Antiretroviral drug-drug interactions: A comparison of online drug interaction databases.

WHAT IS KNOWN AND OBJECTIVE: Antiretrovirals have a high drug interaction potential, which can lead to increased toxicity and/or decreased efficacy. Multiple databases are available to assess drug-drug interactions. The aim of our study was to compare interaction identification for commonly used ARVs and concomitant medications between six different online drug-drug interaction databases. COMMENT: This was a cross-sectional review using each of the following six databases: LexiComp®, Clinical Pharmacology®, Micromedex®, Epocrates®, University of Liverpool, and University of Toronto. Sixteen antiretroviral drugs and 100 of the DrugStats Database "Top 200 of 2019" list of medications were included. Each of the six databases identified a different number of actual or potential interactions. The number of interactions ranged from 211 to 283. WHAT IS NEW AND CONCLUSIONS: A variety of databases exist with inconsistent identification of actual or potential drug-drug interactions amongst them. It may be beneficial to cross-reference multiple databases prior to making decisions regarding patient care.

Mycobacterium conceptionense Pneumonitis in Patient with HIV/AIDS1.

Approximately 21 human cases of infection with Mycobacterium conceptionense have been reported. However, most cases were outside the United States, and optimal treatment remains uncertain. We report a case of M. conceptionense pneumonitis in a patient with HIV/AIDS in the United States. The patient was cured with azithromycin and doxycycline.

Engaging in Collaborative Research: Focus on the Pharmacy Practitioner.

Research offers an opportunity for investigators to explore unanswered questions, highlight best practices, and engage in collaboration. Clinical research can engage health care professionals to identify treatments or procedures to enhance patient care, quality of life, and outcomes. Research may also include experiences in a unique practice site or teaching methodology of trainees, staff, or patients. The goal of research is to improve individual patient care via dissemination of knowledge through publications. This article aims to highlight the importance of pharmacist-led research in the academic or community medical center and the need for resident-based research and mentorship for the integration of collaborative research and achievement of organizational goals.

Assessing Immunity to Hepatitis A and Hepatitis B Among Individuals in Custody Living With HIV.

Screening upon entry into prison for hepatitis A virus (HAV) and hepatitis B virus (HBV) provides an ideal public health opportunity to offer vaccination to individuals who are nonimmune. We conducted a retrospective review of HAV and HBV immunity among adults living with HIV in the Illinois Department of Corrections between January 1, 2019, and December 31, 2019. The primary objective was to assess rates of HAV and/or HBV immunity in individuals with HIV. In total, 436 people were included in the study. Of 425 patients who had data for HAV vaccination, 335 were immune. Of 421 patients who had data for HBV vaccination, 272 were immune. Of the 149 patients who were nonimmune to HBV, 22 had active HBV and 6 had an equivocal HBV surface antibody and negative HBV surface antigen. In total, 212 (52%) were immune to both HAV and HBV, and 31 (8%) had no immunity to either HAV or HBV. These data demonstrate an important opportunity to discuss and provide vaccination while in custody.

Long-acting injectable antiretroviral therapy: will it change the future of HIV treatment?

The treatment of human immunodeficiency virus (HIV) has greatly advanced over the past few decades from complex regimens, with high toxicities, multiple daily dosing, and incomplete viral suppression to more simplified, highly effective, daily oral regimens. Although these advancements greatly improved access and tolerability, the need for daily antiretroviral (ARV) administration remained until recently. With long-acting (LA) injectable ARV options emerging, patients may choose how they want to receive treatment. By eliminating the barrier of daily medication adherence, LA injectable ARV formulations have the potential to not only improve health outcomes for the individual, but also the community by reducing HIV transmission. At the time of this writing cabotegravir/rilpivirine (LA-CAB/RPV) is the only LA injectable ARV regimen approved as a complete regimen for the treatment of HIV in adults and adolescents (⩾35 kg and ⩾12 years of age) who are virologically suppressed. However, additional studies of LA-CAB/RPV in expanded populations, and of other LA ARVs, are underway. The goal of this article was to summarize clinical data and review pertinent clinical considerations for the use of LA-CAB/RPV in the management of HIV.

Commonly Reported Mosquito-Borne Viruses in the United States: A Primer for Pharmacists.

Mosquito-borne diseases are a public health concern. Pharmacists are often a patient's first stop for health information and may be asked questions regarding transmission, symptoms, and treatment of mosquito borne viruses (MBVs). The objective of this paper is to review transmission, geographic location, symptoms, diagnosis and treatment of MBVs. We discuss the following viruses with cases in the US in recent years: Dengue, West Nile, Chikungunya, LaCrosse Encephalitis, Eastern Equine Encephalitis Virus, and Zika. Prevention, including vaccines, and the impact of climate change are also discussed.

Personalizing prevention: Advances in pharmacotherapy for HIV prevention.

The HIV epidemic continues to pose a significant burden on the healthcare system. Although the incidence of annual new infections is decreasing, health disparities persist and most new infections remain concentrated into different racial, ethnic, and minority groups. Pre-exposure prophylaxis (PrEP), which involves those at high risk of acquiring HIV to take chronic medications to prevent acquisition of the virus, is key to preventing new HIV infections. The purpose of this article is to review medication therapies for PrEP and examine their role in personalizing PrEP in different patient populations. Additionally, new medications currently under development for PrEP are reviewed, as well as treatment as prevention (TasP) and post-exposure prophylaxis (PEP). There are currently four medications available for PrEP: the oral options of co-formulated emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) or emtricitabine/tenofovir alafenamide (FTC/TAF); injectable long-acting cabotegravir (CAB-LA); and the vaginal ring dapivirine (DPV-VR). FTC/TAF is not currently indicated for persons at risk for HIV through vaginal sex due to lack of studies, but trials are currently ongoing. DPV-VR is available in Zimbabwe and South Africa and has been endorsed by the World Health Organization but is not currently available in the United States. Several agents are also in development for use in PrEP: the novel long-acting injectable lenacapavir, a first-in-class capsid inhibitor, which has no cross-resistance to any existing HIV drug class; the subdermal implant islatravir, a first-in-class translocation inhibitor; and VRC01, a broadly neutralizing antibody (bnAb) which has been evaluated in proof-of-concept studies that may lead to the development of more potent bnAbs. Overall, PrEP is highly effective at preventing HIV infection in high-risk populations. Identifying optimal PrEP regimens in different patient populations is complex and must consider patient-specific factors and medication cost and access considerations. Lastly, providers should consider individual patient preferences with regard to prevention to improve access, retention in care, and adherence.

Evidence Regarding Rapid Initiation of Antiretroviral Therapy in Patients Living with HIV.

PURPOSE OF REVIEW: Rapid initiation of antiretroviral therapy (ART) is increasingly more common among clinics serving people living with human immunodeficiency virus (PLWH). It is recommended by major guidelines and is especially important in achieving the Getting to Zero (GTZ) goals by 2030. Patients should be offered the option to initiate ART as soon as possible, preferably at time of HIV diagnosis, with the goal of reducing transmission, morbidity, and mortality. RECENT FINDINGS: Three published randomized controlled trials, and several other observational, prospective, and retrospective studies, demonstrated superior rates of viral suppression (VS) with initiation of rapid ART compared to standard of care. Improved time to VS and retention in care were also observed. Based on the regimens studied, a tenofovir backbone combined with an integrase strand transfer inhibitor or protease inhibitor is recommended for rapid start initiation. Since ART is started earlier compared with standard of care, there is opportunity to achieve VS at a much faster rate, especially in the setting of starting on the day of diagnosis. What requires further evaluation is whether or not VS is sustained over time with quicker linkage and initiation of HIV care. SUMMARY: Initiating rapid ART in newly diagnosed PLWH provides a promising approach to achieving GTZ. When offered rapid ART, virologic suppression is improved compared to standard of care, which may reduce transmission and, ultimately, new HIV infections.

Vitamins, supplements and COVID-19: a review of currently available evidence.

BACKGROUND: In the midst of the COVID-19 pandemic, there has been an information overload of health data (both accurate and inaccurate) available to the public. With vitamins and supplements being readily accessible, many have turned to using them in an effort to combat the virus. The purpose of this review was to analyse clinical trials regarding vitamins and supplements for the treatment of COVID-19 infections. METHODS: Articles were identified through a literature search utilizing online databases and bibliographic review. RESULTS: A total of seven articles were identified for review. All articles evaluated the use of vitamins and supplements for the treatment of COVID-19. Drug therapies included oral vitamin D, intravenous and oral vitamin C, oral vitamin D/magnesium/vitamin B12, oral zinc, oral combination zinc/ascorbic acid, and intravenous alpha-lipoic acid. The end points of each study varied, including the Sequential Organ Failure Assessment score, mortality, rate of intensive care unit (ICU) admissions, negativity of COVID-19 tests, oxygen requirements, and symptom burden. CONCLUSION: Of the vitamins and supplements that were studied, vitamin D presented the most promising data demonstrating significant decreases in oxygen requirements, need for ICU treatment, SARS-CoV-2 RNA test positivity, and mortality. All of these benefits were exhibited in hospitalized patients. Other vitamins and supplements that were evaluated in studies did not demonstrate any statistically significant benefits. Common shortcomings of the articles included generally small sample sizes, varying sites of study (which could determine the virus variant), a lack of standard of care as background therapy, and utilization of doses that were higher than standard.

Weight Gain in Incarcerated Individuals Living With HIV After Switching to Integrase Strand Inhibitor-Based Therapy.

INTRODUCTION: Post-marketing data have demonstrated the potential for weight gain with integrase inhibitors (INSTI) use in antiretroviral (ART) therapy. METHODS: A medical chart review evaluated virologically suppressed adult prisoners living with HIV and on a non-INSTI regimen before switching or adding an INSTI. Primary outcome assessed average weight change; Secondary outcomes evaluated change in body mass index (BMI), fasting lipid panel, and development of hypertension. Statistical analysis included paired t-tests and descriptive statistics. RESULTS: Among 103 study participants, 95% were men with a median age of 44 years. Each INSTI was associated with an average weight increase of 4.3 kg (p < 0.025). Bictegravir and dolutegravir were also associated with significant increases in BMI, +1.4kg/m2 and +2.8kg/m2, respectively (p = 0.011 and p = 0.001). CONCLUSION: Patients receiving HIV care in a correctional setting and on INSTI-based treatments experienced weight gain and increases in BMI. Future research should focus on the mechanism of development and interventions to prevent weight gain.

The race to a COVID-19 vaccine: opportunities and challenges in development and distribution.

The unprecedented toll of severe acute respiratory syndrome coronavirus 2, the virus responsible for coronavirus 2019 disease (COVID-19), jumpstarted the race towards the development and distribution of effective treatment and prevention options. With an urgent need to slow viral transmission, lessen disease severity, and reduce mortality, biopharmaceutical companies rapidly began investigating potential COVID-19 vaccinations. While typical vaccine development can take upwards of 10-15 years, COVID-19 vaccines were developed in less than a year after the identification of COVID-19. To accomplish this feat, clinical development, manufacturing scale-up and distribution are occurring in parallel for the four COVID-19 vaccine front-runners. This remarkable opportunity will forever change the drug development process and would not be possible without tremendous dedication from the public and private sectors, researchers, and clinical trial volunteers. However, many challenges still lie ahead. Comprehensive plans for equitable vaccine education, distribution, administration and post-marketing surveillance must be implemented successfully to overcome vaccine hesitancy, supply-chain obstacles and healthcare provider shortages in an already overburdened healthcare system. We are moving forward at a remarkable pace but worldwide immunity through vaccination will take time to achieve. Thus, current prevention efforts of masking, hand hygiene and social distancing must remain in effect for the foreseeable future. We must remain diligent and not fatigue in our efforts. Ending the COVID-19 pandemic cannot rest on the promise of vaccination alone - it will require a continued, robust and multi-faceted approach to disease treatment and prevention.

Real-world impact of switching from tenofovir disoproxil fumarate to tenofovir alafenamide.

Although tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) have been evaluated in various clinical trials, limited safety and efficacy data exist in real-world settings. The goal of this retrospective analysis is to assess changes in virological suppression, immunological status, renal function, weight and body mass index (BMI) amongst people living with HIV who switched from a TDF-based to a TAF-based regimen. Of 130 patients included in the final analysis, 53 patients experienced an increase in their viral load upon switching from TDF to TAF therapy whilst 62 patients remained undetectable. For those who experienced a viral blip, 33 (62%) resuppressed by the time of last follow-up, 15 (28%) patients did not have additional labs beyond the last follow-up and concern for failure occurred in 5 (9%) patients. No differences in immunological function, renal function, weight or BMI were observed from before switching to the last follow-up. Although a loss of virological suppression was found upon switching to TAF at subsequent follow-up visits, resuppression ultimately occurred in most patients.

Multicenter point prevalence evaluation of the utilization and safety of drug therapies for COVID-19 at the onset of the pandemic timeline in the United States.

KEY POINTS: In a multicenter point-prevalence study, we found that the rate of supportive care was high; among those receiving COVID-19 drug therapies, adverse reactions occurred in 12% of patients. PURPOSE: There are currently no FDA-approved medications for the treatment of coronavirus disease 2019 (COVID-19). At the onset of the pandemic, off-label medication use was supported by limited or no clinical data. We sought to characterize experimental COVID-19 therapies and identify safety signals during this period. METHODS: We conducted a noninterventional, multicenter, point prevalence study of patients hospitalized with suspected/confirmed COVID-19. Clinical and treatment characteristics within a 24-hour window were evaluated in a random sample of up to 30 patients per site. The primary objective was to describe COVID-19-targeted therapies. The secondary objective was to describe adverse drug reactions (ADRs). RESULTS: A total of 352 patients treated for COVID-19 at 15 US hospitals From April 18 to May 8, 2020, were included in the study. Most patients were treated at academic medical centers (53.4%) or community hospitals (42.6%). Sixty-seven patients (19%) were receiving drug therapy in addition to supportive care. Drug therapies used included hydroxychloroquine (69%), remdesivir (10%), and interleukin-6 antagonists (9%). Five patients (7.5%) were receiving combination therapy. The rate of use of COVID-19-directed drug therapy was higher in patients with vs patients without a history of asthma (14.9% vs 7%, P = 0.037) and in patients enrolled in clinical trials (26.9% vs 3.2%, P < 0.001). Among those receiving drug therapy, 8 patients (12%) experienced an ADR, and ADRs were recognized at a higher rate in patients enrolled in clinical trials (62.5% vs 22%; odds ratio, 5.9; P = 0.028). CONCLUSION: While we observed high rates of supportive care for patients with COVID-19, we also found that ADRs were common among patients receiving drug therapy, including those enrolled in clinical trials. Comprehensive systems are needed to identify and mitigate ADRs associated with experimental COVID-19 treatments.

Can vitamins and/or supplements provide hope against coronavirus?

Severe acute respiratory syndrome coronavirus-2 (SARS-COV-2) quickly became a global pandemic and has been responsible, so far, for infecting 5.8 million and claiming the lives of more than 350,000. While certain medications initially garnered attention as potential treatment options, further studies failed to demonstrate great promise but did demonstrate the need to reduce the cytokine storm experienced by patients with this potentially life-threatening virus. Unfortunately, there is no cure on the horizon, but members of the medical community are beginning to evaluate the potential role of vitamins and supplements as potential treatment options or addition to other treatments. The goal of this narrative review is to evaluate current and ongoing clinical trials of vitamins and supplements, alone or in combination with each other or other therapies, for the treatment of coronavirus disease-2019 (COVID-19).

Antiretroviral Stewardship: A Review of Published Outcomes with Recommendations for Program Implementation.

Persons living with HIV (PLWHs) are at high risk for medication errors when hospitalized, but antiretroviral medications are not often evaluated by antimicrobial stewardship programs (ASPs) because they are not specifically discussed in the standards of practice. However, antiretroviral (ARV) stewardship programs (ARVSPs) have been shown to decrease medication error rates and improve other outcomes. The goal of this article is to review published literature on ARVSPs and provide guidance on key aspects of ARVSPs. A MEDLINE search using the term "antiretroviral stewardship" was conducted. Original research articles evaluating ARVSPs in hospitalized, adult PLWHs were included. Six original research articles evaluating unique inpatient ARVSPs met inclusion criteria. All 6 studies evaluating medication errors as the primary outcome found a significant reduction in errors in the postimplementation phase. Based on current standards for ASPs, we propose core elements for ARVSPs. Future organizational guidelines for antimicrobial stewardship should include official recommendations for ARV medications.

Impact of Pharmacist-Driven Antiretroviral Stewardship and Transitions of Care Interventions on Persons With Human Immunodeficiency Virus.

BACKGROUND: Persons with human immunodeficiency virus (HIV) experience high rates of medication-related errors when admitted to the inpatient setting. Data are lacking on the impact of a combined antiretroviral (ARV) stewardship and transitions of care (TOC) program. We investigated the impact of a pharmacist-driven ARV stewardship and TOC program in persons with HIV. METHODS: This was a retrospective, quasi-experimental analysis evaluating the impact of an HIV-trained clinical pharmacist on hospitalized persons with HIV. Patients included in the study were adults following up, or planning to follow up, at the University of Illinois (UI) outpatient clinics for HIV care and admitted to the University of Illinois Hospital. Data were collected between July 1, 2017 and December 31, 2017 for the preimplementation phase and between July 1, 2018 and December 31, 2018 for the postimplementation phase. Primary and secondary endpoints included medication error rates related to antiretroviral therapy (ART) and opportunistic infection (OI) medications, all-cause readmission rates, medication access at time of hospital discharge, and linkage to care rates. RESULTS: A total of 128 patients were included in the study: 60 in the preimplementation phase and 68 in the postimplementation phase. After the implementation of this program, medication error rates associated with ART and OI medications decreased from 17% (10 of 60) to 6% (4 of 68) (P = .051), 30-day all-cause readmission rates decreased significantly from 27% (16 of 60) to 12% (8 of 68) (P = .03), and linkage to care rates increased significantly from 78% (46 of 59) to 92% (61 of 66) (P = .02). CONCLUSIONS: A pharmacist-led ARV stewardship and TOC program improved overall care of persons with HIV through reduction in medication error rates, all-cause readmission rates, and an improvement in linkage to care rates.

Multicenter point-prevalence evaluation of the utilization and safety of drug therapies for COVID-19.

BACKGROUND: There are currently no FDA-approved medications for the treatment of COVID-19. At the onset of the pandemic, off-label medication use was supported by limited or no clinical data. We sought to characterize experimental COVID-19 therapies and identify safety signals during this period. METHODS: We conducted a non-interventional, multicenter, point prevalence study of patients hospitalized with suspected/confirmed COVID-19. Clinical and treatment characteristics within a 24-hour window were evaluated in a random sample of up to 30 patients per site. The primary objective was to describe COVID-19 targeted therapies. The secondary objective was to describe adverse drug reactions (ADRs). RESULTS: A total of 352 patients from 15 US hospitals were included. Most patients were treated at academic medical centers (53.4%) or community hospitals (42.6%). Sixty-seven patients (19%) were receiving drug therapy in addition to supportive care. Drug therapies included hydroxychloroquine (69%), remdesivir (10%), and interleukin-6 inhibitors (9%). Five patients (7.5%) were receiving combination therapy. Patients with a history of asthma (14.9% vs. 7%, p=0.037) and those enrolled in clinical trials (26.9% vs. 3.2%, p<0.001) were more likely to receive therapy. Among those receiving COVID-19 therapy, eight patients (12%) experienced an ADR, and ADRs were more commonly recognized in patients enrolled in clinical trials (62.5% vs 22%, OR=5.9, p=0.028). CONCLUSIONS: While we observed high rates of supportive care for patients with COVID-19, we also found that ADRs were common among patients receiving drug therapy including in clinical trials. Comprehensive systems are needed to identify and mitigate ADRs associated with experimental COVID-19 therapies.

Abacavir/lamivudine/dolutegravir single tablet regimen in patients with human immunodeficiency virus and end-stage renal disease on hemodialysis.

No single-tablet antiretroviral (ARV) regimens (STRs) are approved for patients with human immunodeficiency virus (HIV) and end-stage renal disease (ESRD) on hemodialysis (HD). Based on known pharmacokinetic (PK) properties, abacavir (ABC)/lamivudine (3TC)/dolutegravir (DTG) STR may represent a promising option. This case series presents the safety and efficacy of ABC/3TC/DTG STR in patients with HIV and ESRD on HD. Patients were included if they were HIV-positive, maintained on intermittent HD for ESRD, switched to an ARV regimen containing ABC/3TC/DTG, and had at least one set of virologic data before and after the switch. Average age (±standard deviation) was 59 (±8) years. The majority of patients were cis-gender male and non-Hispanic Black. Only one demonstrated clinically significant resistance at baseline. All were on multiple-tablet regimens prior to the switch. Five patients (83%) achieved undetectable HIV-RNA after the switch while only four patients (46%) were undetectable immediately prior. No decline in immune function was noted. ABC/3TC/DTG STR was well tolerated. Only one patient self-reported an adverse event (nausea), which resolved without drug discontinuation. Based on these data, it appears that ABC/3TC/DTG may be a safe and effective ARV-STR option for patients with HIV and ESRD on HD. A larger trial including a PK analysis is needed to confirm these findings.

Optimizing Antiretroviral Therapy in Treatment-Experienced Patients Living with HIV: A Critical Review of Switch and Simplification Strategies. An Opinion of the HIV Practice and Research Network of the American College of Clinical Pharmacy.

Simplifying or switching antiretroviral therapy (ART) in treatment-experienced people living with HIV (PLWH) may improve adherence, tolerability, toxicities, and/or drug-drug interactions. The purpose of this review is to critically evaluate the literature for efficacy and safety associated with switching or simplifying ART in treatment-experienced PLWH. A systematic literature search using MEDLINE was performed from January 1, 2010 to April 30, 2018. References within articles of interest, the Department of Health and Human Services guidelines, and conference abstracts were also reviewed. Switch/simplification strategies were categorized as those supported by high-level clinical evidence and those with emerging data. Rates of virologic suppression were noninferior for several switch/simplification strategies when compared to baseline ART. Potential for reducing adverse events was also seen. Additional evidence for some strategies, including most 2-drug regimens, is needed before they can be recommended.

Simplifying ARV Therapy in the Setting of Resistance.

PURPOSE OF REVIEW: HIV treatment simplification is typically indicated for virologically suppressed patients with no baseline resistance-associated mutations (RAMs) or prior virologic failure (VF) to the simplification regimen. Simplification can occur to minimize pill burden, toxicities, drug-drug interactions, or costs. As most studies for treatment simplification excluded patients with baseline RAMs or prior VF, this review is aimed to critically analyze data regarding treatment simplification in treatment-experienced patients. RECENT FINDINGS: Antiretroviral (ARV) regimens containing three-, two-, and one-drug(s) have been scarcely studied to assess virologic efficacy in treatment-experienced patients. Three-drug regimens with the most data and highest efficacy are with integrase strand transfer inhibitors (INSTIs). Regimens including dolutegravir (DTG) and bictegravir have been shown to maintain efficacy in patients with certain baseline RAMs. Dual therapy regimens include the use of DTG plus either lamivudine (3TC), rilpivirine (RPV), or other ARVs. None of these studies evaluated patients with baseline DTG resistance. Baseline RAMs to 3TC were not a predictor of VF in patients on DTG/3TC. Efficacy was seen with DTG/RPV; however, studies showed high rates of discontinuation. DTG plus boosted-protease inhibitors were studied in smaller but promising studies. Two small studies assessed the use of monotherapy with boosted darunavir or DTG, both showing virologic efficacy. Currently, three- and two-drug ARV regimens may be considered in this population with most studies evaluating the use of DTG and bictegravir without baseline INSTI RAMs. Future studies should include heavily treatment-experienced patients with a variety of baseline RAMs and a larger sample size.