Browsing by Author "Gruber, Joshua"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    P-481. Characterization of People with HIV Who Are Virologically Suppressed with Treatment Experience Using a US Real-World Database
    (Oxford University Press, 2025-01-29) Gupta, Samir K.; Cappell, Katherine; Price, Kwanza; Bonafede, Mac; Gruber, Joshua; Mezzio, Dylan; Navadeh, Soodi; Sedgley, Robert; Segal-Maurer, Sorana; Medicine, School of Medicine
    Background: People living with HIV who are virologically suppressed with treatment experience (PWH-VSTE) are often prescribed complex multi-tablet and/or multi-dose antiretroviral (ARV) regimens with increased risk of poor clinical outcomes due to adherence challenges, adverse events, and/or drug interactions. This population is not well characterized, with no universal definition. We conducted a retrospective, observational analysis of a large US database to characterize PWH-VSTE and better understand this subset of PWH. Methods: PWH with treatment experience (PWH-TE) with ≥ 2 ARV lines of therapy (LOT) were identified from the Veradigm Network electronic health record (EHR) database linked with claims during the study period, Jan 2015–Dec 2022. We defined VSTE as virologic suppression (HIV-1 RNA ≤ 200 copies/mL) during the LOT in which ≥ 1 of the following treatment criteria were met: (1) used ≥ 1 “complex” ARV regimen; (2) resistance to exactly 2 ARV classes out of nucleoside or non-nucleoside reverse transcriptase inhibitors (NRTI, NNRTI), integrase strand transfer inhibitor (INSTI), and protease inhibitor (PI); (3) prior exposure to exactly 2 ARV classes out of NNRTI, INSTI, and PI (Figure). For inclusion, PWH-VSTE were aged ≥ 18 years and had an HIV diagnosis, continuous claims enrollment, and EHR activity. We report the proportion of PWH-TE meeting VSTE-defining criteria, and their characteristics. Results: Of 308,088 PWH-TE, 13,192 (4%) met ≥ 1 VSTE-defining criterion (9957 met Criterion 1 and 8272 met Criterion 3); 6907 (52%) were eligible for analysis (Figure). PWH-VSTE were mostly male (71%), Black (41%), aged 50–59 years (36%), using Medicaid (55%), from the South (39%), and had a mean (SD) Charlson Comorbidity Index of 6.1 (2.6) (Table). Among those with data during the baseline period (6-month period prior to index date), 48.2% (990/2052) had a viral load of ≤ 200 copies/mL. Resistance testing was done for 13.3% of PWH-VSTE during the baseline period, but only 0.2% had results available. Conclusion: In this large, real-world database, PWH-VSTE comprised 4% of PWH-TE, were mostly male, and had a high level of comorbidities. Understanding the characteristics of PWH-VSTE will enable clinicians to better address the needs of this historically understudied population.
  • Thumbnail Image
    Item
    Prescribing Prevalence of Medications With Potential Genotype-Guided Dosing in Pediatric Patients
    (American Medical Association, 2020-12) Ramsey, Laura B.; Ong, Henry H.; Schildcrout, Jonathan S.; Shi, Yaping; Tang, Leigh Anne; Hicks, J. Kevin; El Rouby, Nihal; Cavallari, Larisa H.; Tuteja, Sony; Aquilante, Christina L.; Beitelshees, Amber L.; Lemkin, Daniel L.; Blake, Kathryn V.; Williams, Helen; Cimino, James J.; Davis, Brittney H.; Limdi, Nita A.; Empey, Philip E.; Horvat, Christopher M.; Kao, David P.; Lipori, Gloria P.; Rosenman, Marc B.; Skaar, Todd C.; Teal, Evgenia; Winterstein, Almut G.; Obeng, Aniwaa Owusu; Salyakina, Daria; Gupta, Apeksha; Gruber, Joshua; McCafferty-Fernandez, Jennifer; Bishop, Jeffrey R.; Rivers, Zach; Benner, Ashley; Tamraz, Bani; Long-Boyle, Janel; Peterson, Josh F.; Van Driest, Sara L.; Pediatrics, School of Medicine
    Importance: Genotype-guided prescribing in pediatrics could prevent adverse drug reactions and improve therapeutic response. Clinical pharmacogenetic implementation guidelines are available for many medications commonly prescribed to children. Frequencies of medication prescription and actionable genotypes (genotypes where a prescribing change may be indicated) inform the potential value of pharmacogenetic implementation. Objective: To assess potential opportunities for genotype-guided prescribing in pediatric populations among multiple health systems by examining the prevalence of prescriptions for each drug with the highest level of evidence (Clinical Pharmacogenetics Implementation Consortium level A) and estimating the prevalence of potential actionable prescribing decisions. Design, setting, and participants: This serial cross-sectional study of prescribing prevalences in 16 health systems included electronic health records data from pediatric inpatient and outpatient encounters from January 1, 2011, to December 31, 2017. The health systems included academic medical centers with free-standing children's hospitals and community hospitals that were part of an adult health care system. Participants included approximately 2.9 million patients younger than 21 years observed per year. Data were analyzed from June 5, 2018, to April 14, 2020. Exposures: Prescription of 38 level A medications based on electronic health records. Main outcomes and measures: Annual prevalence of level A medication prescribing and estimated actionable exposures, calculated by combining estimated site-year prevalences across sites with each site weighted equally. Results: Data from approximately 2.9 million pediatric patients (median age, 8 [interquartile range, 2-16] years; 50.7% female, 62.3% White) were analyzed for a typical calendar year. The annual prescribing prevalence of at least 1 level A drug ranged from 7987 to 10 629 per 100 000 patients with increasing trends from 2011 to 2014. The most prescribed level A drug was the antiemetic ondansetron (annual prevalence of exposure, 8107 [95% CI, 8077-8137] per 100 000 children). Among commonly prescribed opioids, annual prevalence per 100 000 patients was 295 (95% CI, 273-317) for tramadol, 571 (95% CI, 557-586) for codeine, and 2116 (95% CI, 2097-2135) for oxycodone. The antidepressants citalopram, escitalopram, and amitriptyline were also commonly prescribed (annual prevalence, approximately 250 per 100 000 patients for each). Estimated prevalences of actionable exposures were highest for oxycodone and ondansetron (>300 per 100 000 patients annually). CYP2D6 and CYP2C19 substrates were more frequently prescribed than medications influenced by other genes. Conclusions and relevance: These findings suggest that opportunities for pharmacogenetic implementation among pediatric patients in the US are abundant. As expected, the greatest opportunity exists with implementing CYP2D6 and CYP2C19 pharmacogenetic guidance for commonly prescribed antiemetics, analgesics, and antidepressants.