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Abstract: Crushed oral tablets, when injected intravenously, may induce a foreign body granulomatous reaction in and around pulmonary arterioles, because of the presence of filler materials (excipients). This typically presents as shortness of breath in the context of pulmonary hypertension with arteriolar dilation and centrilobular nodules on imaging modalities. The constellation of findings may be overlooked or misdiagnosed by clinicians and pathologists, ultimately affecting patient care and postmortem assessment. We describe 5 patients with excipient lung disease that had antemortem chronic medical conditions that required a peripherally inserted catheter or port. All 5 patients had intravascular and perivascular deposition of polarizable foreign material within the pulmonary arteries. Foreign body granulomatosis as a result of intravenous drug use was not clinically suspected in any patient, and 2 of the 5 patients were misdiagnosed with mycobacterium infections. Pulmonary congestion, dyspnea, and symptoms of heart failure were noted in 3 patients and 2 had a history of upper arm deep vein thrombosis. We conclude that excipient lung disease may be underdiagnosed cause of dyspnea, pulmonary hypertension, and death in patients with a known history of intravenous drug use., Competing Interests: The authors report no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Antiretroviral drugs contained in single tablet Atripla have pharmacokinetic properties that could allow for longer than once-daily dosing. We hypothesized that simplifying Atripla once daily to 3-day per week would be feasible, able to maintain viral suppression and less toxic., Methods: Virologically suppressed (≥2 years) HIV+ adults on Atripla once daily, CD4 greater than 350 cells/μl at inclusion, and no prior documented virological failure or evidence of resistance mutations to efavirenz, tenofovir, or emtricitabine were randomized to maintain their once-daily (OD) regimen or to reduce it to 3 days (Mondays, Wednesdays, and Fridays) a week (3W) (A-TRI-WEEK pilot trial). Primary end-point was the proportion of patients free of treatment failure (noncompleter = failure) at 24 weeks. CD4 and CD8 cells, ultrasensitive HIV-1 RNA, Pittsburg Sleep Quality Index (PSQI), bone mineral density, plasma efavirenz levels, and fasting blood and urine chemistries were measured at baseline and 24 weeks. The study is registered at ClinicalTrials.gov, NCT01778413., Results: Sixty-one patients were randomized. All patients in both arms remained free of treatment failure (estimated difference 0%; 95% confidence interval -14.1 to 14.1). Ultrasensitive plasma HIV-1 RNA below detection threshold showed no difference between arms (70% in the 3W arm vs. 71% in the OD arm, P = 0.933) at 24 weeks. Total cholesterol and femur T-score significantly increased, whereas PSQI, plasma efavirenz, albumin/creatinine and beta-2-microglobulin in urine significantly decreased in the 3W arm relative to OD arm., Conclusion: The A-TRI-WEEK study represents a proof of concept for the feasibility of three-day per week Atripla maintenance that should be further confirmed in a larger, well powered clinical trial.

Objectives: To compare efficacy, safety, tolerability, and patient-reported outcomes between two single-tablet regimens, rilpivirine/emtricitabine/tenofovir disoproxil fumarate (RPV/FTC/TDF) and efavirenz/emtricitabine/tenofovir disoproxil fumarate (EFV/FTC/TDF), in HIV-1-infected, treatment-naive adults., Design: This was a phase 3b, 96-week, randomized, open-label, international, noninferiority trial., Methods: A total of 799 participants were randomized (1 : 1) to receive RPV/FTC/TDF or EFV/FTC/TDF. The primary efficacy endpoint evaluated proportions of participants with HIV-1 RNA less than 50 copies/ml using the Snapshot algorithm. Additional assessments included CD4 cell counts, genotypic/phenotypic resistance, adverse events, patient-reported outcomes, and quality of life questionnaires., Results: At week 96, trial completion rates were 80.2% (316/394; RPV/FTC/TDF) and 74.0% (290/392; EFV/FTC/TDF). Overall, RPV/FTC/TDF was noninferior to EFV/FTC/TDF [HIV-1 RNA <50 copies/ml: 77.9 vs. 72.4%, respectively; difference -5.5; 95%CI (-0.6, 11.5); P = 0.076]. RPV/FTC/TDF was significantly more efficacious compared with EFV/FTC/TDF in participants with baseline HIV-1 RNA equal to or less than 100 000 copies/ml (78.8 vs. 71.2%; P = 0.046) and in those with CD4 cell count greater than 200 cells/μl (80.6 vs. 73.0%; P = 0.018). There was no significant between-group difference in the CD4 cell count increase (278 ± 189 vs. 259 ± 191 cells/μl; P = 0.17). Few participants developed resistance after week 48 (1.0% RPV/FTC/TDF; 0.3% EFV/FTC/TDF). Compared with EFV/FTC/TDF, RPV/FTC/TDF was associated with fewer adverse event-related discontinuations (3.0 vs. 11.0%; P<0.001), significantly fewer adverse events due to central nervous system issues and rash, greater improvements in patient-reported symptoms, and significant improvements in the SF-12v2 quality of life questionnaire mental health composite score (P = 0.014)., Conclusion: In treatment-naive, HIV-1-infected participants, 96-week RPV/FTC/TDF treatment demonstrated noninferior efficacy and better tolerability than EFV/FTC/TDF.

Purpose of Review: The most common cause of esophageal injury is gastroesophageal reflux disease, however other less recognized causes may affect the esophagus. In this review we will focus on pill-induced esophageal injury, infections of the esophagus and eosinophilic esophagitis., Recent Findings: Esophageal infections are less frequent since HIV infection has become better controlled with antiviral therapies. The most emergent 'allergic' disease of the esophagus is eosinophilic esophagitis, which has become increasingly recognized in children and adults over the last decade. Eosinophilic esophagitis is a clinicopathologic disorder characterized by a dense esophageal eosinophilia generally occurring in association with upper gastrointestinal symptoms, primarily intermittent dysphagia, and refractory to proton pump inhibitor therapy., Summary: Drug-induced esophageal injury remains underdiagnosed and should be better recognized.