Angiolipoma associated with antiretroviral switch therapy: a case report.

BACKGROUND: Angiolipomas have been well described in patients with HIV exposed to protease inhibitors with possible resolution after switching to non-nucleoside reverse transcriptase inhibitor-based regimens. Resolution of symptoms have occurred with switches to non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens; however, little is known regarding the development of angiolipomas when switching from NNRTI- to modern, integrase strand transfer inhibitor-based regimens. We describe a patient who underwent switch therapy from tenofovir disoproxil fumarate/emtricitabine/efavirenz (TDF/FTC/EFV) to tenofovir alafenamide/FTC/bictegravir (TAF/FTC/BIC) who later developed angiolipomas. CASE PRESENTATION: A 55-year-old male had been on TDF/FTC/EFV for 8 years before switching to TAF/FTC/BIC. Nineteen months after antiretroviral switch, the patient presented with multiple lesions in the upper extremities and abdomen. Diagnostic biopsies revealed non-encapsulated angiolipomas and HHV-8 and non-alcoholic fatty liver disease was ruled out. New lesions continued to appear 29 months after ART switch, after which now lesions appeared and prior lesions remained stable with no increase in size noted. No surgical intervention or change in antiretroviral therapy was needed. CONCLUSIONS: Angiogenesis may have been suppressed with TDF/FTC/EFV treatment, however when switched to TAF/FTC/BIC, promoted the growth of angiolipomas. Clinicians should be aware of the impact of switching to modern ART therapies resulting in possible adipogenesis.

Statin gap in patients living with HIV: assessing dose appropriateness.

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 < 0.001). Similar rates of statin omission were seen in both populations (P = 0.11). More PLWH received too low a dose compared with the uninfected population (P < 0.0064). There were lower ASD rates in PLWH for subgroups of patients with clinical ASCVD (P = 0.00013) and 10-year ASCVD risk ≥7.5% (P = 0.00055), but not in patients with low-density lipoprotein cholesterol ≥190 mg/dL or diabetes. CONCLUSIONS: Although a statin gap exists in both PLWH and uninfected patients, the clinical significance may be greater for PLWH given the increased risk of ASCVD. This study confirms a larger statin gap in PLWH, particularly when underdosing of statin medications is considered. Additional analysis is warranted to investigate reasons for the ASD gap and beneficial clinical interventions.

Virologic suppression in patients with a documented M184V/I mutation based on the number of active agents in the antiretroviral regimen.

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 <200 copies/mL at last measurement on current antiretroviral therapy, stratified by the number of active antiretroviral agents. RESULTS: The primary outcome of viral suppression occurred in 70.6% (12/17) of patients on <2 active agents, 77.2% (44/57) on 2-2.5 active agents, and 69.2% (18/26) on 3 active agents. No significant difference was found between viral suppression and patients on <2 and 2-2.5 antiretroviral agents (odds ratio = 0.71, 95% confidence interval = (0.21, 2.39), p = 0.8) or between patients on 3 and 2-2.5 active agents (odds ratio = 0.66, 95% confidence interval = (0.23, 1.88), p = 0.7). The most commonly prescribed regimen consisted of a boosted protease inhibitor with an integrase strand transfer inhibitor and two nucleoside reverse transcriptase inhibitors, one of which being lamivudine or emtricitabine. 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.

A Call to Action: The Role of Antiretroviral Stewardship in Inpatient Practice, a Joint Policy Paper of the Infectious Diseases Society of America, HIV Medicine Association, and American Academy of HIV Medicine.

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.

The effect of veno-arterial extracorporeal oxygenation and nasogastric tube administration on the pharmacokinetic profile of abacavir, lamivudine and dolutegravir: a case report.

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.

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.

Quality of antiretroviral and opportunistic infection medications dispensed from developing countries and Internet pharmacies.

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 drug's 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 study's 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.

Use of an interactive trivia game to increase knowledge and awareness of appropriate antibiotic use in community-dwelling older adults: a pilot survey.

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.

Pharmacologic management of human immunodeficiency virus wasting syndrome.

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.