RESUMEN
Background: People with HIV (PWH) are at elevated risk for atherosclerotic cardiovascular disease (ASCVD). Underrepresented racial and ethnic groups (UREGs) with HIV in the southern U.S. are disproportionately affected, yet whether cardiology specialist care for this at-risk group improves blood pressure and lipid control or prevents cardiovascular events is unknown. Methods: We evaluated a cohort of PWH from UREGs at elevated ASCVD risk without known cardiovascular disease who received HIV-related care from 2015-2018 at four academic medical centers in the Southern United States with follow up through 2020. Primary outcomes were blood pressure control (<140/90 mmHg) and lipid control (LDL-C ≤ 100 mg/dl) over 2 years and time to first major adverse cardiovascular (MACE) event. Statistical analyses were adjusted for cohort/site and patient factors including HIV measures and comorbidities. Results: Among 3972 included PWH (median age 47 years old, 32.6% female) without diagnosed cardiovascular disease, 276 (6.9%) had a cardiology clinic visit. Cardiology clinic visits were not significantly associated with subsequent blood pressure control (adjusted OR 0.78, 95% CI 0.49-1.24, p=0.29) or lipid control (adjusted OR 2.25, 95% CI 0.72-7.01, p=0.16). Over a median follow up of 5 years, patients who had a cardiology clinic visit had higher risk of MACE, overall mortality, and falsification endpoints (hospitalization or death from accident/trauma and pneumonia/sepsis) indicating a higher risk group overall, even after adjusting for measured risk factors. Conclusions: Among UREG PWH at elevated cardiovascular risk, a cardiology clinic visit was not associated with improved cardiovascular risk factors or reduced risk of cardiovascular events. Our study suggests that seeing a cardiologist is not alone sufficient to promote cardiovascular health or prevent cardiovascular events among PWH, but with low confidence given the higher risk among those who had a cardiology visit.
RESUMEN
A subset of antiretroviral therapy-treated persons with human immunodeficiency virus (HIV), referred to as immunological nonresponders (INRs), fails to normalize CD4+ T-cell numbers. In a case-control study involving 26 INRs (CD4 < 250 cells/µL) and 25 immunological responders (IRs; CD4 ≥ 250 cells/µL), we evaluated the potential contribution of transcriptionally competent defective HIV-1 proviruses to poor CD4+ T-cell recovery. Compared to the responders, the INRs had higher levels of cell-associated HIV RNA (P = .034) and higher percentages of HLA-DR+ CD4+ T cells (P < .001). While not encoding replication-competent viruses, the RNA transcripts frequently encoded HIV-1 Gag-p17 and Nef proteins. These transcripts and/or resulting proteins may activate pathway(s) leading to the immunological nonresponse phenotype.
Asunto(s)
Linfocitos T CD4-Positivos , Infecciones por VIH , VIH-1 , Provirus , Humanos , VIH-1/genética , VIH-1/inmunología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Infecciones por VIH/genética , Masculino , Estudios de Casos y Controles , Femenino , Adulto , Provirus/genética , Persona de Mediana Edad , Linfocitos T CD4-Positivos/inmunología , ARN Viral/genética , Recuento de Linfocito CD4 , Transcripción Genética , Antirretrovirales/uso terapéutico , Terapia Antirretroviral Altamente ActivaRESUMEN
BACKGROUND: Underrepresented racial and ethnic groups (UREGs) with HIV have a higher risk of cardiovascular disease (CVD) compared with the general population. Referral to a cardiovascular specialist improves CVD risk factor management in high-risk individuals. However, patient and provider factors impacting the likelihood of UREGs with HIV to have an encounter with a cardiologist are unknown. METHODS: We evaluated a cohort of UREGs with HIV and borderline CVD risk (10-year risk ≥ 5% by the pooled cohort equations or ≥ 7.5% by Framingham risk score). Participants received HIV-related care from 2014-2020 at four academic medical centers in the United States (U.S.). Adjusted Cox proportional hazards regression was used to estimate the association of patient and provider characteristics with time to first ambulatory cardiology encounter. RESULTS: A total of 2,039 people with HIV (PWH) and borderline CVD risk were identified. The median age was 45 years (IQR: 36-50); 52% were female; and 94% were Black. Of these participants, 283 (14%) had an ambulatory visit with a cardiologist (17% of women vs. 11% of men, p < .001). In fully adjusted models, older age, higher body mass index (BMI), atrial fibrillation, multimorbidity, urban residence, and no recent insurance were associated with a greater likelihood of an encounter with a cardiologist. CONCLUSION: In UREGs with HIV and borderline CVD risk, the strongest determinants of a cardiology encounter were diagnosed CVD, insurance type, and urban residence. Future research is needed to determine the extent to which these encounters impact CVD care practices and outcomes in this population. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04025125.
Asunto(s)
Infecciones por VIH , Enfermedad del Hígado Graso no Alcohólico , Humanos , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Cirrosis Hepática/patología , Hígado/patología , Infecciones por VIH/epidemiología , FibrosisRESUMEN
BACKGROUND: Food insecurity, or the lack of consistent access to nutritionally adequate and safe foods, effects up to 50% of people living with HIV (PWH) in the United States (US). PWH who are food insecure have lower antiretroviral adherence, are less likely to achieve viral suppression, and are at increased risk developing of serious illnesses, including cardiometabolic comorbidities. The objectives of this study are to better understand how food insecurity contributes to the development of cardiometabolic comorbidities among PWH and to test a novel bilingual peer navigation-mHealth intervention (weCare/Secure) designed to reduce these comorbidities in food-insecure PWH with prediabetes or Type 2 diabetes (T2DM). METHODS: In Aim 1, we will recruit a longitudinal cohort of 1800 adult (≥18 years) PWH from our clinic-based population to determine the difference in the prevalence and incidence of cardiometabolic comorbidities between food-secure and food-insecure PWH. Food insecurity screening, indicators of cardiometabolic comorbidities, and other characteristics documented in the electronic health record (EHR) will be collected annually for up to 3 years from this cohort. In Aim 2, we will conduct a randomized controlled trial among a sample of food-insecure PWH who have prediabetes or T2DM to compare changes in insulin sensitivity over 6 months between participants in weCare/Secure and participants receiving usual care. In Aim 3, we will conduct semi-structured individual in-depth interviews to explore the effect of the intervention among intervention participants with varying insulin sensitivity outcomes. TRIAL STATUS: Aim 1 (longitudinal cohort) recruitment began in May 2022 and is ongoing. Aim 2 (intervention) recruitment is planned for spring 2023 and is expected to be completed in spring 2024. Aim 3 (process evaluation) data collection will occur after sufficient completion of the 6-month assessment in Aim 2. Final results are anticipated in fall 2025. CONCLUSIONS: This research seeks to advance our understanding of how food insecurity impacts the development of cardiometabolic comorbidities among PWH and how food insecurity interventions may alleviate relevant comorbidities. Given the growing interest among health systems in addressing food insecurity, if the intervention is found to be efficacious, it could be broadly disseminated across HIV clinical care settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT04943861 . Registered on June 29, 2021.
Asunto(s)
Diabetes Mellitus Tipo 2 , Infecciones por VIH , Resistencia a la Insulina , Adulto , Humanos , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Abastecimiento de Alimentos , Inseguridad Alimentaria , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND AND OBJECTIVES: Patients who were hospitalized with coronavirus disease 2019 (COVID-19) infection are at high risk of AKI and KRT, especially in the presence of CKD. The Dapagliflozin in Respiratory Failure in Patients with COVID-19 (DARE-19) trial showed that in patients hospitalized with COVID-19, treatment with dapagliflozin versus placebo resulted in numerically fewer participants who experienced organ failure or death, although these differences were not statistically significant. We performed a secondary analysis of the DARE-19 trial to determine the efficacy and safety of dapagliflozin on kidney outcomes in the overall population and in prespecified subgroups of participants defined by baseline eGFR. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The DARE-19 trial randomized 1250 patients who were hospitalized (231 [18%] had eGFR <60 ml/min per 1.73 m2) with COVID-19 and cardiometabolic risk factors to dapagliflozin or placebo. Dual primary outcomes (time to new or worsened organ dysfunction or death, and a hierarchical composite end point of recovery [change in clinical status by day 30]), and the key secondary kidney outcome (composite of AKI, KRT, or death), and safety were assessed in participants with baseline eGFR <60 and ≥60 ml/min per 1.73 m2. RESULTS: The effect of dapagliflozin versus placebo on the primary prevention outcome (hazard ratio, 0.80; 95% confidence interval, 0.58 to 1.10), primary recovery outcome (win ratio, 1.09; 95% confidence interval, 0.97 to 1.22), and the composite kidney outcome (hazard ratio, 0.74; 95% confidence interval, 0.50 to 1.07) were consistent across eGFR subgroups (P for interaction: 0.98, 0.67, and 0.44, respectively). The effects of dapagliflozin on AKI were also similar in participants with eGFR <60 ml/min per 1.73 m2 (hazard ratio, 0.71; 95% confidence interval, 0.29 to 1.77) and ≥60 ml/min per 1.73 m2 (hazard ratio, 0.69; 95% confidence interval, 0.37 to 1.29). Dapagliflozin was well tolerated in participants with eGFR <60 and ≥60 ml/min per 1.73 m2. CONCLUSIONS: The effects of dapagliflozin on primary and secondary outcomes in hospitalized participants with COVID-19 were consistent in those with eGFR below/above 60 ml/min per 1.73 m2. Dapagliflozin was well tolerated and did not increase the risk of AKI in participants with eGFR below or above 60 ml/min per 1.73 m2.
Asunto(s)
Lesión Renal Aguda , COVID-19 , Diabetes Mellitus Tipo 2 , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , COVID-19/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Inhibidores del Cotransportador de Sodio-Glucosa 2/efectos adversos , Riñón , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/complicacionesRESUMEN
BACKGROUND: People with HIV (PWH) are at increased risk of cardiovasvular disease (CVD) and sudden cardiac death. Previous work has suggested an association between HIV infection and electrocardiographic (ECG) abnormalities. There are limited data on the burden of ECG abnormalities among PWH in a multiracial, multiethnic globally representative population. SETTING: One hundred twenty sites in the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE). METHODS: ECG findings were grouped into clinically relevant categories using sex-specific thresholds when indicated. We used the Fisher exact tests to assess associations of demographic characteristics and ECG abnormalities. We used logistic regression model to assess associations between demographic and HIV management measures, with adjustment. RESULTS: We analyzed data for 7720 PWH (99% of participants) (median age 50 years, 69% male participants). There were 3346 (43%) Black or African American, 2680 (35%) White, and 1139 (15%) Asian participants. Most of the participants (97%) had viral load that was <400 copies/mL or
Asunto(s)
Infecciones por VIH , Adulto , Negro o Afroamericano , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Grupos Raciales , Carga ViralRESUMEN
Importance: Based on contemporary estimates in the US, evidence-based therapies for cardiovascular risk reduction are generally underused among patients with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD). Objective: To determine the use of evidence-based cardiovascular preventive therapies in a broad US population with diabetes and ASCVD. Design, Setting, and Participants: This multicenter cohort study used health system-level aggregated data within the National Patient-Centered Clinical Research Network, including 12 health systems. Participants included patients with diabetes and established ASCVD (ie, coronary artery disease, cerebrovascular disease, and peripheral artery disease) between January 1 and December 31, 2018. Data were analyzed from September 2020 until January 2021. Exposures: One or more health care encounters in 2018. Main Outcomes and Measures: Patient characteristics by prescription of any of the following key evidence-based therapies: high-intensity statin, angiotensin-converting enzyme inhibitor (ACEI) or angiotensin-receptor blocker (ARB) and sodium glucose cotransporter-2 inhibitors (SGLT2I) or glucagon-like peptide-1 receptor agonist (GLP-1RA). Results: The overall cohort included 324â¯706 patients, with a mean (SD) age of 68.1 (12.2) years and 144â¯169 (44.4%) women and 180â¯537 (55.6%) men. A total of 59â¯124 patients (18.2% ) were Black, and 41â¯470 patients (12.8%) were Latinx. Among 205â¯885 patients with specialized visit data from the prior year, 17â¯971 patients (8.7%) visited an endocrinologist, 54â¯330 patients (26.4%) visited a cardiologist, and 154â¯078 patients (74.8%) visited a primary care physician. Overall, 190â¯277 patients (58.6%) were prescribed a statin, but only 88â¯426 patients (26.8%) were prescribed a high-intensity statin; 147â¯762 patients (45.5%) were prescribed an ACEI or ARB, 12â¯724 patients (3.9%) were prescribed a GLP-1RA, and 8989 patients (2.8%) were prescribed an SGLT2I. Overall, 14â¯918 patients (4.6%) were prescribed all 3 classes of therapies, and 138â¯173 patients (42.6%) were prescribed none. Patients who were prescribed a high-intensity statin were more likely to be men (59.9% [95% CI, 59.6%-60.3%] of patients vs 55.6% [95% CI, 55.4%-55.8%] of patients), have coronary atherosclerotic disease (79.9% [95% CI, 79.7%-80.2%] of patients vs 73.0% [95% CI, 72.8%-73.3%] of patients) and more likely to have seen a cardiologist (40.0% [95% CI, 39.6%-40.4%] of patients vs 26.4% [95% CI, 26.2%-26.6%] of patients). Conclusions and Relevance: In this large cohort of US patients with diabetes and ASCVD, fewer than 1 in 20 patients were prescribed all 3 evidence-based therapies, defined as a high-intensity statin, either an ACEI or ARB, and either an SGLT2I and/or a GLP-1RA. These findings suggest that multifaceted interventions are needed to overcome barriers to the implementation of evidence-based therapies and facilitate their optimal use.
Asunto(s)
Antihipertensivos/uso terapéutico , Aterosclerosis , Diabetes Mellitus Tipo 2 , Hipoglucemiantes/uso terapéutico , Hipolipemiantes/uso terapéutico , Anciano , Anciano de 80 o más Años , Aterosclerosis/complicaciones , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/epidemiología , Estudios de Cohortes , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estados UnidosRESUMEN
BACKGROUND: Tocilizumab, an interleukin 6 receptor (IL-6R) antagonist monoclonal antibody, has shown efficacy in patients with coronavirus disease 2019 (COVID-19) pneumonia, but the optimal dose is unknown. METHODS: Patients hospitalized for moderate to severe COVID-19 pneumonia were randomized 1:1 to receive standard of care treatment and 1-2 doses of intravenous tocilizumab 4 mg/kg or 8 mg/kg (open-label). Primary pharmacokinetic and pharmacodynamic end points were serum concentrations of tocilizumab and soluble interleukin 6 receptor (sIL-6R), IL-6, ferritin, and C-reactive protein (CRP), from baseline to day 60. The secondary end point was safety. Key exploratory efficacy end points included clinical status, time to discharge, mortality rate, and incidence of mechanical ventilation. RESULTS: Of 100 patients randomized, 49 received tocilizumab 4 mg/kg and 48 received 8 mg/kg. In pharmacokinetic and sIL-6R assessments, dose-dependent differences were seen in patients who received 1 or 2 doses of 4 or 8 mg/kg. Serum concentrations of IL-6, ferritin, and CRP and safety outcomes were comparable between groups. Through day 60, serious adverse events were reported in 30.6% and 25.0% of patients in the 4- and 8-mg/kg groups, respectively. Eight patients (16.3%) in the 4-mg/kg group and 6 (12.5%) in the 8-mg/kg group died. Exploratory time-to-event outcomes favored 8 mg/kg within the first 2 weeks. CONCLUSIONS: In patients with moderate to severe COVID-19 pneumonia who received tocilizumab 4 or 8 mg/kg, pharmacokinetic and sIL-6R assessments showed expected dose-dependent effects; pharmacodynamic assessments and safety were comparable, with no new safety signals. Further study is required before a lower dose of tocilizumab can be recommended in patients with COVID-19 pneumonia. CLINICAL TRIALS REGISTRATION: NCT04363736.
RESUMEN
BACKGROUND: Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infectious virus isolation in outpatients with coronavirus disease 2019 (COVID-19) has been associated with viral RNA levels and symptom duration, little is known about the host, disease, and viral determinants of infectious virus detection. METHODS: COVID-19 adult outpatients were enrolled within 7 days of symptom onset. Clinical symptoms were recorded via patient diary. Nasopharyngeal swabs were collected to quantitate SARS-CoV-2 RNA by reverse transcriptase polymerase chain reaction and for infectious virus isolation in Vero E6-cells. SARS-CoV-2 antibodies were measured in serum using a validated ELISA assay. RESULTS: Among 204 participants with mild-to-moderate symptomatic COVID-19, the median nasopharyngeal viral RNA was 6.5 (interquartile range [IQR] 4.7-7.6 log10 copies/mL), and 26% had detectable SARS-CoV-2 antibodies (immunoglobulin (Ig)A, IgM, IgG, and/or total Ig) at baseline. Infectious virus was recovered in 7% of participants with SARS-CoV-2 antibodies compared to 58% of participants without antibodies (prevalence ratio [PR] = 0.12, 95% confidence interval [CI]: .04, .36; P = .00016). Infectious virus isolation was also associated with higher levels of viral RNA (mean RNA difference +2.6 log10, 95% CI: 2.2, 3.0; P < .0001) and fewer days since symptom onset (PR = 0.79, 95% CI: .71, .88 per day; P < .0001). CONCLUSIONS: The presence of SARS-CoV-2 antibodies is strongly associated with clearance of infectious virus. Seropositivity and viral RNA levels are likely more reliable markers of infectious virus clearance than subjective measure of COVID-19 symptom duration. Virus-targeted treatment and prevention strategies should be administered as early as possible and ideally before seroconversion. CLINICAL TRIALS REGISTRATION: NCT04405570.
Asunto(s)
COVID-19 , Enfermedades Transmisibles , Adulto , Anticuerpos Antivirales , Prueba de COVID-19 , Humanos , Inmunoglobulina A , Pacientes Ambulatorios , ARN Viral , SARS-CoV-2RESUMEN
HIV is an independent risk factor for lung disease, including chronic obstructive pulmonary disease (COPD) and emphysema. Angiotensin receptor blockers may be beneficial in COPD and emphysema through pathways that have been implicated in HIV-related lung disease. We performed a randomized comparison of the effects of losartan versus placebo on the plasma concentrations of the pneumoproteins, surfactant protein D (SPD) and club cell secretory protein (CCSP), in people living with HIV (PLWH). A total of 108 PLWH were included (52 assigned to losartan and 56 assigned to placebo). We found no difference in the change from baseline in log2 concentrations of CCSP or SPD over 1 year of follow-up. For SPD, we found a strong interaction by CD4+ counts, where those with CD4+ counts >350 cells/mm3 treated with losartan had more reduction (improvement) in SPD concentration than those treated with placebo (p value for interaction <.001). In conclusion, we did not find a beneficial effect of losartan on pneumoprotein concentrations in PLWH, but PLWH with higher CD4+ counts may have improvement in SPD when treated with losartan.
Asunto(s)
Infecciones por VIH , Enfermedad Pulmonar Obstructiva Crónica , Método Doble Ciego , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Losartán/uso terapéutico , Proyectos Piloto , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Pulmonar Obstructiva Crónica/metabolismoRESUMEN
Importance: Systemic corticosteroids are commonly used in treating severe COVID-19. However, the role of inhaled corticosteroids in the treatment of patients with mild to moderate disease is less clear. Objective: To determine the efficacy of the inhaled steroid ciclesonide in reducing the time to alleviation of all COVID-19-related symptoms among nonhospitalized participants with symptomatic COVID-19 infection. Design, Setting, and Participants: This phase 3, multicenter, double-blind, randomized clinical trial was conducted at 10 centers throughout the US and assessed the safety and efficacy of a ciclesonide metered-dose inhaler (MDI) for treating nonhospitalized participants with symptomatic COVID-19 infection who were screened from June 11, 2020, to November 3, 2020. Interventions: Participants were randomly assigned to receive ciclesonide MDI, 160 µg per actuation, for a total of 2 actuations twice a day (total daily dose, 640 µg) or placebo for 30 days. Main Outcomes and Measures: The primary end point was time to alleviation of all COVID-19-related symptoms (cough, dyspnea, chills, feeling feverish, repeated shaking with chills, muscle pain, headache, sore throat, and new loss of taste or smell) by day 30. Secondary end points included subsequent emergency department visits or hospital admissions for reasons attributable to COVID-19. Results: A total of 413 participants were screened and 400 (96.9%) were enrolled and randomized (197 [49.3%] in the ciclesonide arm and 203 [50.7%] in the placebo arm; mean [SD] age, 43.3 [16.9] years; 221 [55.3%] female; 2 [0.5%] Asian, 47 [11.8%] Black or African American, 3 [0.8%] Native Hawaiian or other Pacific Islander, 345 [86.3%] White, and 1 multiracial individuals [0.3%]; 172 Hispanic or Latino individuals [43.0%]). The median time to alleviation of all COVID-19-related symptoms was 19.0 days (95% CI, 14.0-21.0) in the ciclesonide arm and 19.0 days (95% CI, 16.0-23.0) in the placebo arm. There was no difference in resolution of all symptoms by day 30 (odds ratio, 1.28; 95% CI, 0.84-1.97). Participants who were treated with ciclesonide had fewer subsequent emergency department visits or hospital admissions for reasons related to COVID-19 (odds ratio, 0.18; 95% CI, 0.04-0.85). No participants died during the study. Conclusions and Relevance: The results of this randomized clinical trial demonstrated that ciclesonide did not achieve the primary efficacy end point of reduced time to alleviation of all COVID-19-related symptoms. Trial Registration: ClinicalTrials.gov Identifier: NCT04377711.
Asunto(s)
Tratamiento Farmacológico de COVID-19 , Pregnenodionas/normas , Administración por Inhalación , Adolescente , Adulto , Instituciones de Atención Ambulatoria/organización & administración , Instituciones de Atención Ambulatoria/estadística & datos numéricos , Instituciones de Atención Ambulatoria/tendencias , COVID-19/epidemiología , Método Doble Ciego , Femenino , Glucocorticoides/normas , Glucocorticoides/uso terapéutico , Humanos , Masculino , Inhaladores de Dosis Medida , Persona de Mediana Edad , Pacientes Ambulatorios/estadística & datos numéricos , Pregnenodionas/uso terapéuticoRESUMEN
BACKGROUND: While SARS-CoV-2 infectious virus isolation in outpatients with COVID-19 has been associated with viral RNA levels and symptom duration, little is known about the host, disease and viral determinants of infectious virus detection. METHODS: COVID-19 adult outpatients were enrolled within 7 days of symptom onset. Clinical symptoms were recorded via patient diary. Nasopharyngeal swabs were collected to quantitate SARS-CoV-2 RNA by reverse transcriptase polymerase chain reaction and for infectious virus isolation in Vero E6-cells. SARS-CoV-2 antibodies were measured in serum using a validated ELISA assay. RESULTS: Among 204 participants with mild-to-moderate symptomatic COVID19, the median nasopharyngeal viral RNA was 6.5 (IQR 4.7-7.6 log10 copies/mL), and 26% had detectable SARS-CoV-2 antibodies (IgA, IgM, IgG, and/or total Ig) at baseline. Infectious virus was recovered in 7% of participants with SARS-CoV-2 antibodies compared to 58% of participants without antibodies (probability ratio (PR)=0.12, 95% CI: 0.04, 0.36; p=0.00016). Infectious virus isolation was also associated with higher levels of viral RNA (mean RNA difference +2.6 log10, 95% CI: 2.2, 3.0; p<0.0001) and fewer days since symptom onset (PR=0.79, 95% CI: 0.71, 0.88 per day; p<0.0001). CONCLUSIONS: The presence of SARS-CoV-2 antibodies is strongly associated with clearance of infectious virus isolation. Seropositivity and viral RNA levels are likely more reliable markers of infectious virus clearance than subjective measure of COVID-19 symptom duration. Virus-targeted treatment and prevention strategies should be administered as early as possible and ideally before seroconversion. CLINICALTRIALSGOV IDENTIFIER: NCT04405570.
RESUMEN
BACKGROUND: Liver disease is an important cause of morbidity and mortality in people living with human immunodeficiency virus (PLWH), of which nonalcoholic fatty liver disease (NAFLD) is an increasingly recognized cause. There are limited data investigating NAFLD in HIV monoinfection and histologically defined disease. We aimed to identify who is at risk of fibrosis, NAFLD, and nonalcoholic steatohepatitis (NASH) among PLWH and explore the diagnostic accuracy of noninvasive markers of fibrosis. METHODS: This was a retrospective, cross-sectional, international, multicenter study including patients with HIV monoinfection, without chronic viral hepatitis or other known causes of chronic liver disease, who underwent liver biopsy for abnormal liver biochemistry and/or clinical suspicion of liver fibrosis. RESULTS: A total of 116 patients from 5 centers were included. Sixty-three (54%) had NAFLD, of whom 57 (92%) had NASH. Overall, 36 (31%) had advanced fibrosis (≥F3) and 3 (3%) had cirrhosis. Of the 53 cases without NAFLD, 15 (28%) had advanced fibrosis. Collagen proportionate area was similar between cases with and without NAFLD (3% vs 2%). Body mass index was independently associated with NAFLD (aOR, 1.2; 95% CI, 1.08-1.34), and type 2 diabetes was independently associated with advanced fibrosis (aOR, 3.42; 95% CI, 1.00-11.71). The area under the curve for advanced fibrosis was 0.65 and 0.66 for both NAFLD Fibrosis Score (NFS) and FIB-4. Cutoff values of -1.455 (NFS) and 1.3 (FIB-4) have negative-predictive values of 0.80 and 0.82, respectively. CONCLUSIONS: Advanced fibrosis is strongly associated with type 2 diabetes in PLWH. Serological markers require further optimization.
Asunto(s)
Diabetes Mellitus Tipo 2 , Infecciones por VIH , Enfermedad del Hígado Graso no Alcohólico , Biopsia , Índice de Masa Corporal , Estudios Transversales , Diabetes Mellitus Tipo 2/complicaciones , Fibrosis , VIH , Infecciones por VIH/complicaciones , Infecciones por VIH/patología , Humanos , Hígado/patología , Cirrosis Hepática/patología , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Estudios RetrospectivosRESUMEN
BACKGROUND: Persistent inflammation and incomplete immune recovery among persons with HIV (PHIV) are associated with increased disease risk. We hypothesized that the angiotensin receptor blocker (ARB) losartan would reduce inflammation by mitigating nuclear factor (NF)κB responses and promote T-cell recovery via inhibition of transforming growth factor-beta (TGFß)-mediated fibrosis. METHODS: Losartan (100âmg) versus placebo over 12 months was investigated in a randomized (1â:â1) placebo-controlled trial, among PHIV age at least 50 years, receiving antiretroviral therapy (ART), with HIV RNA less than 200âcopies/ml and CD4+ cell count 600âcells/µl or less. Inflammation, fibrosis and myocardial biomarkers were measured in blood using ELISA, electrochemiluminescence and immunoturbidimetric methods, and T-cell and monocyte phenotypes were assessed with flow cytometry among a subset of participants. Changes over follow-up in (log-2 transformed) biomarkers and cell phenotypes (untransformed) were compared between losartan and placebo arms using linear mixed models. RESULTS: Among 108 PHIV (nâ=â52 to losartan; nâ=â56 to placebo), 97% had a month 12 visit. Median age was 57 years and baseline CD4+ cell count was 408âcells/µl. Losartan treatment was not associated with an improvement in interleukin-6 levels, or other blood measures of inflammation, immune activation, fibrosis activity or myocardial function. CD4+ and CD8+ T cells also did not differ by treatment group. Losartan reduced SBP and DBP by 6 and 5âmmHg, respectively. CONCLUSION: Among older PHIV with viral suppression, losartan did not improve blood measures of inflammation nor T-cell immune recovery. Losartan treatment is unlikely to reduce inflammation associated comorbidities to a clinically meaningful degree, beyond the benefits from lowering blood pressure. CLINICALTRIALSGOV: NCT02049307.
Asunto(s)
Infecciones por VIH , Losartán , Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina , Fibrosis , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Inflamación , Persona de Mediana EdadRESUMEN
In recent years, there has been an increasing number of clinical trials for the treatment of nonalcoholic steatohepatitis (NASH). People living with human immunodeficiency virus (PLWH) are commonly excluded from these studies, usually due to concerns over drug-drug interactions associated with antiretroviral therapy. The Steatohepatitis in HIV Emerging Research Network, a group of international experts in hepatology and infectious diseases, discusses our current understanding on the interaction between human immunodeficiency virus and NASH, and the issues related to the inclusion of PLWH in NASH clinical trials. Recent trials addressing NASH treatment in PLWH are discussed. The risk of drug-drug interactions between antiretroviral therapy and aramchol, cenicriviroc, elafibranor, obeticholic acid and resmetirom (MGL-3196), which are currently in phase 3 trials for the treatment of NASH, are reviewed. A model for trial design to include PLWH is proposed, strongly advocating for the scientific community to include this group as a subpopulation within studies.
Asunto(s)
Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Antirretrovirales/uso terapéutico , Chalconas/uso terapéutico , Ácido Quenodesoxicólico/análogos & derivados , Ácido Quenodesoxicólico/uso terapéutico , Ácidos Cólicos/uso terapéutico , Ensayos Clínicos Fase III como Asunto , Interacciones Farmacológicas , Infecciones por VIH/epidemiología , Humanos , Imidazoles/uso terapéutico , Enfermedad del Hígado Graso no Alcohólico/epidemiología , Propionatos/uso terapéutico , Piridazinas/uso terapéutico , Sulfóxidos/uso terapéutico , Uracilo/análogos & derivados , Uracilo/uso terapéuticoRESUMEN
BACKGROUNDHIV-infected patients with poor virologic control and multidrug-resistant virus have limited therapeutic options. The current study was undertaken to evaluate the safety, immunologic effects, and antiviral activity of peripheral lymphocytes transferred from an elite controller, whose immune system is able to control viral replication without antiretroviral medications, to an HLA-B*2705-matched progressor.METHODSApproximately 22 billion cells were collected from an elite controller by lymphapheresis and infused within 6 hours into a recipient with a preinfusion CD4+ T cell count of 10 cells/µL (1%) and HIV plasma viral load of 114,993 copies/mL.RESULTSDonor cells were cleared from the recipient's peripheral blood by day 8. A transient decrease in viral load to 58,421 (day 3) was followed by a rebound to 702,972 (day 6) before returning to baseline values by day 8. The decreased viral load was temporally associated with peak levels of donor T cells, including CD8+ T cells that had high levels of expression of Ki67, perforin, and granzyme B. Notably, recipient CD8+ T cells also showed increased expression of these markers, especially in HIV-specific tetramer-positive cells.CONCLUSIONThese results suggest that the adoptive transfer of lymphocytes from an HIV-infected elite controller to an HIV-infected patient with progressive disease may be able to perturb the immune system of the recipient in both positive and negative ways.TRIAL REGISTRATIONClinicalTrials.gov NCT00559416.FUNDINGIntramural Research Programs of the US NIH Clinical Center and the National Institute of Allergy and Infectious Diseases (NIAID); the National Cancer Institute.
Asunto(s)
Traslado Adoptivo/métodos , Linfocitos T CD4-Positivos/trasplante , Infecciones por VIH/terapia , VIH-1/inmunología , Replicación Viral/inmunología , Adulto , Recuento de Linfocito CD4 , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Granzimas/metabolismo , Infecciones por VIH/sangre , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Antígeno HLA-B27/inmunología , Prueba de Histocompatibilidad , Humanos , Antígeno Ki-67/metabolismo , Masculino , Persona de Mediana Edad , Perforina/metabolismo , Trasplante Heterólogo/métodos , Resultado del Tratamiento , Carga ViralRESUMEN
Objective: To characterize cerebral arterial remodeling in HIV-infected (HIV+) individuals in-vivo, and to study its clinical and immunological associations. Methods: T2*-weighted magnetic resonance imagining sequences was used to determine cross-sectional area (vascular caliber) of the anterior (A1 segment) and middle (M1 segment) cerebral arteries in HIV- (control) and HIV+ subjects on antiretroviral therapy. Correlations of A1 caliber with clinical, demographic parameters, and immunological markers in cerebrospinal fluid (CSF) were determined using multivariable analyses. Results: A1 and M1 calibers from 22 HIV- control subjects (age: median 48.5 years, range 22-60 years, 55% male) and 61 HIV+ subjects (age: median 53 years, range 25-60 years, 67% male) were studied. ANCOVA, adjusting for ethnicity and sex (age was not correlated with M1 or A1 caliber in either group), revealed that HIV+ subjects had larger caliber in the A1 segment than HIV- subjects (4.95 ± 0.14 mm2, and 4.47 ± 0.21 mm2 respectively, p = 0.048), but caliber of the M1 segment did not differ among the groups (7.21 ± 0.14 mm2 and 7.09 ± 0.23 mm2 respectively, p = 0.65). In the HIV+ cohort, longer disease duration and higher current CD4 T-cell count were associated with reduced A1 caliber (r =-0.42 and -0.33 respectively, p < 0.05). In addition, increase in cardiovascular disease risk (CVD risk) was associated with a decrease in A1 caliber in the HIV group (r = -0.35, p < 0.05). Conclusions: This cross-sectional study reveals an increase in A1 caliber in the HIV+ cohort, compared to control subjects, which is especially prominent in early phase of the disease. This increase in caliber may be associated with acute pathological processes in HIV during the initial stages of infection resulting in loss of compliance or thinning of the arterial wall. At later stages, such changes may be confounded by arteriosclerotic changes that are common in later stages of HIV infection. This study suggests there is extensive vessel remodeling in various stages of infection. Long-term longitudinal follow-up of this cohort is planned to further verify this hypothesis and to better understand this MRI marker of intracranial vascular caliber.
RESUMEN
Persons living with HIV (PLWH) have disproportionately high rates of both cigarette smoking and tobacco-induced negative health outcomes. The goal of this qualitative systematic review was to identify gaps in the existing literature and future directions for smoking cessation support for PLWH. Three online databases were searched from their inception through December 31, 2017, using designated search terms. Peer-reviewed English-language articles that documented an intervention designed to increase smoking cessation among PLWH were reviewed. Data were abstracted using a standardized form to document study and intervention characteristics and results. Thirty-two articles, describing 28 unique intervention studies, met inclusion criteria. Interventions consisted primarily of combinations of counseling, pharmacotherapy, and the use of information and communications technology; few interventions were implemented at the clinic level. Thirteen interventions resulted in significant improvements in cessation-related outcomes. Information and communications technology and clinic-level interventions had the greatest potential for increasing smoking cessation among PLWH. Efficacious interventions designed for PLWH in the US South, and for groups of PLWH facing additional health disparities (e.g., communities of color and sexual and gender minorities), are needed. There is also a need for more rigorous research designs to test the efficacy of interventions designed to increase cessation-related outcomes among PLWH.
Asunto(s)
Infecciones por VIH/psicología , Infecciones por VIH/terapia , Cese del Hábito de Fumar/psicología , Fumar/psicología , Fumar/terapia , Consejo , VIH/aislamiento & purificación , Infecciones por VIH/epidemiología , Humanos , Investigación Cualitativa , Fumar/epidemiología , Cese del Hábito de Fumar/métodosRESUMEN
BACKGROUND: The goal of antiretroviral therapy (ART) is to suppress HIV-1 replication and reconstitute CD4+ T cells. Here, we report on HIV-infected individuals who had a paradoxical decline in CD4+ T cells despite ART-mediated suppression of plasma HIV-1 load (pVL). We defined such an immunological outcome as extreme immune decline (EXID). METHODS: EXID's clinical and immunological characteristics were compared to immunological responders (IRs), immunological nonresponders (INRs), healthy controls (HCs), and idiopathic CD4+ lymphopenia (ICL) patients. T cell immunophenotyping and assembly/activation of inflammasomes were evaluated by flow cytometry. PBMC transcriptome analysis and genetic screening for pathogenic variants were performed. Levels of cytokines/chemokines were measured by electrochemiluminescence. Luciferase immunoprecipitation system and NK-mediated antibody-dependent cellular cytotoxicity (ADCC) assays were used to identify anti-lymphocyte autoantibodies. RESULTS: EXIDs were infected with non-B HIV-1 subtypes and after 192 weeks of consistent ART-mediated pVL suppression had a median CD4+ decrease of 157 cells/µl, compared with CD4+ increases of 193 cells/µl and 427 cells/µl in INR and IR, respectively. EXID had reduced naive CD4+ T cells, but similar proportions of cycling CD4+ T cells and HLA-DR+CD38+CD8+ T cells compared with IR and INR. Levels of inflammatory cytokines were also similar in EXID and INR, but the IL-7 axis was profoundly perturbed compared with HC, IR, INR, and ICL. Genes involved in T cell and monocyte/macrophage function, autophagy, and cell migration were differentially expressed in EXID. Two of the 5 EXIDs had autoantibodies causing ADCC, while 2 different EXIDs had an increased inflammasome/caspase-1 activation despite consistently ART-suppressed pVL. CONCLUSIONS: EXID is a distinct immunological outcome compared with previously described INR. Anti-CD4+ T cell autoantibodies and aberrant inflammasome/caspase-1 activation despite suppressed HIV-1 viremia are among the mechanisms responsible for EXID.