Nwora Lance Okeke

Statin Utilization and Recommendations Among HIV and HCV-Infected Veterans: A Cohort Study

BACKGROUND Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections are associated with increased risk of cardiovascular disease (CVD). The potential impact of recently updated cholesterol guidelines on treatment of HIV- and HCV-infected veterans is unknown. METHODS We performed a retrospective cohort study to assess statin use and recommendations among 13 579 HIV-infected, 169 767 HCV-infected, and 6628 HIV/HCV-coinfected male veterans aged 40-75 years. Prior 2004 Adult Treatment Panel (ATP-III) guidelines were compared with current 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol guidelines and 2014 US Department of Veterans Affairs (VA)/US Department of Defense (DoD) joint clinical practice guidelines using laboratory, medication, and comorbidity data from the VA Clinical Case Registry from 2008 through 2010. RESULTS Using risk criteria delineated by the ATP-III guidelines, 50.6% of HIV-infected, 45.9% of HCV-infected, and 33.8% of HIV/HCV-coinfected veterans had an indication for statin therapy. However, among those eligible, 22.7%, 30.5%, and 31.5%, respectively, were not receiving ATP-III recommended statin therapy. When current cholesterol guidelines were applied by VA/DoD and ACC/AHA criteria, increases in recommendations for statins were found in all groups (57.3% and 66.1% of HIV-infected, 64.4% and 73.7% of HCV-infected, 49.1% and 58.5% of HIV/HCV-coinfected veterans recommended). CONCLUSIONS Statins were underutilized among veterans infected with HIV, HCV, and HIV/HCV according to previous ATP-III guidelines. Current VA/DoD and ACC/AHA guidelines substantially expand statin recommendations and widen the gap of statin underutilization in all groups. These gaps in care present an opportunity to improve CVD prevention efforts in these at-risk populations.

Hypertension Among HIV-infected Patients in Clinical Care, 1996–2013

BACKGROUND Persons infected with human immunodeficiency virus (HIV) are at higher risk for major cardiovascular disease (CVD) events than uninfected persons. Understanding the epidemiology of major traditional CVD risk determinants, particularly hypertension, in this population is needed. METHODS The study population included HIV-infected patients participating in the UNC CFAR HIV Clinical Cohort from 1996 to 2013. Annual incidence rates of hypertension were calculated. Multivariable Poisson models were fit to identify factors associated with incident hypertension. RESULTS 3141 patients contributed 21 956 person-years (PY) of follow-up. Overall, 57% patients were black, 28% were women, and the median age was 35 years. Hypertension age-standardized incidence rates increased from 1.68 cases per 100 PYs in 1996 to 5.35 cases per 100 PYs in 2013 (P < .001). In adjusted analyses, hypertension rates were higher among obese patients (incidence rate ratio [IRR] 1.70, 95% confidence interval [CI], 1.43-2.02), and those with diabetes mellitus (IRR 1.44, 95% CI, 1.14-1.83) and renal insufficiency (IRR 1.36, 95% CI, 1.16-1.61), but lower among patients with a CD4 nadir of ≥500 cells/mm(3) (IRR 0.73, 95% CI, .53-1.01). CONCLUSIONS The incidence of hypertension increased from 1996 to 2013, alongside increases in traditional hypertension risk determinants. Notably, HIV-related immunosuppression and ongoing viral replication may contribute to an increased hypertension risk. Aggressive CVD risk factor management, early HIV diagnosis, linkage to care, antiretroviral therapy initiation, and durable viral suppression, will be important components of a comprehensive primary CVD prevention strategy in HIV-infected persons.

History of AIDS in HIV-Infected Patients Is Associated With Higher In-Hospital Mortality Following Admission for Acute Myocardial Infarction and Stroke

BACKGROUND Although human immunodeficiency virus (HIV)-infected persons are at increased risk for major cardiovascular events, short-term prognosis after these events is unclear. METHODS To determine the association between HIV infection and acute myocardial infarction (AMI) and stroke outcomes, we analyzed hospital discharge data from the Nationwide Inpatient Sample (NIS) between 2002 and 2012. Multivariable logistic regression was used to evaluate the association between HIV infection and in-hospital death after AMI or stroke. RESULTS Overall, 18 369 785 AMI/stroke hospitalizations were included in the analysis. Patients with a history of AIDS were significantly more likely than uninfected patients to die during hospitalization after admission for AMI or stroke (odds ratio, 3.03 [95% confidence interval {CI}, 1.71-5.38] for AMI and 2.59 [95% CI, 1.97-3.41] for stroke). Additionally, patients with AIDS were more likely than HIV-uninfected patients to be discharged to nonhospital inpatient facilities after admission for AMI (OR, 3.14 [95% CI, 1.72-5.74]) or stroke (OR, 1.45; 95% CI, 1.12-1.87). There was a minimal difference in either outcome between HIV-infected patients without a history of AIDS and uninfected patients. CONCLUSIONS Patients with a history of AIDS were significantly more likely than uninfected patients to die during hospitalization after admission for AMI or stroke. This disparity was not observed when infected patients without a history of AIDS were compared to uninfected patients, implying that preserving immune function may improve cardiovascular outcomes in HIV-infected persons.

Coronary artery disease risk reduction in HIV-infected persons: a comparative analysis

ABSTRACT Despite an increased risk of coronary artery disease (CAD) in persons infected with human immunodeficiency virus (HIV), few data are available on primary prevention of CAD in this population. In this retrospective cohort study, HIV-infected patients treated in an academic medical center HIV Specialty Clinic between 1996 and 2010 were matched by age, gender, and ethnicity to a cohort of presumed uninfected persons followed in an academic medical center Internal Medicine primary care clinic. We compared CAD primary prevention care practices between the two clinics, including use of aspirin, HMG-CoA reductase inhibitors (“statins”), and anti-hypertensive drugs. CAD risk between the two groups was assessed with 10-year Framingham CAD risk scores. In the comparative analysis, 890 HIV-infected persons were compared to 807 controls. Ten-year Framingham CAD Risk Scores were similar in the two groups (median, 3; interquartile range [IQR], 0–5). After adjusting for relevant risk factors, HIV-infected persons were less likely to be prescribed aspirin (odds ratio [OR] 0.53; 95% confidence interval [CI], 0.40–0.71), statins (OR, 0.70; 95% CI, 0.53–0.92), and anti-hypertensive drugs (OR, 0.63; 95% CI, 0.50–0.79) than persons in the control group. In summary, when compared to demographically similar uninfected persons, HIV-infected persons treated in an HIV specialty clinic were less likely to be prescribed medications appropriate for CAD risk reduction. Improving primary preventative CAD care in HIV specialty clinic populations is an important step toward diminishing risk of heart disease in HIV-infected persons.

Metabolites predict cardiovascular disease events in persons living with HIV: a pilot case–control study

IntroductionPersons living with HIV (PLWH) are at higher risk for cardiovascular disease (CVD) events than uninfected persons. Current risk-stratification methods to define PLWH at highest risk for CVD events are lacking.MethodsUsing tandem flow injection mass spectrometry, we quantified plasma levels of 60 metabolites in 24 matched pairs of PLWH [1:1 with and without known coronary artery disease (CAD)]. Metabolite levels were reduced to interpretable factors using principal components analysis.ResultsFactors derived from short-chain dicarboxylacylcarnitines (SCDA) (p = 0.08) and glutamine/valine (p = 0.003) were elevated in CAD cases compared to controls.ConclusionSCDAs and glutamine/valine may be valuable markers of cardiovascular risk among persons living with HIV in the future, pending validation in larger cohorts.

Fever and Rash in a Patient With Hepatitis

Clinical Review & Education JAMA Clinical Challenge Fever and Rash in a Patient With Hepatitis Meredith E. Clement, MD; N. Lance Okeke, MD; Charles B. Hicks, MD Figure. Left, Pigmented, macular rash on palmar surface of left hand. Right, Pigmented, macular rash on plantar surface of left foot. A 56-year-old man with longstanding human immunodeficiency vi- rus (HIV) infection presented for evaluation of new-onset fatigue and malaise. He was adherent to his antiretroviral therapy (ART) regimen (tenofovir/emtricitabine, raltegravir), with a recent CD4 lymphocyte count of 382 cells/mm 3 (18%) and HIV RNA below the level of assay detection. Initial evaluation was unremarkable except for new abnor- malities in hepatic laboratory results (alanine aminotransferase, 217 U/L (3.6 μkat/L); aspartate aminotransferase, 149 U/L (2.5 μkat/L); alka- line phosphatase, 610 U/L (10.2 μkat/L); total bilirubin, 2.2 mg/dL (37.6 μmol/L); and albumin, 3.1 g/dL). He denied having jaundice, pruritus, abdominal pain, or other gastrointestinal symptoms and re- ported no alcohol intake or recent use of new medications. He reported taking ator- Quiz at jama.com vastatin for dyslipidemia and testosterone gel for hypogonadism. Test results for hepatitis A, B, and C were nega- tive, as were results for anti–smooth muscle and antimitochondrial an- tibodies. Results of a serum antinuclear antibody test were positive, with a titer of 1:640. Liver biopsy demonstrated moderately active inter- face and lobular hepatitis with plasma cells and periportal cholestasis, findings suggestive of autoimmune hepatitis. The patient was started on prednisone and azathioprine. Shortly thereafter he developed fe- ver to 38.9°C and a macular rash that involved his palms and soles (Figure). Physical examination was otherwise normal. WHAT WOULD YOU DO NEXT? A. Stop atorvastatin secondary to statin-associated hepatitis B. Continue prednisone and azathio- prine for autoimmune hepatitis C. Check a rapid plasma reagin (RPR) test D. Biopsy the skin lesions JAMA July 28, 2015 Volume 314, Number 4 (Reprinted) Copyright 2015 American Medical Association. All rights reserved. Downloaded From: http://jama.jamanetwork.com/ by a University of California - San Diego User on 07/28/2015 jama.com

Prevalence and Transmission Dynamics of HIV-1 Transmitted Drug Resistance in a Southeastern Cohort

Abstract Background Transmitted drug resistance (TDR) compromises clinical management and outcomes. Transmitted drug resistance surveillance and identification of growing transmission clusters are needed in the Southeast, the epicenter of the US HIV epidemic. Our study investigated prevalence and transmission dynamics in North Carolina. Methods We analyzed surveillance drug resistance mutations (SDRMs) using partial pol sequences from patients presenting to 2 large HIV outpatient clinics from 1997 to 2014. Transmitted drug resistance prevalence was defined as ≥1 SDRMs among antiretroviral therapy (ART)–naïve patients. Binomial regression was used to characterize prevalence by calendar year, drug class, and demographic and clinical factors. We assessed the transmission networks of patients with TDR with maximum likelihood trees and Bayesian methods including background pol sequences (n = 15 246). Results Among 1658 patients with pretherapy resistance testing, ≥1 SDRMs was identified in 199 patients, with an aggregate TDR prevalence of 12% (95% confidence interval, 10% to 14%) increasing over time (P = .02). Resistance to non-nucleoside reverse transcriptase inhibitors (NNRTIs; 8%) was common, followed by nucleoside reverse transcriptase inhibitors (4%) and protease inhibitors (2%). Factors associated with TDR were being a man reporting sex with men, white race, young age, higher CD4 cell count, and being a member of a transmission cluster. Transmitted drug resistance was identified in 106 clusters ranging from 2 to 26 members. Cluster resistance was primarily NNRTI and dominated by ART-naïve patients or those with unknown ART initiation. Conclusions Moderate TDR prevalence persists in North Carolina, predominantly driven by NNRTI resistance. Most TDR cases were identified in transmission clusters, signifying multiple local transmission networks and TDR circulation among ART-naïve persons. Transmitted drug resistance surveillance can detect transmission networks and identify patients for enhanced services to promote early treatment.

Health Care Utilization Behaviors Predict Disengagement From HIV Care: A Latent Class Analysis

Abstract Background The traditional definition of engagement in HIV care in terms of only clinic attendance and viral suppression provides a limited understanding of how persons living with HIV (PLWH) interact with the health care system. Methods We conducted a retrospective analysis of patients with ≥1 HIV clinic visits at the Duke Adult Infectious Diseases Clinic between 2008 and 2013. Health care utilization was characterized by 4 indicators: clinic attendance in each half of the year (yes/no), number of emergency department (ED) visits/year (0, 1, or 2+), inpatient admissions/year (0, 1, 2+), and viral suppression (never, intermittent, always). Health care engagement patterns were modeled using latent class/latent transition analysis. Results.  A total of 2288 patients (median age, 46.4 years; 59% black, 71% male) were included in the analysis. Three care engagement classes were derived from the latent class model: “adherent” “nonadherent,” and “sick.” Patients age ≤40 years were more likely to be in the nonadherent class (odds ratio, 2.64; 95% confidence interval, 1.38–5.04) than other cohort members. Whites and males were more likely to transition from nonadherent to adherent the following year. Nonadherent patients were significantly more likely to disengage from care the subsequent year than adherent patients (23.6 vs 0.2%, P < .001). Conclusions A broader definition of health care engagement revealed distinct and dynamic patterns among PLWH that would have been hidden had only previous HIV clinic attendance had been considered. These patterns may be useful for designing engagement-targeted interventions.

Determinants of Left Ventricular Hypertrophy and Diastolic Dysfunction in an HIV Clinical Cohort

OBJECTIVE The aim of this work was to investigate determinants of structural myocardial abnormalities in persons living with human immunodeficiency virus (PLWH). METHODS AND RESULTS We reviewed archived transthoracic echocardiograms (TTEs) performed on PLWH at Duke University Medical Center from 2001 to 2012. The primary outcomes were presence of left ventricular hypertrophy (LVH) or diastolic dysfunction (DD). TTEs for 498 human immunodeficiency virus-infected persons were reviewed (median age 44 years, 38% female, 72% black, 34% with hypertension, 15% with diabetes). Among those with usable images, LVH was detected in 174 of 473 persons (37%) according to LV mass criteria and in 99 of 322 persons (31%) according to American Society of Echocardiography LV mass index criteria. Definite DD was detected in 18 of 224 persons (8%). LVH was more common in PLWH with a CD4 count ≤ 200 cells/mm3 proximal to TTE (adjusted OR 1.68, 95% CI 1.08-2.62), CD4 nadir ≤ 200 cells/mm3 (adjusted OR 1.63, 95% CI 1.04-2.54) and less common in persons with viral suppression (OR 0.46, 95% CI 0.27-0.80). Lower CD4 nadirs (P = .002) and proximal CD4 counts (P = .002) were also associated with DD. CONCLUSIONS Persons with a history of advanced human immunodeficiency virus-associated immune suppression are at higher risk of LVH and DD than infected persons with preserved immune function.