Meredith E. Clement

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.

Syphilis on the Rise: What Went Wrong?

As the 1990s ended, syphilis was on the decline. At least in part due to safer sexual behaviors prompted by the AIDS epidemic,1 the rate of incident syphilis declined to fewer than 4 cases per 100 000 by the year 2000, a historic nadir. Eradication of Treponema pallidum infection in the United States seemed quite possible through concentrated public health efforts in a relatively small number of high-incidence US communities, and the Centers for Disease Control and Prevention (CDC) was developing a national syphilis elimination plan.2 Timing seemed auspicious for eradication efforts to be successful. Now, in 2016, hopes for eradication have long since faded, as have many of the gains realized by the effort. Rates of syphilis have trended steadily upward since 2000, and the CDC’s syphilis elimination efforts officially ended as of December 2013.

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.

Scedosporium apiosermum infection of the "Native" valve: Fungal endocarditis in an orthotopic heart transplant recipient.

Scedosporium apiospermum is an increasingly appreciated pathogen in immunosuppressed patients. We present a case of S. apiospermum endocarditis in a 70-year-old male who had undergone orthotopic heart transplant. Echocardiogram demonstrated a 1.4 cm tricuspid valve vegetation. He underwent valve replacement, complicated by fatal massive post-operative haemorrhage. Valve cultures grew S. apiospermum. To our knowledge, our case is the first reported instance of endocarditis caused by S. apiospermum in a recipient of a cardiac transplant.

An educational initiative in response to identified PrEP prescribing needs among PCPs in the Southern U.S.

ABSTRACT Pre-exposure prophylaxis (PrEP) is an effective HIV prevention method, but many primary care physicians (PCPs) have not incorporated PrEP into practice. While PrEP may be a key strategy to reducing high HIV transmission rates in the southern US, knowledge about PrEP prescribing patterns among PCPs in this region is lacking. An online survey was sent to a large network of PCPs at an academic medical center in North Carolina in October 2015. The survey was repeated in September 2016, after an educational intervention that included on-site trainings at 14 PCP offices. Chi-square tests were used to compare PrEP prescribing patterns among providers. The initial survey was sent to 389 PCPs, with 115 (30%) responding. Of these, 78% reported seeing men who have sex with men (MSM). Only 17% had prescribed PrEP. The most frequently identified barrier was lack of knowledge (60%). When the survey was repeated after the educational initiative, 79 PCPs (20%) responded. Of these, 90% reported seeing MSM, and 35% had prescribed PrEP. PCPs who had attended a training were more likely to have prescribed PrEP (OR 4.84, CI 1.77–13.21). In conclusion, PrEP prescribing among PCPs in the southern US is low. A survey among PCPs identified lack of knowledge as a barrier to prescribing, motivating an institutional-wide educational campaign in response. Further efforts are needed to continue to raise awareness and educate PCPs in the South about PrEP.

RPR and the Serologic Diagnosis of Syphilis

Clinical Review & Education JAMA Diagnostic Test Interpretation RPR and the Serologic Diagnosis of Syphilis Meredith E. Clement, MD; Charles B. Hicks, MD A 45-year-old man presents in clinic for follow-up after a recent emergency department evaluation for dysuria. He was diagnosed with gonococcal urethritis and treated with in- tramuscular ceftriaxone and oral azithromycin. His dysuria resolved and he now feels well. He was divorced 10 years previously and has since had multiple sexual partners. He re- ports sex only with women. His examination is normal, including the genitalia and skin. He has no neurologic deficits. Screening for other sexually transmitted infections reveals hepa- titis B virus serologies consistent with previous immunization, a negative human immuno- deficiency virus (HIV) enzyme immunoassay (EIA), and reactive syphilis test results (Table 1). The patient does not recall prior syphilis diagnosis or treatment. The local health de- partment has no record of syphilis testing for him. Table 1. Patient Test Results Laboratory Test Value Reference Range RPR Nonreactive TP-EIA Reactive Nonreactive Abbreviations: RPR, rapid plasma reagin; TP-EIA, Treponema pallidum enzyme immunoassay. HOW DO YOU INTERPRET THESE RESULTS? A. The patient has latent syphilis and requires 2.4 million U intramuscularly of benzathine penicillin G weekly for 3 doses (total 7.2 million U penicillin). B. The patient has low titers representing the serofast state and does not require treatment. C. The patient has falsely elevated titers and should undergo repeat testing. D. The patient needs a lumbar puncture to assess for asymptomatic neurosyphilis. Answer A. The patient has latent syphilis and requires 2.4 million U intra- muscularly of benzathine penicillin G weekly for 3 doses (total 7.2 million U penicillin). Test Characteristics A clear understanding of the diagnosis of syphilis is of particular pub- lic health importance because the incidence of syphilis in the United States is increasing. Currently, an estimated 55 000 new cases are diagnosed each year. 1 Treponema pallidum, the spirochete that causes syphilis, cannot be cultured. Thus, diagnosis requires indi- rect techniques such as serologic testing, relying on the detection of both treponemal and nontreponemal antibodies. Treponemal tests detect antibodies to specific antigenic components of T pall- idum, while nontreponemal tests detect antibodies to a nonspe- cific cardiolipin-cholesterol-lecithin reagin antigen produced by the host in response to syphilis infection. 2 The rapid plasma reagin (RPR), a nontreponemal test, has tra- ditionally been used as an initial screening test for syphilis because it is widely available, relatively easy to perform, and inexpensive (Medicare midpoint reimbursement, RPR with reflex titer,

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

8.11). 3 Additionally, RPR is a quantitative test and antibody titers can be monitored to assess treatment response. 4 However, the RPR re- quires a visual assessment for the presence of flocculation (aggre- gation of particles), a process that requires laboratory technologist time and is not suitable for automation. Furthermore, false- positive results may occur in the setting of autoimmune disease, pregnancy, tuberculosis, or other inflammatory conditions; thus, RPR testing requires confirmation with treponemal serologic tests such as the T pallidum enzyme immunoassay (TP-EIA). 5 Although false- positive results also occur with TP-EIA, it is unlikely that a patient will have both false-positive reagin and false-positive treponemal se- rologies. Therefore, the presence of a reactive nontreponemal test and a reactive treponemal test is diagnostic of syphilis (Table 2). 4,6,7 Application to This Patient This patient has late latent syphilis and should receive 3 weekly in- jections of benzathine penicillin G. Because the patient is asymptomatic with reactive serologies, he has latent syphilis. Latent syphilis can be divided into early- latent syphilis, diagnosed within 1 year of infection, and late-latent syphilis, diagnosed 1 year or more after infection. When the date of original infection is unknown, the patient is considered to have late- latent syphilis. 8,9 Early-latent syphilis is treated with a single intramuscular dose of benzathine penicillin G, while late-latent syphilis requires 3 weekly doses of benzathine penicillin G. 6 Following successful treatment, the RPR declines over time and may become nonreactive. However, the RPR may remain reactive at a low titer (generally <1:8), a condition referred to as the serofast state. The serofast state does not apply to this patient because he has no previous syphilis history. He does not have falsely elevated titers; his treponemal and nontreponemal tests were both reactive, making the diagnosis of syphilis and obviating the need for repeat testing. Because T pallidum can invade the central ner- JAMA November 12, 2014 Volume 312, Number 18 Copyright 2014 American Medical Association. All rights reserved. Downloaded From: http://jama.jamanetwork.com/ by a University of California - San Diego User on 09/01/2015 jama.com

Hepatitis C Virus Elimination in the Human Immunodeficiency Virus–Coinfected Population

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.

Incidence, Long-Term Outcomes, and Healthcare Utilization of Patients With Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome and Disseminated Mycobacterium avium Complex From 1992–2015

The objective of this review is to consider how existing human immunodeficiency virus (HIV) infrastructure may be leveraged to inform and improve hepatitis C virus (HCV) treatment efforts in the HIV-HCV coinfected population. Current gaps in HCV care relevant to the care continuum are reviewed. Successes in HIV treatment are then applied to the HCV treatment model for coinfected patients. Finally, the authors give examples of HCV treatment strategies for coinfected patients in both domestic and international settings.

Suboptimal HIV Testing Among Patients Admitted With Pneumonia: A Missed Opportunity

Abstract Background Despite the advent of combination antiretroviral therapy (cART), patients with human immunodeficiency virus (HIV) continue to develop late-stage complications including acquired immune deficiency syndrome (AIDS), disseminated Mycobacterium avium complex (DMAC), and death. Methods We performed an observational retrospective cohort study of HIV-infected adults who developed DMAC in the Duke University Health System from 1992 to 2015 to determine the incidence, long-term outcomes, and healthcare utilization of this population at high risk for poor outcomes. Findings were stratified by the “pre-cART” era (before January 1, 1996) and “post-cART” thereafter. Results We identified 330 adult HIV-infected patients newly diagnosed with DMAC, the majority (75.2%) of whom were male and non-Hispanic black (69.1%), with median age of 37 years. Incidence of DMAC declined significantly from 65.3/1000 in 1992 to 2.0/1000 in 2015, and the proportion of females and non-Hispanic blacks was significantly higher in the post-cART era. The standardized mortality ratios for DMAC patients who received cART were 69, 58, 27, 5.9, and 6.8 at years 1–5, respectively, after DMAC diagnosis. For patients diagnosed with DMAC in 2000 or later (n = 135), 20% were newly diagnosed with HIV in the 3 months preceding presentation with DMAC. Those with established HIV had a median time from HIV diagnosis to DMAC diagnosis of 7 years and were more likely to be black, rehospitalized in the 6 months after DMAC diagnosis, and die in the long term. Conclusions Disseminated Mycobacterium avium complex continues to be a lethal diagnosis in the cART era, disproportionately afflicts minority populations, and reflects both delayed entry into care and failure to consistently engage care.