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Background: Influenza, respiratory syncytial virus (RSV), and human metapneumovirus (hMPV) are common respiratory viruses causing similar symptoms. Optimal tools to assess illness severity for these viruses have not been defined. Using the Hospitalized Acute Respiratory Tract Infection (HARTI) study data, we report symptom severity by clinician‐rated clinical severity scores (CSS) in adults with influenza, RSV, or hMPV and correlations between CSS and patient‐reported outcomes (PROs). Methods: HARTI was a global epidemiologic study in adults hospitalized with acute respiratory tract infections. Patients were assessed at enrollment within 24 h of admission with CSS and twice during hospitalization with CSS, Respiratory Infection Intensity and Impact Questionnaire™ (RiiQ™), and EQ‐5D‐5L. Data were summarized descriptively, stratified by pathogen and baseline and hospitalization characteristics. Domain (general, upper respiratory, and lower respiratory) and sign/symptom subscores are presented for CSS; sign/symptom subscores are presented for RiiQ™ results. Results: Data from 635 patients with influenza, 248 with RSV, and 107 with hMPV were included. At enrollment, total CSS and general and lower respiratory signs/symptoms (LRS) scores were higher for RSV and hMPV than influenza. Between‐pathogen differences were greatest for LRS scores. Dyspnea, rales/rhonchi, wheezing, and shortness of breath scores trended higher for RSV and hMPV than influenza. RiiQ™ scores for cough, fatigue, and short of breath were strongly correlated with corresponding clinician‐rated symptoms. Conclusions: These findings support the use of PROs (e.g., the RiiQ™) correlating with clinician assessments to gauge patient well‐being and aid patient management by accurately assessing respiratory illness severity due to RSV, hMPV, or influenza. [ABSTRACT FROM AUTHOR]

In treatment-naive adults infected with human immunodeficiency virus type 1, once-daily rilpivirine with a background regimen was associated with fewer lipid changes and comparable body fat changes than efavirenz during 96 weeks of treatment. The background nucleoside/nucleotide reverse transcriptase inhibitor regimen affected lipid levels and body fat distribution changes.Background. Pooled ECHO/THRIVE lipid and body fat data are presented from the ECHO (Efficacy Comparison in Treatment-Naïve, HIV-Infected Subjects of TMC278 and Efavirenz) and THRIVE (TMC278 Against HIV, in a Once-Daily Regimen Versus Efavirenz) trials.Methods. We assessed the 96-week effects on lipids, adverse events (AEs), and body fat distribution (dual-energy x-ray absorptiometry) of rilpivirine (RPV) and EFV plus 2 nucleoside/nucleotide reverse transcriptase inhibitors (N[t]RTIs) in treatment-naive adults infected with human immunodeficiency virus type 1 (HIV-1).Results. Rilpivirine produced minimal changes in total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides. Compared with RPV, EFV significantly (P < .001) increased lipid levels. Decreases in the TC/HDL-C ratio were similar with RPV and EFV. Background N[t]RTI affected RPV-induced lipid changes; all levels increased with zidovudine/lamivudine (3TC) and abacavir/3TC (except triglycerides, which were unchanged). With emtricitabine/tenofovir, levels of HDL-C were increased, TC and LDL-C were unchanged, and triglycerides were decreased. With EFV, lipid levels increased in each N[t]RTI subgroup (except triglycerides were unchanged with abacavir/3TC). Fewer (P < .001) RPV-treated patients than EFV-treated patients had TC, LDL-C, and triglyceride levels above National Cholesterol Education Program cutoffs. More RPV- than EFV-treated patients had HDL-C values below these cutoffs (P = .02). Dyslipidemia AEs were less common with RPV than with EFV. Similar proportions of patients had a ≥10% decrease in limb fat (16% with RPV and 17% with EFV). Limb fat was significantly (P < .001) increased to a similar extent (by 12% with RPV and 11% with EFV). At week 96, patients receiving zidovudine/3TC had lost limb fat, and those receiving emtricitabine/tenofovir had gained it.Conclusions. Over the course of 96 weeks, RPV-based therapy was associated with lower increases in lipid parameters and fewer dyslipidemia AEs than EFV-based treatment. Body fat distribution changes were similar between treatments. The N[t]RTI regimen affected lipid and body fat distribution changes. [ABSTRACT FROM PUBLISHER]

Objective: Pharmacokinetics, safety, and tolerability of GSK1265744 (744) and rilpivirine (RPV) (TMC278) were assessed after repeat dosing of long-acting (LA) injectable formulations in healthy subjects., Methods: Subjects received a 14-day lead-in of oral 744 (30 mg/d) to assess safety and tolerability before injectable administration. Subjects were randomized into 4 cohorts: 800 mg of 744 LA intramuscularly (IM) followed by 3 monthly doses of (1) 200 mg subcutaneously, (2) 200 mg IM, (3) 400 mg IM, or (4) a second injection of 800 mg IM after 12 weeks. Cohorts 2 and 3 also received IM doses of RPV LA at months 3 (1200 mg) and 4 (900 or 600 mg). Pharmacokinetics and safety were assessed throughout the trial., Results: Forty-seven subjects enrolled; 40 received ≥1 LA injection with 37 completing all planned injections. Seven subjects discontinued 744 oral (non-drug-related, n = 6; dizziness, n = 1). The 744 LA and RPV LA injections were generally well tolerated, with grade 1 injection site reactions most commonly reported. Three subjects discontinued during injection phase (consent withdrawn, n = 2; self-limited rash, n = 1). There were no grade 3 or 4 adverse events and no clinically significant trends in laboratory abnormalities, electrocardiograms, or vital signs. All dose cohorts achieved therapeutically relevant plasma concentrations of each drug within 3 days with prolonged exposure over the dosing interval. Plasma concentrations of 744 exceeded the protein-adjusted IC90 and RPV plasma concentrations and were comparable to steady-state oral RPV 25 mg/d., Conclusions: These data support the potential application of dual-therapy 744 LA and RPV LA for treatment of HIV-1 infection.

Rilpivirine (TMC278) is a non-nucleoside reverse transcriptase inhibitor approved in combination with other antiretrovirals for the treatment of HIV-1 infection in treatment-naive adults (Edurant(®) 25 mg once daily; Complera(®) [USA]/Eviplera(®) [EU] once daily single-tablet regimen). Rilpivirine should be administered with a meal to optimize bioavailability. Its solubility is pH dependent. Rilpivirine is primarily excreted via the feces with negligible renal elimination. Rilpivirine is predominantly metabolized by cytochrome P450 3A4. There is no clinically relevant effect of age, gender, bodyweight, race, estimated glomerular filtration rate, or hepatitis B/C coinfection status on rilpivirine pharmacokinetics in adults. Drug-drug interactions were investigated with cytochrome P450 3A substrates, inducers and inhibitors, drugs altering intragastric pH, antiretrovirals, and other often coadministered drugs. Rilpivirine 25 mg once daily does not have a clinically relevant effect on exposure of coadministered drugs. Coadministration with cytochrome P450 3A inhibitors (ketoconazole, ritonavir-boosted protease inhibitors, telaprevir) results in increased rilpivirine plasma concentrations, but these are not considered clinically relevant; no dose adjustments are required. Coadministration of rilpivirine with cytochrome P450 3A inducers (e.g. rifampin, rifabutin) or compounds increasing gastric pH (e.g. omeprazole, famotidine) results in decreased rilpivirine plasma concentrations, which may increase the risk of virologic failure and resistance development. Therefore, strong cytochrome P450 3A inducers and proton-pump inhibitors are contraindicated. Histamine-2 receptor antagonists and antacids can be coadministered with rilpivirine, provided doses are temporally separated. No dose adjustments are required when rilpivirine is coadministered with: acetaminophen, phosphodiesterase type 5 inhibitors (sildenafil, etc.), atorvastatin (and other statins), oral contraceptives (ethinyl estradiol, norethindrone), chlorzoxazone (cytochrome P450 2E1 substrate), methadone, digoxin, tenofovir disoproxil fumarate, didanosine and other nuceos(t)ide reverse transcriptase inhibitors, and HIV integrase inhibitors (raltegravir, dolutegravir, GSK1265744).