Faculty Bibliography
Searched for:
person:hsur02
in-biosketch:true
Total Results:
40
ACE-i/ARB use and outcomes after hospitalized AKI [Meeting Abstract]
Background: The risk-benefit ratio of ACE-I/ARB therapy after an AKI episode is unclear.
Method(s): We studied 1570 patients recently discharged from hospital and enrolled in a multi-center prospective cohort study (ASSESS-AKI). Follow-up began 3 months after index hospitalization and continued through November 2018. Half of the participants had AKI during the index hospitalization. ACE-I/ARB use and covariates were ascertained 3 months after discharge from the index hospitalization. We used multivariable Cox regression adjusting for demographics, cardiovascular disease, diabetes mellitus, heart failure (HF), blood pressure, urine protein to creatinine ratio, and eGFR to examine the association between ACE-I/ARB use and subsequent death, AKI (>=50% difference between peak and nadir inpatient serum creatinine), renal progression (ESRD or halving of eGFR), and adjudicated HF events.
Result(s): Among study participants who did not have AKI during index hospitalization (N=806), mean age was 65 years, mean eGFR 74 ml/min/1.73m2, and 45% self-reported use of ACE-I/ARB 3 months after hospitalization. Among study participants who did have AKI during index hospitalization (N=764), mean age was 64 years, mean eGFR 65 ml/min/1.73m2, and 50% self-reported use of ACE-I/ARB 3 months after hospitalization. Mean follow-up time was 3.6 years. ACE-I/ARB therapy 3 months after an AKI hospitalization was associated with a lower risk of another hospitalized AKI event and a lower risk of death (Table).
Conclusion(s): Use of ACE-I/ARB in survivors of hospitalized AKI was not associated with increased risk of subsequent AKI but was associated with lower risk of death
Method(s): We studied 1570 patients recently discharged from hospital and enrolled in a multi-center prospective cohort study (ASSESS-AKI). Follow-up began 3 months after index hospitalization and continued through November 2018. Half of the participants had AKI during the index hospitalization. ACE-I/ARB use and covariates were ascertained 3 months after discharge from the index hospitalization. We used multivariable Cox regression adjusting for demographics, cardiovascular disease, diabetes mellitus, heart failure (HF), blood pressure, urine protein to creatinine ratio, and eGFR to examine the association between ACE-I/ARB use and subsequent death, AKI (>=50% difference between peak and nadir inpatient serum creatinine), renal progression (ESRD or halving of eGFR), and adjudicated HF events.
Result(s): Among study participants who did not have AKI during index hospitalization (N=806), mean age was 65 years, mean eGFR 74 ml/min/1.73m2, and 45% self-reported use of ACE-I/ARB 3 months after hospitalization. Among study participants who did have AKI during index hospitalization (N=764), mean age was 64 years, mean eGFR 65 ml/min/1.73m2, and 50% self-reported use of ACE-I/ARB 3 months after hospitalization. Mean follow-up time was 3.6 years. ACE-I/ARB therapy 3 months after an AKI hospitalization was associated with a lower risk of another hospitalized AKI event and a lower risk of death (Table).
Conclusion(s): Use of ACE-I/ARB in survivors of hospitalized AKI was not associated with increased risk of subsequent AKI but was associated with lower risk of death
EMBASE:633771826
ISSN: 1533-3450
CID: 4754862
Psychiatric outcomes observed in patients living with HIV using six common core antiretrovirals in the Observational Pharmaco-Epidemiology Research and Analysis database
Background/UNASSIGNED:Psychiatric outcomes are common among people living with HIV and may be associated with specific antiretroviral use. We evaluated the occurrence of psychiatric outcomes in patients taking dolutegravir (DTG)-containing regimens compared with five other core agents. Methods/UNASSIGNED:Patients in the OPERA database prescribed regimens based on DTG, efavirenz (EFV), raltegravir (RAL), darunavir (DRV), rilpivirine (RPV), or elvitegravir (EVG) for the first time between 1 January 2013 and 31 December 2015 were analyzed. Psychiatric outcomes included diagnoses of anxiety, depression, insomnia, or suicidality during core agent exposure. Multivariable Cox analysis models were used to assess time to psychiatric outcomes between core agents stratified by psychiatric history, with DTG as the referent. Results/UNASSIGNED:EVG and DRV). Conclusions/UNASSIGNED:In a large cohort of HIV+ patients in care, patients with a psychiatric history appeared channeled towards drugs with known favorable psychiatric safety profiles, including DTG. Despite this, DTG exposure was not associated with an increased risk of psychiatric outcomes during follow up in patients with or without a psychiatric history.
PMCID:6287328
PMID: 30546862
ISSN: 2042-0986
CID: 3556372
Journal of acquired immune deficiency syndromes. JAIDS. 2017:74(4):423-431.DOI: 10.1097/QAI.0000000000001269
Psychiatric Symptoms in Patients Receiving Dolutegravir
INTRODUCTION: Psychiatric symptoms are reported to occur frequently in people living with HIV and may be associated with specific antiretrovirals. We analysed psychiatric symptoms observed with dolutegravir and other frequently prescribed anchor drugs. METHODS: Selected psychiatric symptoms (insomnia, anxiety, depression, and suicidality) occurring in HIV-positive patients during dolutegravir treatment across 5 randomized clinical trials (3 double-blind), in the Observational Pharmaco-Epidemiology Research & Analysis (OPERA(R)) cohort, and among cases spontaneously reported to ViiV Healthcare were analysed. RESULTS: In clinical trials, psychiatric symptoms were reported at low and similar rates in patients receiving dolutegravir or comparators (atazanavir, darunavir, efavirenz, or raltegravir). Insomnia was most commonly reported. The highest rates were observed in SINGLE (dolutegravir 17%, efavirenz 12%), with consistently lower rates in the other trials (dolutegravir: 3%-8% versus comparator: 3%-7%). More efavirenz-treated patients withdrew because of psychiatric symptoms than patients treated with other anchor drugs. In OPERA, history of psychiatric symptoms at baseline was lowest in efavirenz-treated patients compared with patients treated with dolutegravir, raltegravir, or darunavir. Despite baseline differences, prevalence and incidence during treatment were similar across the 4 anchor drugs. Withdrawal rates for psychiatric symptoms were lowest for dolutegravir (0%-0.6%) and highest for raltegravir (0%-2.5%). Spontaneously reported events were similar in nature to clinical trial data. CONCLUSIONS: Analysis of 3 different data sources shows that, similar to other frequently prescribed anchor drugs to treat HIV infection, psychiatric symptoms are also reported in DTG-treated patients. These events are reported with low frequency and rarely necessitate DTG discontinuation.
PMCID:5321108
PMID: 27984559
ISSN: 1944-7884
CID: 2363762
Virologic Effectiveness of Abacavir/Lamivudine with Darunavir/Ritonavir Versus Other Protease Inhibitors in Treatment-Experienced HIV-Infected Patients in Clinical Practice
BACKGROUND AND OBJECTIVES/OBJECTIVE:The standard of care for HIV treatment is a three-drug regimen consisting of two nucleoside reverse transcriptase inhibitors (NRTIs) and either a non-nucleoside reverse transcriptase inhibitor, a protease inhibitor (PI) or an integrase strand transfer inhibitor. Darunavir boosted with ritonavir (DRV/r) is the only preferred PI in the US Department of Health and Human Services (DHHS) HIV treatment guidelines for antiretroviral-naïve patients, recommended in combination with tenofovir/emtricitabine for antiretroviral-naïve patients. For treatment-experienced and certain antiretroviral-naïve patients, abacavir and lamivudine (ABC/3TC) in combination with DRV/r is considered an effective and tolerable alternative, despite limited research on the effectiveness of this particular combination. This study evaluated virologic outcomes in treatment-experienced patients taking ABC/3TC + DRV/r compared to treatment-experienced patients taking ABC/3TC with any other PI. METHODS:) cohort, a prospective observational cohort reflecting routine medical care. Viral load measurements taken during follow-up were compared between patients taking ABC/3TC + DRV/r and ABC/3TC with a PI other than DRV/r. Logistic regression models were fit to assess the association between regimen exposure and viral load suppression. RESULTS:; p = 0.59] while being treated with the regimen of interest. CONCLUSIONS:Patients receiving ABC/3TC + DRV/r appear to experience similar treatment benefit to patients taking ABC/3TC with other PIs in terms of achieving suppression, as well as absolute reductions in viral load and CD4 lymphocyte gains.
PMCID:5209413
PMID: 27587070
ISSN: 1179-1918
CID: 4916772
Applications for detection of acute kidney injury using electronic medical records and clinical information systems: Workgroup statements from the 15th ADQI Consensus Conference
Electronic medical records and clinical information systems are increasingly used in hospitals and can be leveraged to improve recognition and care for acute kidney injury. This Acute Dialysis Quality Initiative (ADQI) workgroup was convened to develop consensus around principles for the design of automated AKI detection systems to produce real-time AKI alerts using electronic systems. AKI alerts were recognized by the workgroup as an opportunity to prompt earlier clinical evaluation, further testing and ultimately intervention, rather than as a diagnostic label. Workgroup members agreed with designing AKI alert systems to align with the existing KDIGO classification system, but recommended future work to further refine the appropriateness of AKI alerts and to link these alerts to actionable recommendations for AKI care. The consensus statements developed in this review can be used as a roadmap for development of future electronic applications for automated detection and reporting of AKI.
EMBASE:613401218
ISSN: 2054-3581
CID: 2377692
"Predictors of CIMT Atherosclerosis Differs Between HIV Infected and Uninfected Individuals" [Meeting Abstract]
ISI:000374763800516
ISSN: 1532-5415
CID: 2118772
Cytoxan enhancement of SB-728-T engraftment: A strategy to improve anti-HIV Response [Meeting Abstract]
Background: Administration of CCR5 modified autologous CD4 cells (SB-728-T) is safe and well-tolerated and results in increases in total CD4 counts. The modified cells traffic to lymphoid tissues and have a selective survival advantage during ART treatment interruption (TI). Studies in CCR5 DELTA32 heterozygote HIV subjects showed VL reductions during TI correlated with levels of engraftment of circulating bi-allelic CCR5-modified cells supporting the importance of maximizing engraftment of modified cells. We have previously presented preliminary data on the use of low dose cyclophosphamide (CTX) to enhance this process. We now report the final results of this dose ranging study. Methods: A dose escalation study of IV CTX, with doses ranging from 100 mg/m2 to 2 g/m2 (n=3-6/cohort), administered 1-3 days prior to SB-728-T (>90% CD4, <1% CD8) infusion was performed in 18 aviremic, ART-treated HIV subjects with CD4 T cells > 500/uL. Results: CTX was well tolerated with low grade GI side-effects at doses up to 1 g/m2. Grade 3 and 4 neutropenia requiring G-CSF developed at 1.5 and 2.0 g/m2 CTX. A dose-related increase in CD4 count and engraftment of bi-allelic CCR5 modified cells was observed with CTX doses up to 1 g/m2 but did not increase at 2.0 and 1.5 g/m2. By comparison, there was a progressive decline in CD8 cells with CTX dose escalation. Data in the table is expressed as Mean + SE; changes as Day 7 relative to pre-treatment baseline. A 1-log VL reduction from peak was seen in 1 subject each at 100 and 500 mg/m2 of CTX while 1 subject each at the 1 and 1.5 g/m2 dose level had a 2-log decline during TI. At the conclusion of the study, 3 additional subjects were conditioned with 1 g/m2 of CTX and administered CCR5 modified T cells containing 40.5+5.6% CD4 and 46.9+6.4% CD8 T cells. CD8 count increased by a mean of 2590/uL at 7 days in the 2 subjects with data available for analysis. The VL in the first subject remains undetectable 5 weeks after TI initiation versus a median duration of 15+3 days in subjects who received only SB-728T. (Table presented) Conclusions: CTX conditioning is well tolerated and was associated with increased engraftment of CCR5-modified T cells at doses up to 1 g/m2 in HIV subjects. CTX conditioning may be a useful strategy to maximize the engraftment and anti-viral effects of SB-728-T. The effects of co-administering CD8 cells with SB-728-T on VL will be presented
EMBASE:72119330
ISSN: 2161-5861
CID: 1907462
Rapid Progression to Decompensated Cirrhosis, Liver Transplant, and Death in HIV-Infected Men After Primary Hepatitis C Virus Infection
Background. We and others have shown that primary hepatitis C (HCV) infection in men infected with human immunodeficiency virus (HIV) causes early-onset liver fibrosis; however, little is known about the long-term natural history of the liver disease in these HIV-infected men. Methods. We followed a cohort of HIV-infected men with primary HCV infection in New York City. Results. Four men who were not cured after their primary HCV infection developed decompensated cirrhosis within 17 months to 6 years after primary HCV infection. Three died within 8 years of primary HCV infection, and 1 survived after liver transplant done 2 years after primary HCV infection. Three of the 4 men had AIDS at the time of primary HCV infection, and the most rapid progression occurred in the 2 men with the lowest CD4 counts at the time of HCV infection. Liver histopathology was most consistent with HCV-induced damage even though some had exposures to other potential hepatotoxins. Conclusions. Primary HCV infection resulted in decompensated cirrhosis and death within 2-8 years in 4 HIV-infected men. The rapid onset of fibrosis due to primary HCV infection in HIV-infected men cannot therefore be considered benign. The rate of continued progression to liver failure may be proportional to the degree of underlying immunocompromise caused by HIV infection. More research is needed to better define the mechanisms behind accelerated liver damage.
PMCID:3588118
PMID: 23264364
ISSN: 1058-4838
CID: 264282
The major genetic determinants of HIV-1 control affect HLA class I peptide presentation
Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection
PMCID:3235490
PMID: 21051598
ISSN: 1095-9203
CID: 134400
Modulation of K65R selection by zidovudine inclusion: analysis of HIV resistance selection in subjects with virologic failure receiving once-daily abacavir/lamivudine/zidovudine and tenofovir DF (study COL40263)
COL40263 was a pilot 48-week, open-label, multicenter study evaluating the efficacy and safety of once-daily coformulated abacavir/lamivudine/zidovudine plus tenofovir in ART-naive, HIV-infected subjects. We examined the patterns of resistance that were selected on-therapy through 48 weeks in subjects with virologic nonresponse (VF). A total of 123 antiretroviral-naive HIV-1-infected subjects with plasma HIV-1 RNA > or = 30,000copies/ml were enrolled. For subjects with confirmed VF (HIV-1 RNA > or = 400 copies/ml at week 24 or later), HIV population genotypic and phenotypic analysis was performed. Of the 123 enrolled subjects, 14 (11%) had confirmed plasma HIV-1 RNA > or = 400 copies/ml through week 48. Of these subjects, 3/14 had evidence of drug resistance at baseline: 2/14 had HIV with K103N, Y188F/H/L/Y, and/or T215A and 1/14 had reduced zidovudine susceptibility. At the last time point analyzed, 4/14 subjects had wild-type HIV, while 10/14 subjects had HIV with either thymidine analogue mutations (TAMS) alone (3/10), TAMS + M184V (4/10), M184V only (1/10), or K65R/K (2/10). Matched phenotype was obtained for 13/14 subjects and 8/13 (62%) subjects had reduced susceptibility to one or more study drugs: 2/13 tenofovir, 3/13 abacavir, 4/13 zidovudine, and 7/13 lamivudine. The resistance pattern in COL40263 subjects with VF differs significantly from that reported for tenofovir-containing triple-nucleoside regimens. TAMs were detected in the majority (7/10) of samples from subjects with VF who selected any resistance mutation. These data suggest that TAMs selection is a preferred resistance route of this combination, with zidovudine modulating the resistance pathway against selection for K65R
PMID: 19563238
ISSN: 1931-8405
CID: 141936
