased from group 3 (IRR 1.78 95% CI 1.25–2.55) to group 5 (IRR 2.36 95% CI 1.66–3.40), demonstrating the increased incidence of AIDS/non-AIDS events associated with increasing viraemia. After adjustment, the use of cART was associated with a 40% reduction in the incidence of AIDS/non-AIDS events in patients with VL 50–99,999 copies/ml (IRR 0.59 95% CI 0.41–0.85) and in those with a VL ,000 copies/ml (IRR 0.66 95% CI 0.44–1.00). Similar relationships were seen for non-AIDS events and AIDS events when considered separately. In patients with ongoing severe immuno-suppression, cART was associated with significant clinical benefits in patients with suboptimal virological control or virological failure.
Variants in the ITPA Gene Protect Against Ribavirin-Induced Hemolytic Anemia in HIV/HCV-Coinfected Patients With All HCV Genotypes
Publisher: Oxford University Press (OUP)
Date: 09-12-2011
Temporal changes and regional differences in treatment uptake of hepatitis C therapy in EuroSIDA
Publisher: Wiley
Date: 19-07-2013
DOI: 10.1111/HIV.12068
Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study
Publisher: Public Library of Science (PLoS)
Date: 31-03-2015
Immunoregulatory Role of Myeloid-derived Cells in Inflammatory Bowel Disease
Publisher: Oxford University Press (OUP)
Date: 12-2015
Surveillance of illness associated with pandemic (H1N1) 2009 virus infection among adults using a global clinical site network approach: The INSIGHT FLU 002 and FLU 003 studies
Publisher: Elsevier BV
Date: 07-2011
Increased Indoleamine-2,3-Dioxygenase Activity Is Associated With Poor Clinical Outcome in Adults Hospitalized With Influenza in the INSIGHT FLU003Plus Study
Publisher: Oxford University Press (OUP)
Date: 25-10-2017
DOI: 10.1093/OFID/OFX228
Abstract: Indoleamine-2,3-dioxygenase (IDO) mediated tryptophan (TRP) depletion has antimicrobial and immuno-regulatory effects. Increased kynurenine (KYN)-to-TRP (KT) ratios, reflecting increased IDO activity, have been associated with poorer outcomes from several infections. We performed a case-control (1:2 age and sex matched) analysis of adults hospitalized with influenza A(H1N1)pdm09 with protocol-defined disease progression (died/transferred to ICU/mechanical ventilation) after enrollment (cases) or survived without progression (controls) over 60 days of follow-up. Conditional logistic regression was used to analyze the relationship between baseline KT ratio and other metabolites and disease progression. We included 32 cases and 64 controls with a median age of 52 years 41% were female, and the median durations of influenza symptoms prior to hospitalization were 8 and 6 days for cases and controls, respectively (P = .04). Median baseline KT ratios were 2-fold higher in cases (0.24 mM/M IQR, 0.13–0.40) than controls (0.12 IQR, 0.09–0.17 P ≤ .001). When ided into tertiles, 59% of cases vs 20% of controls had KT ratios in the highest tertile (0.21–0.84 mM/M). When adjusted for symptom duration, the odds ratio for disease progression for those in the highest vs lowest tertiles of KT ratio was 9.94 (95% CI, 2.25–43.90). High KT ratio was associated with poor outcome in adults hospitalized with influenza A(H1N1)pdm09. The clinical utility of this biomarker in this setting merits further exploration. NCT01056185.
Ritonavir-boosted darunavir combined with raltegravir or tenofovir–emtricitabine in antiretroviral-naive adults infected with HIV-1: 96 week results from the NEAT001/ANRS143 randomised non-inferiority
Publisher: Elsevier BV
Date: 11-2014
Increased risk of cardiovascular disease (CVD ) with age in HIV ‐positive men: a comparison of the D :A :D CVD risk equation and general population <
Publisher: Wiley
Date: 19-05-2014
DOI: 10.1111/HIV.12162
Abstract: The aim of the study was to statistically model the relative increased risk of cardiovascular disease (CVD) per year older in Data collection on Adverse events of anti-HIV Drugs (D:A:D) and to compare this with the relative increased risk of CVD per year older in general population risk equations. We analysed three endpoints: myocardial infarction (MI), coronary heart disease (CHD: MI or invasive coronary procedure) and CVD (CHD or stroke). We fitted a number of parametric age effects, adjusting for known risk factors and antiretroviral therapy (ART) use. The best-fitting age effect was determined using the Akaike information criterion. We compared the ageing effect from D:A:D with that from the general population risk equations: the Framingham Heart Study, CUORE and ASSIGN risk scores. A total of 24 323 men were included in analyses. Crude MI, CHD and CVD event rates per 1000 person-years increased from 2.29, 3.11 and 3.65 in those aged 40-45 years to 6.53, 11.91 and 15.89 in those aged 60-65 years, respectively. The best-fitting models included inverse age for MI and age + age(2) for CHD and CVD. In D:A:D there was a slowly accelerating increased risk of CHD and CVD per year older, which appeared to be only modest yet was consistently raised compared with the risk in the general population. The relative risk of MI with age was not different between D:A:D and the general population. We found only limited evidence of accelerating increased risk of CVD with age in D:A:D compared with the general population. The absolute risk of CVD associated with HIV infection remains uncertain.
Thrombocytopenia is associated with an increased risk of cancer during treated HIV disease
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 13-11-2014
A randomized placebo‐controlled trial of adefovir dipivoxil in advanced HIV infection: the ADHOC trial
Publisher: Wiley
Date: 07-2002
DOI: 10.1046/J.1468-1293.2002.00111.X
Abstract: To assess the efficacy and safety of adefovir dipivoxil (ADV) added to stable background antiretroviral therapy (ART) in HIV-infected in iduals with advanced HIV disease. ADHOC was a randomized, double-blind, placebo-controlled, international multicentre trial. Three hundred and one in iduals with CD4 cell counts < 100 cells/microL or < 200 cells/microL with nadir < 50 cells/microL were allocated to receive either 120 mg ADV (subsequently 60 mg) (n = 161) or matching placebo (n = 140) once daily. Over a median follow-up of 76 weeks, 23 (14%) and 18 (13%) participants assigned ADV and placebo, respectively, developed a new AIDS event or died (hazard ratio = 1.23, 95% confidence interval 0.66-2.29, P= 0.51). There was a lower incidence of new or recurrent herpes events in the ADV group (P = 0.009). The mean increase in CD4 cell count from baseline to week 24 was 23.0 and 24.4 cells/ micro L in ADV and placebo groups, respectively (P = 0.89), and the mean decrease in RNA was 0.32 and 0.35 log10 copies/mL at week 24 (P = 0.87) in a subset of participants. There was greater weight loss in the ADV group during the trial (P = 0.007). One hundred and twenty-four participants (41%) had stable background ART in the 8 weeks prior to and the 24 weeks after randomization. There was no significant imbalance in background ART regimens between the two treatment groups. Ninety-seven serious adverse events (SAEs) occurred, 65 and 32 in the ADV and placebo groups, respectively, with significantly shorter time to first SAE in the ADV group (P = 0.002). A total of 33 participants developed proximal renal tubular dysfunction during the trial, all but one in the ADV group. Due to the early termination of recruitment, ADHOC was unable to assess the original objective of clinical disease progression. Adding ADV to background antiretroviral therapy in advanced HIV disease did not provide immunological or virological improvement compared with placebo. Furthermore, at the doses used in this trial, ADV was associated with a significantly higher incidence of SAEs.
Sequence Analysis of In Vivo Defective Interfering-Like RNA of Influenza A H1N1 Pandemic Virus
Publisher: American Society for Microbiology
Date: 15-07-2013
DOI: 10.1128/JVI.00240-13
Abstract: Influenza virus defective interfering (DI) particles are naturally occurring noninfectious virions typically generated during in vitro serial passages in cell culture of the virus at a high multiplicity of infection. DI particles are recognized for the role they play in inhibiting viral replication and for the impact they have on the production of infectious virions. To date, influenza virus DI particles have been reported primarily as a phenomenon of cell culture and in experimentally infected embryonated chicken eggs. They have also been isolated from a respiratory infection of chickens. Using a sequencing approach, we characterize several subgenomic viral RNAs from human nasopharyngeal specimens infected with the influenza A(H1N1)pdm09 virus. The distribution of these in vivo -derived DI-like RNAs was similar to that of in vitro DIs, with the majority of the defective RNAs generated from the PB2 (segment 1) of the polymerase complex, followed by PB1 and PA. The lengths of the in vivo -derived DI-like segments also are similar to those of known in vitro DIs, and the in vivo -derived DI-like segments share internal deletions of the same segments. The presence of identical DI-like RNAs in patients linked by direct contact is compatible with transmission between them. The functional role of DI-like RNAs in natural infections remains to be established.
Related Organisations
Food And Drug Administration, CBER
Location: United States of America
Related Funding Activities
No related grants have been discovered for Vicente Soriano.