BACKGROUND

The antiretroviral medication, tenofovir disoproxil fumarate (TDF), is used by most human immunodeficiency virus-infected persons in the United States despite higher risks of chronic kidney disease. Although chronic kidney disease is a strong risk factor for heart failure (HF), the association of TDF with incident HF is unclear.

METHODS AND RESULTS

We identified 21 435 human immunodeficiency virus-infected patients in the United States Veterans Health Administration actively using antiretrovirals between 2002 and 2011. We excluded patients with a prior diagnosis of HF. TDF was analyzed categorically (current, past, or never use) and continuously (per year of use). Proportional hazards regression and fully adjusted marginal structural models were used to determine the association of TDF exposure with risk of incident HF after adjustment for demographic, human immunodeficiency virus-related, and cardiovascular risk factors. During follow-up, 438 incident HF events occurred. Unadjusted 5-year event rates for current, past, and never users of TDF were 0.9 (95%CI 0.7-1.1), 1.7 (1.4-2.2), and 4.5 (3.9-5.0), respectively. In fully adjusted analyses, HF risk was markedly lower in current TDF users (HR=0.68; 95%CI 0.53-0.86) compared with never users. Among current TDF users, each additional year of TDF exposure was associated with a 21% lower risk of incident HF (95%CI: 0.68-0.92). When limited to antiretroviral-naive patients, HF risk remained lower in current TDF users (HR=0.53; 95%CI 0.36-0.78) compared to never users.

CONCLUSIONS

Among a large national cohort of human immunodeficiency virus-infected patients, TDF use was strongly associated with lower risk of incident HF. These findings warrant confirmation in other populations, both with TDF and the recently approved tenofovir alafenamide fumarate.

Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death. Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups. To further define the genetic basis of atrial fibrillation, we performed large-scale, trans-ancestry meta-analyses of common and rare variant association studies. The genome-wide association studies (GWAS) included 17,931 individuals with atrial fibrillation and 115,142 referents; the exome-wide association studies (ExWAS) and rare variant association studies (RVAS) involved 22,346 cases and 132,086 referents. We identified 12 new genetic loci that exceeded genome-wide significance, implicating genes involved in cardiac electrical and structural remodeling. Our results nearly double the number of known genetic loci for atrial fibrillation, provide insights into the molecular basis of atrial fibrillation, and may facilitate the identification of new potential targets for drug discovery.

BACKGROUND

Urine biomarkers have helped identify persons at risk for progressing to kidney disease in the setting of HIV infection. We explored factors associated with changes in 3 urine biomarkers over 10 years among women living with HIV.

METHODS

Prospective cohort of 294 HIV-infected women from the multicenter Women's Interagency HIV Study. Predictors included HIV viral and immunological parameters, comorbid conditions, and health-related behaviors. Outcomes were patterns of changes of urine interleukin-18 (IL-18), albumin-to-creatinine ratio (ACR), and alpha-1-microglobulin (α1m) over 10 years. We used quantile regression to examine patterns of change in each urine biomarker during follow-up and multivariable analysis of variance regression to identify predictors of biomarker changes.

RESULTS

Over 10 years, the median concentrations of IL-18 declined from 120 to 64 pg/mL, α1m rose from 0.7 to 1.5 ng/mL, and ACR remained stable (9-8 mg/g). In multivariate analyses, the strongest predictors of increases in IL-18 were higher baseline body mass index, increase in waist circumference, higher follow-up HIV viral load, lower follow-up CD4 cell count, hepatitis C virus (HCV) coinfection, and higher follow-up high density lipoprotein cholesterol. Predictors of increasing concentration of α1m were lower CD4 cell counts, higher diastolic blood pressure, HCV coinfection, and smoking. Finally, determinants of ACR increases during follow-up were higher follow-up diastolic blood pressure, HCV coinfection, higher follow-up HIV viral load, and triglyceride concentration.

CONCLUSIONS

Over 10 years, HIV disease status had different associations with each urine biomarker under study. Overall, the associations with changes in each biomarker support research into their use for longitudinal monitoring of kidney health.

OBJECTIVE

In 2013, the American College of Rheumatology published its Choosing Wisely list, which identified 2 radiographic procedures (peripheral joint magnetic resonance imaging [MRI] and dual x-ray absorptiometry [DXA] scans) that were at risk for overuse.

METHODS

We performed a retrospective cross-sectional cohort study to measure the use of peripheral joint MRI, peripheral joint radiographs, and DXA scans in a national cohort of Medicare patients with rheumatoid arthritis (RA) during 2008-2009, before the start of the Choosing Wisely campaign. Diagnoses were identified via International Classification of Diseases, Ninth Revision, codes; utilization was calculated using Current Procedural Terminology codes. Utilization was analyzed at the individual level and at the regional level (by hospital referral region [HRR]).

RESULTS

There were 8,051 patients with RA who were included: 81% were women, and the mean age was 76 years. Over a 2-year period, the mean number of peripheral joint MRIs per beneficiary was 0.3 (median 0 [range 0-50]), peripheral joint radiographs per beneficiary was 2.6 (median 1 [range 0-33]), and DXA scans per beneficiary was 0.7 (median 0 [range 0-11]). Only 6.8% of patients received >1 peripheral joint MRI, and 6% of HRRs had a mean number of peripheral joint MRIs >1.

CONCLUSION

There is variation in the use of peripheral joint MRI, peripheral joint radiographs, and DXA scans among Medicare patients with RA, although only a small number of HRRs have consistently high utilization. Although we cannot judge the appropriateness of each procedure, variation in use across regions signals the need for investigations to examine potential overutilization.