Role of etravirine in the management of treatment-experienced patients with human immunodeficiency virus type 1

Etravirine is an oral diarylpyrimidine compound, a second-generation human immunodeficiency virus type 1 (HIV-1) non-nucleoside reverse transcriptase inhibitor (NNRTI) with expanded antiviral activity against NNRTI-resistant HIV-1, to be used in combination therapy for treatment-experienced patients. Compared with first-generation NNRTIs, etravirine has a high genetic barrier to resistance, and is better tolerated without the neuropsychiatric and hepatic side effects of efavirenz and nevirapine, respectively. Its safety profile is comparable to placebo with the exception of rash, which has been mild and self-limited in the great majority of patients. In phase III clinical trials among treatment-experienced patients harboring NNRTI-resistant HIV-1, etravirine in combination with an optimized background regimen (OBR) that included ritonavir-boosted darunavir demonstrated superior antiviral activity than the control OBR. In addition, patients on the etravirine arm had fewer AIDS-defining conditions, hospitalizations, and lower mortality compared with the OBR control arm

Outpatient treatment with AZD7442 (tixagevimab/cilgavimab) prevented Covid-19 hospitalizations over 6 months and reduced symptom progression in the TACKLE randomized trial

Introduction We assessed effects of AZD7442 (tixagevimab/cilgavimab) on deaths from any cause or hospitalizations due to coronavirus disease 2019 (COVID-19) and symptom severity and longer-term safety in the TACKLE adult outpatient treatment study. Methods Participants received 600 mg AZD7442 (n = 452) or placebo (n = 451) ≤ 7 days of COVID-19 symptom onset. Results Death from any cause or hospitalization for COVID-19 complications or sequelae through day 169 (key secondary endpoint) occurred in 20/399 (5.0%) participants receiving AZD7442 versus 40/407 (9.8%) receiving placebo [relative risk reduction (RRR) 49.1%; 95% confidence interval (CI) 14.5, 69.7; p = 0.009] or 50.7% (95% CI 17.5, 70.5; p = 0.006) after excluding participants unblinded before day 169 for consideration of vaccination). AZD7442 reduced progression of COVID-19 symptoms versus placebo through to day 29 (RRR 12.5%; 95% CI 0.5, 23.0) and improved most symptoms within 1–2 weeks. Over median safety follow-up of 170 days, adverse events occurred in 174 (38.5%) and 196 (43.5%) participants receiving AZD7442 or placebo, respectively. Cardiac serious adverse events occurred in two (0.4%) and three (0.7%) participants receiving AZD7442 or placebo, respectively. Conclusions AZD7442 was well tolerated and reduced hospitalization and mortality through 6 months, and symptom burden through 29 days, in outpatients with mild-to-moderate COVID-19. Clinical Trial Registration Clinicaltrials.gov, NCT04723394. (https://beta.clinicaltrials.gov/study/NCT04723394)

Outpatient Treatment with AZD7442 (Tixagevimab/Cilgavimab) Prevented COVID-19 Hospitalizations over 6 Months and Reduced Symptom Progression in the TACKLE Randomized Trial

INTRODUCTION: We assessed effects of AZD7442 (tixagevimab/cilgavimab) on deaths from any cause or hospitalizations due to coronavirus disease 2019 (COVID-19) and symptom severity and longer-term safety in the TACKLE adult outpatient treatment study. METHODS: Participants received 600 mg AZD7442 (n = 452) or placebo (n = 451) ≤ 7 days of COVID-19 symptom onset. RESULTS: Death from any cause or hospitalization for COVID-19 complications or sequelae through day 169 (key secondary endpoint) occurred in 20/399 (5.0%) participants receiving AZD7442 versus 40/407 (9.8%) receiving placebo [relative risk reduction (RRR) 49.1%; 95% confidence interval (CI) 14.5, 69.7; p = 0.009] or 50.7% (95% CI 17.5, 70.5; p = 0.006) after excluding participants unblinded before day 169 for consideration of vaccination). AZD7442 reduced progression of COVID-19 symptoms versus placebo through to day 29 (RRR 12.5%; 95% CI 0.5, 23.0) and improved most symptoms within 1-2 weeks. Over median safety follow-up of 170 days, adverse events occurred in 174 (38.5%) and 196 (43.5%) participants receiving AZD7442 or placebo, respectively. Cardiac serious adverse events occurred in two (0.4%) and three (0.7%) participants receiving AZD7442 or placebo, respectively. CONCLUSIONS: AZD7442 was well tolerated and reduced hospitalization and mortality through 6 months, and symptom burden through 29 days, in outpatients with mild-to-moderate COVID-19. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, NCT04723394. ( https://beta. CLINICALTRIALS: gov/study/NCT04723394 )

Comparison of the QuantiFERON TB Gold In-tube Assay With Tuberculin Skin Test for the Diagnosis of Latent Tuberculosis Infection Among HIV-infected and Uninfected Children.

BACKGROUND: Diagnosis of latent tuberculosis infection (LTBI) is facilitated by tuberculin skin testing (TST) or interferon-gamma release assays such as the QuantiFERON TB Gold In-Tube (QTF-GIT) assays. Limited data exist on the utility of interferon-gamma release assays in HIV-infected children, which may be falsely negative due to immunosuppression. METHODS: A cross-sectional study comparing TST to QTF-GIT for the diagnosis of suspected LTBI was performed in children in Tijuana, Mexico, and in San Diego, California. Concordance between TST (≥5 mm for HIV infected and ≥10 mm for HIV uninfected) and QTF-GIT was evaluated utilizing kappa coefficients. Multivariate logistic regression assessed factors influencing the results. RESULTS: One hundred sixty-five children (70 HIV infected and 95 HIV uninfected) were evaluated (median age, 8.0 years). Among HIV-infected children, the median CD4 cell count was 913 cells/μL, with 92.9% of subjects on antiretroviral treatment and 80.0% with an HIV RNA load/mL (76%/mL). Among HIV-infected children with no history of tuberculosis, 12 HIV had either a positive QTF-GIT or TST ≥ 5 mm or both, giving a suspected LTBI prevalence of 20.3% (compared with 61.3% among HIV-uninfected children). Moderate concordance was demonstrated in HIV-infected children (both tests positive, κ = 0.42; 95% confidence interval: 8.9%-75.4%) and HIV-uninfected children (both tests positive, κ = 0.59; 95% confidence interval: 43.0%-76.5%). CONCLUSIONS: A moderate correlation exists between TST and QTF-GIT among HIV-infected and uninfected children with preserved immune function in an area of moderate tuberculosis endemicity