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.

Association Between Proton Pump Inhibitors and Microscopic Colitis.

OBJECTIVE: Microscopic colitis (MC) is a chronic inflammatory disease of the colon that is characterized by chronic, watery, nonbloody diarrhea. Concern regarding a potential association between proton-pump inhibitors (PPIs) and MC has recently emerged. We sought to systematically review and summarize the evidence for the potential association between PPIs and MC. DATA SOURCES: We systematically searched EMBASE, MEDLINE, Cochrane Database of Systematic Reviews, International Pharmaceutical Abstracts, and Google Scholar using the terms proton-pump inhibitors (omeprazole, lansoprazole, dexlansoprazole, rabeprazole, pantoprazole, or esomeprazole), microscopic colitis, collagenous colitis, and lymphocytic colitis. STUDY SELECTION: Full-text, English-language reports of case reports/series, observational studies, experimental studies, and systematic reviews/meta-analyses published between January 2000 to August 2016 were included. Bibliographies from pertinent publications were reviewed for additional references. Outcome was defined as the development of biopsy-confirmed MC. DATA EXTRACTION/SYNTHESIS: A total of 19 publications were identified: 5 case control studies and 14 case reports/series (encompassing a total of 32 cases). All studies were limited by small sample sizes. Risk of MC by dose or specific PPI agent was not investigated in any of the studies. A review of the current body of evidence reveals a possible association between PPIs and MC. CONCLUSIONS: There is a need for large observational studies of high quality to examine the differential effect of specific PPIs and whether the magnitude of association is dose dependent. Given their widespread use, clinicians should routinely question whether patients are receiving unnecessary treatment with PPIs and discontinue therapy where appropriate.

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.

Improved virologic suppression with HIV subspecialty care in a large prison system using telemedicine: an observational study with historical controls.

Correctional populations have an elevated human immunodeficiency virus (HIV) prevalence, yet many individuals lack access to subspecialty care. Our study showed that HIV-infected inmates had significantly greater virologic suppression and higher CD4 T-lymphocyte counts when managed by a multidisciplinary team of subspecialists conducting clinics via telemedicine. In other studies, these outcomes have been associated with reductions on HIV-related morbidity and mortality, as well as HIV transmission.

Real-world prevalence of integrase inhibitor resistance and virological failure since adoption as guideline-preferred therapy.

Background: Limited data reporting real-world prevalence of integrase strand transfer inhibitor resistance (INSTI-R) in the USA are available because their recommendation as first-line treatment in 2017. Reported national surveillance data in the USA estimated INSTI-R to be 6.3% as of 2018. This article aims to describe estimated prevalence of INSTI-R within a single clinic network in Chicago, IL, USA, and identify risk factors for resistance and virological failure (VF). Methods: This was a retrospective, single-centre study of adults with HIV starting an INSTI-containing regimen between September 2017 and 2020. The primary endpoint was the difference in INSTI-R of the sample population compared with the national prevalence. Other outcomes included VF and documented INSTI-R mutations. Results: Of 948 participants screened, 321 were included. Eight people had baseline INSTI-R testing results available, of which five had INSTI-R at baseline for an estimated prevalence of 1.6%. This estimation was significantly less than the national estimated prevalence of 6.3% (p<0.001). VF occurred in 26 (7.8%) individuals. Because no participants acquired INSTI-R during the study period, investigators were unable to identify risk factors associated with the development of INSTI-R. People with high pre-treatment viral loads had 1.21 (95% CI 1.05-1.39) higher odds of VF. Conclusions: Amongst participants on INSTI-containing regimens, INSTI-R rates were estimated to be lower than the estimated national prevalence. Detectable pre-switch viral loads were more associated with VF than undetectable viral loads.

Virologic outcomes of antiretroviral therapy in patients with HIV-1 following bariatric surgery: A case series and review of the literature.

BACKGROUND: Selection of an antiretroviral regimen for people living with HIV (PLWH) involves various clinical considerations, such as comorbidities, archived drug resistance mutations, concomitant medications, and potential drug interactions and side effects. Alterations in the surface area and pH of the gastrointestinal tract following bariatric surgery may alter absorption, antiretroviral pharmacokinetics and viral suppression. Data on the efficacy of antiretroviral (ARV) therapy in PLWH who have undergone bariatric surgery are limited or lacking for new antiretrovirals, such as dolutegravir and bictegravir. METHODS: This case series reports virologic outcomes and side effects in eight cases of PLWH receiving ARV therapy who underwent bariatric surgery. A systematic literature review was performed to review the available literature on the efficacy and safety of antiretroviral regimens in PLWH who have undergone bariatric surgery. RESULTS: Virologic suppression was not impacted for obese PLWH who underwent bariatric surgery following failure of life-style modifications and pharmacological therapy. CONCLUSIONS: There were no deleterious effects on HIV progression for PLWH that underwent bariatric surgery. More prospective research is required to validate the effects of bariatric surgery on immunologic and virologic function outcomes. Close involvement of HIV and surgical specialists is recommended to manage ARV therapy in patients undergoing bariatric surgery.

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.

Consensus recommendations for use of long-acting antiretroviral medications in the treatment and prevention of HIV-1: Endorsed by the American Academy of HIV Medicine, American College of Clinical Pharmacy, Canadian HIV and Viral Hepatitis Pharmacists Network, European AIDS Clinical Society, and Society of Infectious Diseases Pharmacists: An executive summary.

Five long-acting (LA) antiretrovirals (ARVs) are currently available in a limited number of countries worldwide for HIV-1 prevention or treatment - cabotegravir, rilpivirine, lenacapavir, ibalizumab, and dapivirine. Implementing use of LA ARVs in routine clinical practice requires significant changes to the current framework of HIV-1 prevention, treatment, and service provision. Given the novelty, complexity, and interdisciplinary requirements of safe and optimal use of LA ARVs, consensus recommendations on the use of LA ARVs will assist clinicians in optimizing use of these agents. The purpose of these recommendations is to provide guidance for the clinical use of LA ARVs for HIV-1 treatment and prevention. In addition, future areas of research are identified and discussed.

Consensus recommendations for use of long-acting antiretroviral medications in the treatment and prevention of HIV-1: Endorsed by the American Academy of HIV Medicine, American College of Clinical Pharmacy, Canadian HIV and Viral Hepatitis Pharmacists Network, European AIDS Clinical Society, and Society of Infectious Diseases Pharmacists.

Five long-acting (LA) antiretrovirals (ARVs) are currently available in a limited number of countries worldwide for HIV-1 prevention or treatment-cabotegravir, rilpivirine, lenacapavir, ibalizumab, and dapivirine. Implementing use of LA ARVs into routine clinical practice requires significant changes to the current framework of HIV-1 prevention, treatment, and service provision. Given the novelty, complexity, and interdisciplinary requirements needed to safely and optimally utilize LA ARVs, consensus recommendations on the use of LA ARVs will assist clinicians in optimizing use of these agents. The purpose of these recommendations is to provide guidance for the clinical use of LA ARVs for HIV-1 treatment and prevention. In addition, future areas of research are also identified and discussed.

Bictegravir/Emtricitabine/Tenofovir Alafenamide for HIV-1: What is the Hidden Potential of This Emerging Treatment?

Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) is a single-tablet antiretroviral therapy regimen. B/F/TAF has become a popular treatment choice because of its small tablet size, high barrier to resistance, favorable tolerability, and limited drug-drug interaction profile. Continued research on B/F/TAF has revealed additional potential for this regimen. This review presents recent literature supporting the use of B/F/TAF as an option for consolidating therapy and maintaining virologic suppression in individuals despite M184V/I mutations. Additionally, children are a unique patient population with limited antiviral options. Standard dose B/F/TAF has demonstrated similar drug exposure in children and adolescents as adults, and low-dose B/F/TAF is approved for children living with HIV greater than two years of age and weighing at least 14 kg. Data supporting this recommendation is described in this review. Finally, despite a lack of prospective data, B/F/TAF may have a role in the future of pre- and post-exposure prophylaxis. This review discusses these discoveries and the continued exploration of the hidden potential of B/F/TAF.

A Systematic Review: Impact of SARS-CoV-2 Infection on Morbidity, Mortality, and Viral Suppression in Patients Living With HIV.

People living with HIV (PLWH) are a vulnerable patient population due to their immunosuppressed state and the risks associated with interruptions in treatment. After the unprecedented start of the COVID-19 pandemic, PLWH experienced complications involving interruptions in care and treatment, potentially leading to adverse outcomes including reduced rates of viral suppression, increased hospitalizations, and death. A systematic, comprehensive literature search was completed using PubMed, Google Scholar, and bibliography review to identify relevant articles related to clinical outcomes of HIV and SARS-CoV-2 co-infection. Related keywords were used as search terms: "COVID", "SARS-CoV-2", "coronavirus", "HIV", "viral load", "viral suppression", and "disease severity". Of the 492 results, 7 systematic reviews and 14 individual studies were included in the current review of literature regarding COVID-19-related outcomes in PLWH. In total, 2 systematic reviews and 8 individual studies found an increased rate of mortality, hospitalizations, and/or severe COVID-19 outcomes in PLWH co-infected with SARS-CoV-2, whereas the other 5 systematic reviews and 6 individual studies concluded PLWH were not at an increased risk compared to patients without HIV. Regarding viral suppression, 4 of 5 studies found viral suppression in PLWH was not impacted by the COVID-19 pandemic. The current literature suggests that the morbidity and mortality associated with SARS-CoV-2 infection in PLWH is complex and involves multiple factors including age and comorbid conditions; however, there is no clear consensus thus far. In contrast, literature consistently demonstrates that viral suppression during the pandemic has remained unchanged, potentially due to increased implementation of telemedicine and multicomponent interventions deployed.

How to design and implement an outpatient antimicrobial stewardship programme.

Antimicrobial stewardship programmes in the outpatient setting have recently become an area of focus in an effort to improve antimicrobial prescribing. The Centers for Disease Control and Prevention and The Joint Commission have recently addressed this concern and provided a framework for the implementation of an outpatient stewardship programme. This manuscript offers detailed guidance on how to design and implement an outpatient antimicrobial stewardship programme and reviews the literature on current strategies. Challenges related to initiating and maintaining outpatient stewardship efforts are also discussed. This article is part of the Antibiotic stewardship Special Issue: https://www.drugsincontext.com/special_issues/antimicrobial-stewardship-a-focus-on-the-need-for-moderation.

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.

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.

Evaluation of Immunologic and Virologic Function in Reincarcerated Patients Living With HIV or AIDS.

Despite receipt of antiretroviral therapy (ART) while incarcerated, formerly incarcerated individuals living with HIV may experience numerous barriers to follow-up HIV care and continuation of ART once released from prison. The goal of this retrospective electronic medical chart review was to determine virologic and immunologic function of individuals living with HIV who were reincarcerated within the Illinois Department of Corrections. Of 200 patients reincarcerated during the study period, 167 met inclusion criteria. The rate of participants who were on ART and virologically suppressed decreased from 73% at time of release to 49.7% at time of reincarceration (p < .01). Of the 57 individuals who did not engage in follow-up, 39% were virologically suppressed at time of reincarceration. Despite virologic suppression while incarcerated, increased linkage, engagement, and retention in medical care upon release from prison is essential in maintaining virologic suppression.

HIV: how to manage low-level viraemia in people living with HIV.

Background: People living with HIV (PLWH) and receiving antiretroviral therapy (ART) have a goal of achieving and maintaining viral suppression; however, low-level viraemia (LLV) (HIV-RNA viral load levels of 50-999 copies/mL) persists in certain patients despite consistent medication adherence, lack of drug interactions and no genotypic resistance. This is a narrative review of the growing evidence of LLV in PLWH to determine risk factors and ART management strategies and to discuss the implications of LLV on the development of future virological failure. Methods: A systematic, comprehensive literature search was completed in the English language using PubMed, Google Scholar and bibliography review to gather information about LLV in PLWH between July 2014 and June 2021. The following keywords were used as search terms: "low-level viremia", "HIV", "viral blip", "intensification", "genotyping", "adherence" and "resistance." Results: Of 66 studies examined, 39 were analysed and included in this review. All trials included were published between 2014 and 2021. Eleven studies assessed risk factors for LLV. Identified risk factors were low CD4+ T cell nadir counts at baseline, higher baseline viral load measurements, medication non-adherence, non-nucleoside reverse transcriptase inhibitor use and others. Three studies assessed genotyping and concluded that the interpretation of both historical RNA genotype resistance testing and current proviral DNA genotype resistance testing in patients with LLV is appropriate. Seven studies were evaluated and determined that modifying or intensifying ART regimens resulted in decreased incidence of virological failure. Conclusion: This compilation of reviewed data gives a framework for the management of PLWH with LLV. Currently, there are no clear or definitive treatment directions for LLV provided in guidelines. Complicating this topic further is the unclear and varying definitions of LLV. Future research is needed on this topic but patients presenting with LLV should have their medication adherence assessed, drug interactions checked and ART intensified, where appropriate.

Telemedicine for HIV Care: Current Status and Future Prospects.

Due to the COVID-19 pandemic, the use of telemedicine has been highlighted, especially in specialties, such as the management of HIV. Recent data were reviewed between January 1, 2019 and March 20, 2021 by searching English language manuscripts for studies documenting clinical outcomes in HIV care and the patient experience. A PubMed, Google Scholar, and bibliography review based on the search terms "HIV," "telemedicine," and "telehealth" was conducted. Studies included in this analysis were comprised of adult patients living with HIV, receiving care for HIV via telemedicine with reported clinical outcomes or perceptions of using telemedicine in the management of their HIV care. Of the 179 studies identified, 12 met inclusion for this analysis. Only two studies provided data on clinical outcomes of HIV (virologic outcomes), one pre-pandemic and one during COVID-19. The study evaluating viral suppression during COVID-19 demonstrated lower rates of virologic suppression and lower rates of missed appointments when shelter-in-place orders were issued compared to before the start of the pandemic. The remaining studies focused on patient-related outcomes as they related to the usability and adoption of telehealth models. Many practices documented the benefits and limitations of telemedicine based on the rapid switch from traditional in-person clinics. Benefits included retention in care for patients who lived a far distance from clinic, privacy for patients not wanting to be seen attending an HIV clinic, and more flexibility in scheduling appointments. Some limitations included patients' access to technology, ability and willingness to use technology, and privacy of patients who are homeless and reside in a shelter where homelessness is 3 times greater in people living with HIV compared to the general population. Healthcare should be tailored to the individual patient by assessing their needs and limitations, particularly with patients who may be at risk for discontinuation of care, particularly in the homeless population. In addition, there are mixed data on factors such as age, sex, and race being limiting factors in willingness to use technology. From the studies reviewed, willingness to engage with technology did not differ by age, sex, or race but did differ by access and willingness to use technology. Greater limitations were access to appropriate devices for telemedicine and digital literacy. Although there have been difficulties with the switch to telemedicine in clinics during the COVID-19 pandemic, many patients have reported being satisfied with care and would be interested in continuing once the shelter-in-place order is lifted. Future studies should focus on the provision of HIV care using telemedicine beyond the pandemic and focus on ways to improve the telemedicine experience for the patient.

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.