Publications

INTRODUCTION

At the individual level, there is clear evidence that Human Immunodeficiency Virus (HIV) transmission can be substantially reduced by lowering viral load. However there are few data describing population-level HIV viremia especially in high-burden settings with substantial under-diagnosis of HIV infection. The 2nd Kenya AIDS Indicator Survey (KAIS 2012) provided a unique opportunity to evaluate the impact of antiretroviral therapy (ART) coverage on viremia and to examine the risks for failure to suppress viral replication. We report population-level HIV viral load suppression using data from KAIS 2012.

METHODS

Between October 2012 to February 2013, KAIS 2012 surveyed household members, administered questionnaires and drew serum samples to test for HIV and, for those found to be infected with HIV, plasma viral load (PVL) was measured. Our principal outcome was unsuppressed HIV viremia, defined as a PVL ≥ 550 copies/mL. The exposure variables included current treatment with ART, prior history of an HIV diagnosis, and engagement in HIV care. All point estimates were adjusted to account for the KAIS 2012 cluster sampling design and survey non-response.

RESULTS

Overall, 61·2% (95% CI: 56·4-66·1) of HIV-infected Kenyans aged 15-64 years had not achieved virological suppression. The base10 median (interquartile range [IQR]) and mean (95% CI) VL was 4,633 copies/mL (0-51,596) and 81,750 copies/mL (59,366-104,134), respectively. Among 266 persons taking ART, 26.1% (95% CI: 20.0-32.1) had detectable viremia. Non-ART use, younger age, and lack of awareness of HIV status were independently associated with significantly higher odds of detectable viral load. In multivariate analysis for the sub-sample of patients on ART, detectable viremia was independently associated with younger age and sub-optimal adherence to ART.

DISCUSSION

This report adds to the limited data of nationally-representative surveys to report population- level virological suppression. We established heterogeneity across the ten administrative and HIV programmatic regions on levels of detectable viral load. Timely initiation of ART and retention in care are crucial for the elimination of transmission of HIV through sex, needle and syringe use or from mother to child. Further refinement of geospatial mapping of populations with highest risk of transmission is necessary.

BACKGROUND

Tuberculosis (TB) is the leading cause of death from an infectious pathogen worldwide and the most prevalent opportunistic infection in people living with HIV. Isoniazid preventive therapy (IPT) reduces the incidence of active TB and reduces morbidity and mortality in HIV-infected patients independently of antiretroviral therapy. However, treatment of latent or active TB is lengthy and inter-patient variability in pharmacokinetics and adherence common. Current methods of assessing adherence to TB treatment using drug levels in plasma or urine assess short-term exposure and pose logistical challenges. Drug concentrations in hair assess long-term exposure and have demonstrated pharmacodynamic relevance in HIV.

METHODS

A large hair sample from a patient with active TB was obtained for assay development. Methods to pulverize hair and extract isoniazid were optimized and then the drug detected by liquid chromatography/ tandem mass spectrometry (LC/MS-MS). The method was validated for specificity, accuracy, precision, recovery, linearity and stability to establish the assay's suitability for therapeutic drug monitoring (TDM). Hair samples from patients on directly-observe isoniazid-based latent or active TB therapy from the San Francisco Department of Public Health TB clinic were then tested.

RESULTS

Our LC/MS-MS-based assay detected isoniazid in quantities as low as 0.02ng/mg using 10-25 strands hair. Concentrations in spiked samples demonstrated linearity from 0.05-50ng/mg. Assay precision and accuracy for spiked quality-control samples were high, with an overall recovery rate of 79.5%. In 18 patients with latent or active TB on treatment, isoniazid was detected across a wide linear dynamic range.

CONCLUSIONS

An LC-MS/MS-based assay to quantify isoniazid levels in hair with performance characteristics suitable for TDM was developed and validated. Hair concentrations of isoniazid assess long-term exposure and may be useful for monitoring adherence to latent or active TB treatment in the setting of HIV.

Dyspnea is a common chief complaint in the emergency department, with over 4 million visits annually in the US. Establishing the correct diagnosis can be challenging, because the subjective sensation of dyspnea can result from a wide array of underlying pathology, including pulmonary, cardiac, neurologic, psychiatric, toxic, and metabolic disorders. Further, the presence of dyspnea is linked with increased mortality in a variety of conditions, and misdiagnosis of the cause of dyspnea leads to poor patient-level outcomes. In combination with the history and physical, efficient, and focused use of laboratory studies, the various cardiopulmonary biomarkers can be useful in establishing the correct diagnosis and guiding treatment decisions in a timely manner. Use and interpretation of such tests must be guided by the clinical context, as well as an understanding of the current evidence supporting their use. This review discusses current standards and research regarding the use of established and emerging cardiopulmonary laboratory markers in the evaluation of acute dyspnea, focusing on recent evidence assessing the diagnostic and prognostic utility of various tests. These markers include brain natriuretic peptide (BNP) and N-terminal prohormone (NT-proBNP), mid-regional peptides proatrial NP and proadrenomedullin, cardiac troponins, D-dimer, soluble ST2, and galectin 3, and included is a discussion on the use of arterial and venous blood gases.

Physicians' ability to predict length of stay is understudied, particularly for patients with heart failure (HF) admissions. The objective of this prospective, observational cohort study was to measure the accuracy of inpatient physicians' predictions of length of stay at the time of admission of patients admitted to an academic tertiary care hospital with HF and to determine whether level of experience improves accuracy. The patients included 165 adults consecutively admitted with heart failure, about whom 415 predictions were made within 24 hours of admission. Mean and median lengths of stay were 10.9 and 8 days, respectively. The mean difference between predicted and actual length of stay was statistically significant for all groups: interns, -5.9 days (95% confidence interval [CI]: -8.2 to -3.6, P < 0.0001); residents, -4.3 days (95% CI: -6.0 to -2.7, P = 0.0001); attending cardiologists, -3.5 days (95% CI: -5.1 to -2.0, P < 0.0001). There were no differences in accuracy by level of experience (P = 0.61). Physicians, regardless of experience, underestimate length of stay of patients admitted with HF. Journal of Hospital Medicine 2016;11:642-645. © 2016 Society of Hospital Medicine.