Bani Tamraz

Objective: This article describes the implementation of preemptive clinical pharmacogenomics (PGx) testing linked to an automated clinical decision support (CDS) system delivering actionable PGx information to clinicians at the point of care at UCSF Health, a large Academic Medical Center. Methods: A multidisciplinary team developed the strategic vision for the PGx program. Drug–gene interactions of interest were compiled, and actionable alleles identified. A genotyping platform was selected and validated in-house. Following HIPAA protocols, genotype results were electronically transferred and stored in electronic health records (EHRs). CDS was developed and integrated with electronic prescribing. Results: We developed a customized PGx program for 56 medications and 15 genes. Two hundred thirty-three pharmacogenomic prescribing alerts and 15 pharmacogenomic testing prompts, approved by clinicians, were built into EHR to deliver actionable clinical PGx information to clinicians. Conclusions: Our multidisciplinary team successfully implemented preemptive PGx testing linked to point-of-care CDS to guide clinicians with precise medication decision-making.

Introduction: Advances in genomics are transforming clinical practice, but there are too few genetics professionals to meet increasing demand. Moreover, many nongeneticist clinicians feel unprepared to incorporate genetics into practice. This study assessed clinicians' unmet genomics educational needs at a single academic institution. Methods: Qualitative interviews with Department and Division leaders informed a survey distributed to all clinicians at the institution. Survey questions focused on current practices, confidence, and desired educational resources around genetics and genomics. Data were analyzed using descriptive statistics and Fisher exact tests. Results were shared with an expert panel of Genetics-Genomics Champions to help meet educational needs across specialties. Results: Of the 215 survey respondents, 72% were faculty, 24% were trainees, and 4% were clinical staff, representing 18 departments. Less than half felt confident using genetics in the clinic. About 81% desired more training, which did not differ by role (P = .27) or department (P = .98). The Genetics-Genomics Champions proposed delivering just-in-time content via e-consults, online materials, and departmental meetings. Discussion: This study highlights clinicians' need and desire for more genetics training. It also underscores the importance of consulting genetics-savvy clinicians to identify challenges and solutions for addressing cross-specialty genetics education needs.

Objective This paper describes the implementation of preemptive clinical pharmacogenomics (PGx) testing linked to an automated electronic clinical decision support (CDS) system delivering clinically actionable PGx information to clinicians at the point of care at UCSF Health. Methods A multidisciplinary team was assembled. The drug-gene interactions of interest were compiled. Actionable alleles for target genes were identified. A genotyping platform was selected and validated. Following HIPAA protocols, genotype results were electronically transferred and stored in APeX, the electronic health record. CDS was developed and integrated with electronic prescribing in the form of best practice advisory (BPA) and medication warnings (MW). Results We developed a customized clinical PGx program for 56 medications and 15 genes. 233 MWs and 15 BPAs approved by clinicians, built into APeX, deliver actionable clinical PGx information to clinicians. Conclusions Our multidisciplinary team successfully implemented opt-out, preemptive PGx testing linked to point-of-care electronic CDS to guide clinicians at UCSF Health.

Background: Polypharmacy, using five or more medications, may increase the risk of nonadherence to prescribed treatment. We aimed to identify the interrelationship between trajectories of adherence to antiretroviral therapy (ART) and polypharmacy. Methods: We included women with HIV (aged ≥ 18) enrolled in the Women’s Interagency HIV Study in the United States from 2014 to 2019. We used group-based trajectory modeling (GBTM) to identify trajectories of adherence to ART and polypharmacy and the dual GBTM to identify the interrelationship between adherence and polypharmacy. Results: Overall, 1,538 were eligible (median age of 49 years). GBTM analysis revealed five latent trajectories of adherence with 42% of women grouped in the consistently moderate trajectory. GBTM identified four polypharmacy trajectories with 45% categorized in the consistently low group. Conclusions: The joint model did not reveal any interrelationship between ART adherence and polypharmacy trajectories. Future research should consider examining the interrelationship between both variables using objective measures of adherence.

Background: Women with HIV (WHIV) in the United States face many challenges with adherence to antiretroviral therapy (ART), and suboptimal adherence often leads to virologic failure. This study aimed to determine the association between ART adherence trajectories and the risk of virologic failure. Methods: We included WHIV (aged 18 years or older) enrolled in the Women's Interagency HIV Study in the United States from April 2014 to September 2019 who had at least 2 consecutive measurements of HIV RNA and ≥3 measurements of self-reported adherence. Group-based trajectory modeling was used to identify adherence trajectories. Cox proportional hazard ratios were used to measure the association. Main Outcome Measure: Virologic failure was defined as HIV RNA ≥200 copies/mL at 2 consecutive visits. Results: We included 1437 WHIV (median age 49 years). Of all women, 173 (12.0%) experienced virologic failure. Four adherence trajectories were identified, namely “consistently high” (26.3%), “moderate increasing” (9.5%), “moderate decreasing” (30.6%), and “consistently low” (33.5%). Women in the consistently low adherence group consumed alcohol and experienced depression more than other groups. Compared with the “consistently high” trajectory, the risk of virologic failure was higher among women with “consistently low” [adjusted hazard ratio (aHR) 2.8; 95% confidence interval (CI): 1.6 to 4.9; P < 0.001] and “moderate decreasing” adherence trajectories (aHR 1.8; 95% CI: 1.0 to 3.2; P = 0.04), but it was similar to those with “moderate increasing” adherence trajectory (aHR 1.0; 95% CI: 0.4 to 2.5; P = 0.94). Conclusions: Adherence to ART remains a challenge among WHIV. Multilevel behavioral interventions to address poor adherence, alcohol consumption, and depression are needed.

Background: Many women with HIV (WWH) have suboptimal adherence to oral antiretroviral therapy (ART) due to multilevel barriers to HIV care access and retention. A long-acting injectable (LAI) version of ART was approved by the US Food and Drug Administration in January 2021 and has the potential to overcome many of these barriers by eliminating the need for daily pill taking. However, it may not be optimal for all WWH. It is critical to develop tools that facilitate patient-provider shared decision making about oral versus LAI ART modalities to promote women’s adherence and long-term HIV outcomes.Objective: This study will develop and pilot test a web-based patient decision aid called i.ART+support (i.ARTs). This decision aid aims to support shared decision making between WWH and their providers, and help women choose between oral and LAI HIV treatment.Methods: The study will occur in 3 phases. In phase 1, we will utilize a mixed methods approach to collect data from WWH and medical and social service providers to inform i.ARTs content. During phase 2, we will conduct focus groups with WWH and providers to refine i.ARTs content and develop the web-based decision aid. In phase 3, i.ARTs will be tested in a randomized controlled trial with 180 women in Miami, Florida, and assessed for feasibility, usability, and acceptability, as well as to evaluate the associations between receiving i.ARTs and viral suppression, ART pharmacy refills, and clinic attendance.Results: This study was funded in March 2021. Columbia University’s IRB approved the study protocols (approval number IRB-AAAT5314). Protocols for phase 1 interviews have been developed and interviews with service providers started in September 2021. We will apply for Clinicaltrials.gov registration prior to phase 3, which is when our first participant will be enrolled in the randomized controlled trial. This is anticipated to occur in April 2023.Conclusions: This study is the first to develop a web-based patient decision aid to support WWH choices between oral and LAI ART. Its strengths include the incorporation of both patient and provider perspectives, a mixed methods design, and implementation in a real-world clinical setting.International Registered Report Identifier (IRRID): DERR1-10.2196/35646

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Study Objective: To evaluate the association between use of methadone, other central nervous system ( CNS ) depressants, and QT c interval–prolonging medications and risk of mortality among human immunodeficiency virus ( HIV )‐infected and at‐risk HIV ‐uninfected women. Design: Multicenter, prospective, observational cohort study (Women's Interagency HIV Study [ WIHS ]). Participants: A total of 4150 women enrolled in the WIHS study between 1994 and 2014 who were infected (3119 women) or not infected (1031 women) with HIV . Measurements and Main Results: Data on medication utilization were collected from all study participants via interviewer‐administered surveys at 6‐month intervals (1994–2014). Mortality was confirmed by National Death Index data. With age defining the time scale for the analysis, Cox proportional hazards models were used to estimate hazard ratios ( HR s) for all‐cause mortality in HIV ‐infected and ‐uninfected women and non–acquired immunodeficiency syndrome ( AIDS ) deaths in HIV ‐infected women. A total of 1046 deaths were identified, of which 429 were considered non‐ AIDS deaths. Use of benzodiazepines, CNS depressants (excluding methadone), and number of medications with conditional QT c interval–prolonging effects were each associated with all‐cause mortality in multivariate models of HIV ‐infected women: hazard ratio ( HR ) 1.28, 95% confidence interval ( CI ) 1.01–1.60, p=0.037; HR 1.61, 95% CI 1.35–1.92, p+ cell count, renal function, hemoglobin and albumin levels, HIV treatment era, employment status, existence of depressive symptoms, ever use of injection drugs, and tobacco smoking. Of interest, use of CNS depressants (excluding methadone) was also associated with non‐ AIDS deaths ( HR 1.49, 95% CI 1.49–2.2, p0.05). Conclusion: In this cohort of HIV ‐infected and at‐risk HIV ‐uninfected women, use of benzodiazepines, CNS depressants, and conditional QT c interval–prolonging medications were associated with a higher risk of mortality independent of methadone and other well‐recognized mortality risk factors. Care must be taken to assess risk when prescribing these medications in this underserved and at‐risk patient population.

Introduction Genetic‐guided selection of non‐oncologic medications is not commonly practiced in general, and at University of California, San Francisco (UCSF) Health, specifically. Understanding the unique position of clinicians with respect to clinical pharmacogenetics (PG) at a specific institution or practice is fundamental for implementing a successful PG consult service. Objectives To assess clinicians’ current practices, needs, and interests with respect to clinical PG at UCSF Health, a large tertiary academic medical center. Methods A list of 42 target medications with clinical PG recommendations was complied. Clinical specialties that routinely used the target medications were identified. A 12‐question survey focused on practice of PG for target medications was developed. Pharmacists and physicians were surveyed anonymously in several clinical specialties. Survey results were analyzed using descriptive statistics. Results Of the 396 clinicians surveyed, 76 physicians and 59 pharmacists participated, resulting in 27% and 50% average response rates, respectively. The current use of PG in clinical practice for physicians and pharmacists was 29% and 32%, respectively, however this number varied across clinical specialties from 0% to 80%. Of clinicians whom reported they do not currently apply PG, 63% of physicians and 54% of pharmacists expressed interest in integrating PG. However, the level of interest varied from 20% to 100% across specialties. Of the respondents, 64% of physicians and 56% of pharmacists elected to provide contact information to investigators to further discuss their interest related to clinical PG. Conclusions While PG is not uniformly practiced at UCSF Health, there is considerable interest in utilizing PG by the respondents. Our approach was successful at identifying clinicians and services interested in PG for specific drug‐gene pairs. This work has set a foundation for next steps to advance PG integration at UCSF Health. Clinicians can adopt our approach as preliminary work to build a clinical PG program at their institutions.