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OBJECTIVES Despite an increased risk of atherosclerotic cardiovascular disease (ASCVD) in people living with HIV (PLWH), a gap in statin prescribing practices has been described for statin-eligble PLWH and uninfected patients. Few data have become available characterizing this gap since the publication of the 2013 American College of Cardiology/American Heart Association lipid guidelines. The objective of this study was to characterize statin prescribing rates for eligible PLWH compared to uninfected adults. METHODS This was a retrospective, comparative analysis of patients seen at two clinics in an urban, academic medical system between February 2017 and September 2017. Patients who qualified for one of the statin benefit groups were included: those with a history of clinical ASCVD, low-density lipoprotein cholesterol ≥ 190 mg/dL, diabetes mellitus, or 10-year ASCVD risk score ≥ 7.5%. Patients

Certain comorbidities known to increase the risk of poor outcomes in COVID-19 exist at higher rates in people with HIV; people aging with HIV (PAWH) face additional risk due to the association of advanced age with COVID-19 mortality. Cognitive and functional deficits and social barriers have been identified in cohorts of people aging with HIV. It is postulated that the COVID-19 pandemic potentially threatens PAWH disproportionately to the general population, both in mortality risk due to age and comorbidities, and in potential deleterious effects of policies that seek to drastically limit in-person interaction and access to healthcare systems. A description of and preliminary data from a demonstration project to improve geriatric assessments of people with HIV over age 50 in an urban HIV clinic are presented, in support of this theory. Advice is offered on key strategies utilized to continue to provide care to PAWH during the COVID-19 pandemic, including transition to telemedicine, vaccination, revision of staff roles, repurposing of funding, and a new reliance on available local resources.

This chapter opens with a discussion about classes and mechanisms of antiretroviral agents. The mechanisms of action of the traditional versus newer antiretroviral classes are reviewed as well as the five major categories of antiretroviral agents. Key characteristics and findings of recent clinical trials involving the regimens recommended by the US Department of Health and Human Services are reported. The chapter concludes with a discussion about what is on the horizon for antiretroviral therapy.

OBJECTIVES Patients living with HIV (PLWH) are predisposed to atherosclerotic cardiovascular disease (ASCVD), resulting in concomitant antiretroviral and statin use. A statin prescribing gap for PLWH has been reported, but appropriateness of statin selection and dosing (ASD) has not been described. METHODS This is a comparative, retrospective study reviewing ASD in PLWH vs. uninfected patients at two outpatient clinics within an academic medical centre. Adults > 21 years old indicated for statin therapy were included. The primary outcome was percentage of PLWH prescribed an appropriately dosed statin, accounting for clinical- and patient-related variables, compared with uninfected patients. The secondary outcome was to identify patient characteristics associated with inappropriately dosed statins. RESULTS After propensity score matching, 879 PLWH and 879 uninfected patients were included for analysis. Fewer PLWH (27.8%, n = 244) were prescribed an ASD compared with uninfected patients (40.5%, n = 356, P

Introduction In patients with hepatitis C virus (HCV), human immunodeficiency virus (HIV) represents a major cause of morbidity and economic burden. Economic evaluations in HIV-HCV typically focus on government-sponsored insurance plans rather than a commercially insured cohort. This study evaluated the clinical and economic burden of HIV-HCV co-infection compared with HCV alone in commercially insured patients throughout the United States. Methods Commercial medical and pharmacy claims from 2007 to 2015 from a 10% random sample of enrollees within the IQVIA PharMetrics Plus™ administrative claims database were analyzed. Patients were included based on the presence of a claim with a HCV diagnosis across three separate cross-sectional periods which were created from the full dataset (2007–2009, 2010–2012, and 2013–2015). Costs incurred were categorized as emergency department, inpatient, outpatient medical, outpatient pharmacy, and other, based on the claim place of service. Descriptive statistics and proportion of total costs in each group have been reported for all cost categories. Results The samples included 22,329 from 2007 to 2009, 23,186 from 2010 to 2012, and 27,288 from 2013 to 2015. In all three cross-sections, HIV-HCV individuals were more likely to be male and carriers of hepatitis B virus. Pharmacy costs were $29,368 in the HCV-only group, compared to $73,547 in the HIV-HCV group (p

Background Pharmacokinetic (PK) changes can affect antiretroviral (ARV) systemic exposure for critically ill patients living with HIV (CI-PLWH). Studies to guide ARV adjustments in this population are limited. Methods A PK analysis was conducted in a 44-year-old CI-PLWH who presented for a heart and lung transplant on veno-arterial extracorporeal membrane oxygenation (VA ECMO). Home ARV therapy (ART) of co-formulated abacavir/lamivudine/dolutegravir (ABC/3TC/DTG) was continued. ARV serum concentrations were obtained during and after VA ECMO. Two blood levels were drawn at 1 h, for maximum serum concentration (Cmax) and a serum trough (Ct). ARVs were given as a single tablet crushed via nasogastric tube. Results Area under the concentration–time curve (AUC0–t) was calculated using non-compartmental analysis. Cmax and AUC0–t were higher during VA ECMO compared with post-decannulation. The Cmax of ABC was >2.5-fold higher than the mean in the reference. Cmax and Ct post VA ECMO were within range of referenced literature for all ARVs. Cmax and AUC0–t of DTG post VA ECMO was approximately four- to fivefold lower than referenced literature. HIV virological suppression was maintained throughout the hospitalization. Conclusions ART adjustments would not be required for this patient. Additional studies are needed to assess effects of VA ECMO and crushed tube administration of ARVs in CI-PLWH.

BackgroundSwitching antiretroviral therapy (ART) in people with HIV (PWH) can influence their risk for drug–drug interactions (DDIs). The purpose of this study was to assess changes in the incidence and severity of DDIs among PWH who switched their ART to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF).MethodsThis was a multicenter retrospective cohort study of PWH on ART and at least 1 concomitant medication (CM) who switched to BIC/FTC/TAF between 3/2018 and 6/2019. Using the University of Liverpool’s HIV Drug Interaction Database, 2 DDI analyses were performed for each patient. The first assessed patients’ preswitch ART regimens with their CM list. The second assessed the same CM list with BIC/FTC/TAF. Each ART-CM combination was given a score of 0 (no or potential weak interaction), 1 (potential interaction), or 2 (contraindicated interaction). A paired t test analyzed changes in total DDI scores following ART switches, and linear regression examined factors contributing to DDI score reductions.ResultsAmong 411 patients, 236 (57%) had at least 1 DDI present at baseline. On average, baseline DDI scores (SD) were 1.4 (1.8) and decreased by 1 point (95% CI, –1.1 to –0.8) after patients switched to BIC/FTC/TAF (P < .0001). After adjusting for demographics, baseline ART, and CM categories, switching to BIC/FTC/TAF led to significant DDI score reductions in patients receiving CMs for cardiovascular disease, neurologic/psychiatric disorders, chronic pain, inflammation, gastrointestinal/urologic conditions, and conditions requiring hormonal therapy.ConclusionsTreatment-experienced PWH eligible to switch their ART may experience significant declines in number and severity of DDIs if switched to BIC/FTC/TAF.

Objectives: The optimal antiretroviral therapy for patients with the M184V/I mutation is not known. The primary objective of this study was to determine the efficacy of various antiretroviral therapies in patients with HIV and the M184V/I mutation based on the number of active antiretroviral agents. Methods: A retrospective chart review was conducted of 100 treatment-experienced patients harboring the M184V/I mutation seen at an urban HIV clinic. Efficacy was classified as percentage of patients with viral suppression defined as HIV RNA viral load Results: The primary outcome of viral suppression occurred in 70.6% (12/17) of patients on Conclusion: Similar rates of viral suppression were observed in patients regardless of the number of active antiretroviral agents prescribed. Regimens containing less than 3 active agents may maintain virologic suppression in patients with the M184V/I mutation. Further studies are needed to determine optimal antiretroviral therapy for patients with the M184V/I mutation.

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.

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. 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.

Persons living with human immunodeficiency virus (HIV) and others receiving antiretrovirals are at risk for medication errors during hospitalization and at transitions of care. These errors may result in adverse effects or viral resistance, limiting future treatment options. A range of interventions is described in the literature to decrease the occurrence or duration of medication errors, including review of electronic health records, clinical checklists at care transitions, and daily review of medication lists. To reduce the risk of medication-related errors, antiretroviral stewardship programs (ARVSPs) are needed to enhance patient safety. This call to action, endorsed by the Infectious Diseases Society of America, the HIV Medicine Association, and the American Academy of HIV Medicine, is modeled upon the success of antimicrobial stewardship programs now mandated by the Joint Commission. Herein, we propose definitions of ARVSPs, suggest resources for ARVSP leadership, and provide a summary of published, successful strategies for ARVSP that healthcare facilities may use to develop locally appropriate programs., Persons receiving antiretrovirals are at risk for medication-related errors in the inpatient setting. This joint policy paper endorses antiretroviral stewardship and antiretroviral stewardship programs, designed to improve patient safety

Upon completion of this chapter, the reader should be able to • Understand the basic principles of applied pharmacokinetics and pharmacodynamics of antiretroviral agents, and apply this knowledge to improve individual patient treatment regimens. Understanding the basic principles of applied clinical pharmacokinetics and pharmacodynamics can help the clinician gain insight into contemporary HIV pharmacotherapy and improve therapeutic responses. This information can be used to improve antiretroviral (ARV) treatment for the individual patient by gaining a fundamental working knowledge of concepts that contribute to the occurrence of drug–drug interactions (DDIs), adverse drug reactions, poor adherence, decreased efficacy, and the selection of viral resistance. These factors, alone or in combination, can lead to treatment failure of antiretroviral therapy (ART) and subsequent progression of HIV disease. This chapter discusses some of the applied clinical pharmacokinetic and pharmacodynamic principles that relate to the treatment of HIV....

Antimicrobial resistance is a growing global health concern. Antimicrobial stewardship (AMS) curbs resistance rates by encouraging rational antimicrobial use. However, data on antimicrobial stewardship in developing countries is scarce. The objective of this study was to characterize antimicrobial use at the University Teaching Hospital (UTH) in Lusaka, Zambia as a guiding step in the development of an AMS program. This was a cross-sectional, observational study evaluating antimicrobial appropriateness and consumption in non-critically ill adult medicine patients admitted to UTH. Appropriateness was defined as a composite measure based upon daily chart review. Sixty percent (88/146) of all adult patients admitted to the general wards had at least one antimicrobial ordered and were included in this study. The most commonly treated infectious diseases were tuberculosis, pneumonia, and septicemia. Treatment of drug sensitive tuberculosis is standardized in a four-drug combination pill of rifampicin, isoniazid, pyrazinamide and ethambutol, therefore appropriateness of therapy was not further evaluated. The most common antimicrobials ordered were cefotaxime (n = 45), ceftriaxone (n = 28), and metronidazole (n = 14). Overall, 67% of antimicrobial orders were inappropriately prescribed to some extent, largely driven by incorrect dose or frequency in patients with renal dysfunction. Antimicrobial prescribing among hospitalized patients at UTH is common and there is room for optimization of a majority of antimicrobial orders. Availability of certain antimicrobials must be taken into consideration during AMS program development.

Systemic concentrations of antiretroviral drugs (ARVs) are influenced by the pharmacokinetic properties of absorption, distribution, metabolism, and excretion. Pharmacokinetics and local drug exposure can differ significantly within anatomical sanctuary sites compared with the systemic compartment. High variability in interpatient ARV concentrations is common, which makes population pharmacokinetics for ARVs very difficult to interpret. HIV replication is dynamic and requires combination antiretroviral therapy with multiple active agents in order to achieve durable virologic suppression. Direct and indirect relationships between drug exposure, efficacy, and/or toxicity are common for most ARVs, which can be used to improve overall treatment success. Suboptimal adherence can result in inadequate concentrations, drug resistance, and virologic failure. Therapeutic drug monitoring can be considered in certain scenarios that should be evaluated on a case-by-case basis.

Pharmacologic interventions for human immunodeficiency virus (HIV) wasting have been studied since the 1990s, but the results of these interventions have been difficult to compare because the studies used different HIV wasting definitions and assessed various patient outcomes. Thus, we performed a systematic review of the current literature to identify studies that evaluated pharmacologic management of HIV wasting and to compare and contrast treatment options. Further, we provide a comprehensive review of these treatment options and describe the definition of HIV wasting used in each study, the outcomes assessed, and whether antiretroviral therapy was used during the HIV wasting treatment. Literature searches of the PubMed/Medline (1946-2014) and Google Scholar databases were performed, and a review of the bibliographies of retrieved articles was performed to identify additional references. Only English-language articles pertaining to humans and HIV-infected individuals were evaluated. Thirty-six studies were identified that assessed pharmacologic interventions to treat HIV wasting. Appetite stimulants, such as megestrol acetate, have been shown to increase total body weight (TBW) and body mass index in HIV-infected patients with wasting. Studies evaluating dronabinol showed conflicting data on TBW increases, but the drug may have minimal benefit on body composition compared with other appetite stimulants. Testosterone has been shown to be effective in HIV wasting for those who suffer from hypogonadism. Recombinant human growth hormone has been evaluated for HIV wasting and has shown promising results for TBW and lean body mass increases. Thalidomide has been studied; however, its use is limited due to its toxicities. Although megestrol acetate and dronabinol are approved by the U.S. Food and Drug Administration (FDA) for the treatment of HIV wasting, it is important to recognize other comorbidities such as depression or hypogonadism that may contribute to the patient's appetite and weight loss. If a patient is diagnosed with hypogonadism and HIV wasting, testosterone would be a good therapeutic option. Although mirtazapine is not FDA approved for the management of HIV wasting, it has been shown to promote weight gain while treating depression symptoms. Mirtazapine may be a promising pharmacologic option in the management of HIV wasting and depression, but further research is needed.

Background Although the HIV population is at an increased risk for cardiovascular disease, gaps in therapy have been described for HIV patients indicated for statin agents. This study aimed to compare statin prescribing rates between HIV-infected and uninfected patients. This is the first study comparing statin rates among these populations using the 2013 American College of Cardiology/American Heart Association lipid guidelines, which have broader inclusion criteria than previous guidelines. Methods This is a comparative, retrospective study reviewing patients eligible for a statin that had an encounter between February 1, 2017 and September 30, 2017 at two outpatient clinics within an urban, academic medical system. Patients that qualified for one of the following statin benefit groups were included: clinical atherosclerotic cardiovascular disease (ASCVD), low density lipoprotein cholesterol (LDL-C) ≥ 190 mg/dL, or diabetes with LDL-C 70–189 mg/dL between 40 and 75 years old. Patients less than 21 years old or without a lipid panel within the last 3 years were excluded. The primary outcome was the percentage of patients with HIV prescribed a statin compared with uninfected patients. Subanalyses assessed the statin gap in individual benefit groups and statin intensity distribution. Predictors associated with receiving a statin were analyzed using a logistic regression model. Results A total of 501 HIV-positive and 1625 HIV-negative patients met the study criteria. There was no statistical difference in statin prescribing rates for patients with HIV (60.7%) and those without (65.7%, OR 1.24 [0.86–1.78]). Patients with active smoking status (OR 1.28 [1.01–1.62]) or smoking history (OR 1.47 [1.17–1.84]), and older age (OR 1.05 [1.03–1.06]) were more likely to be prescribed a statin. No association was observed between prescribed statin and HIV status in each of the benefit groups. HIV patients more often received a medium intensity statin (OR 1.10 [0.52–2.32]), whereas uninfected patients more often received a high intensity statin (OR 0.43 [0.20–0.90]). Conclusion No difference in statin prescribing rates was observed in HIV vs. uninfected patients. This demonstrates the statin gap is pertinent regardless of HIV status and additional analysis is needed to investigate reasons for the gap in both populations. Disclosures All authors: No reported disclosures.

Objective To assess change in knowledge and awareness of upper respiratory-tract infections (URTIs), and appropriate antibiotic use in community-dwelling older adults. Design Single group, pre- and post-test study. Setting Two independent senior living communities in Baltimore City and Baltimore County, Maryland. Participants Older adults eligible to receive housing or other social services as defined by the study sites. Intervention Use of an interactive trivia game to educate older adults about URTIs. A 15-item pre- and postsurvey was administered to assess change in knowledge. Outcome measures Average change in pre- and postsurvey scores. Results Thirty-two seniors participated in the game intervention, with 18 completing both surveys. There was no significant difference in the total mean pre- versus postsurvey scores. Average scores of pre- and postsurveys were 9.28 and 9.17, respectively, out of 15 points (95% confidence interval 0.65 +/- 1.414; P = 0.76). Upon review of individual survey questions, two specific areas showed a significant improvement on postsurvey scores compared with baseline. Participants showed significant improvement, however, in knowledge regarding symptoms that may require the use of an antibiotic (P = 0.02) and symptomatic management of URTI symptoms (P = 0.045). Conclusions Based on survey results, we learned more about older adults' knowledge regarding URTIs, antibiotic use, and strategies to provide education to community-dwelling geriatric adults. The game was effective in teaching older adults about symptom management and symptoms that may require an antibiotic.

What is known and objective Generic manufacturers help decrease the cost of antiretroviral (ARV) and antimicrobial medications which are used to treat opportunistic infections (OIs) in developing countries. Concerns have been expressed about potential quality issues with such medications as a result of the identification of numerous counterfeit medications in developing countries. However few studies have assessed the quality of these medications using the United States Pharmacopeia (USP) compendial standards. The goal of this study was to assess the quality of ARV and OI medications obtained from various sources including South Africa United States China Ethiopia Thailand Laos Mexico Nigeria and five Internet pharmacies. Methods Zidovudine lamivudine efavirenz nevirapine isoniazid and sulfamethoxazole/trimethoprim tablets/capsules were obtained from eight countries and five Internet pharmacies. The tablets/capsules were separated into distinct samples based on the drugs active ingredient manufacturer and drug control number. Each distinct sample was analysed for drug content dissolution content uniformity and breaking force using USP 32-National Formulary 27 (USP 32-NF 27) compendial methods and compared to the USP standards. Results and discussion A total of 2027 tablets/capsules were obtained with 88 distinct samples identified. All samples met the USP 32-NF 27 standards for drug content with a range of 92·7-108·6%. Six of the 88 samples failed the dissolution test by 1·5-8·3% below the standard range. Ninety-eight per cent of all 88 samples met the USP criteria for content uniformity based on weight variation. One sample of isoniazid was found to have a low breaking force of 2·8 kiloponds. The results of this study show that there were no problems with the samples of ARV and OI medications tested for drug quality from the specified locations. As there are many studies and reports that discuss the poor quality of generic medications with only a few assessing drug quality the implications of this studys results are to: (i) help better understand patient outcomes; (ii) help patients gain access to beneficial medications for HIV and OIs; and (iii) ensure an overall increase in access to medications where needed. What is new and conclusion This study is one of the largest to date concerning medication type and sample size for the assessment of ARV and OI medications using drug content as a measure of quality. The samples were obtained from more diverse geographical locations compared to previous studies and for the first time included Internet pharmacies. In addition to drug content this study evaluated a more complete quality profile including dissolution content uniformity and breaking force. This study showed that drug quality should be assessed consistently in order to better identify counterfeit medications compared to current assessments and that there should be uniform guidelines for how to assess quality. Two thousand and twenty seven individual tablets/capsules of antiretroviral (ARV) and opportunistic infection (OI) medications were obtained from various countries and internet pharmacies. Drug quality testing was performed testing for drug identity drug content dissolution content uniformity and breaking force. The results of this study show that there were no problems with the samples of ARV and OI medications tested for drug quality.