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BACKGROUND Severe coronavirus disease 2019 (Covid-19) is associated with dysregulated inflammation. The effects of combination treatment with baricitinib, a Janus kinase inhibitor, plus remdesivir are not known. METHODS We conducted a double-blind, randomized, placebo-controlled trial evaluating baricitinib plus remdesivir in hospitalized adults with Covid-19. All the patients The primary outcome was the time to recovery. The key secondary outcome was clinical status at day 15. RESULTS A total of 1033 patients underwent randomization (with 515 assigned to combination treatment and 518 to control). Patients receiving baricitinib had a median time to recovery of 7 days (95% confidence interval [CI], 6 to 8), as compared with 8 days (95% CI, 7 to 9) with control (rate ratio for recovery, 1.16; 95% CI, 1.01 to 1.32; P=0.03), and a 30% higher odds of improvement in clinical status at day 15 (odds ratio, 1.3; 95% CI, 1.0 to 1.6). Patients receiving high-flow oxygen or noninvasive ventilation at enrollment had a time to recovery of 10 days with combination treatment and 18 days with control (rate ratio for recovery, 1.51; 95% CI, 1.10 to 2.08). The 28-day mortality was 5.1% in the combination group and 7.8% in the control group (hazard ratio for death, 0.65; 95% CI, 0.39 to 1.09). Serious adverse events were less frequent in the combination group than in the control group (16.0°/0 vs. 21.0%; difference, -5.0 percentage points; 95% CI, -9.8 to -0.3; P=0.03), as were new infections (5.9% vs. 11.296; difference, -5.3 percentage points; 95% CI, -8.7 to -1.9; P=0.003). CONCLUSIONS Baricitinib plus remdesivir was superior to remdesivir alone in reducing recovery time and accelerating improvement in clinical status among patients with Covid-19, notably among those receiving high-flow oxygen or noninvasive ventilation. The combination was associated with fewer serious adverse events. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT04401579.) [ABSTRACT FROM AUTHOR]

Objective: To identify individual-level early warning indicators of virologic failure in HIV patients receiving antiretroviral therapy (ART) in South Africa., Design: A matched case-control study of individuals with and without virologic failure (VF) (>5 months on ART and HIV-1 plasma viral load >1,000 copies/mL) was conducted between June 2014 and June 2018. Of the 1,000 participants enrolled in the parent cohort, 96 experienced VF, and 199 additional controls were identified from the parent cohort and matched 1:2 (some matched 1:3) for sex, age, ART duration, and site. Participants were interviewed while clinical, pharmacy refill, laboratory, and objective pharmacological data were obtained. Multivariate conditional logistic regression models were constructed using model selection to identify factors associated with VF. Significant determinants of VF were identified using an alpha level of 0.05., Results: In a full conditional model, higher cumulative ART adherence, quantified using tenofovir-diphosphate concentrations in dried blood spots (OR 0.26) and medication possession ratio (OR 0.98) were protective against VF, whereas an increase in total depression score (OR 1.20) was predictive of VF., Conclusion: This analysis demonstrates the importance of depression as a key individual-level early warning indicator of VF. Efforts to address mental health concerns among patients with people living with HIV could improve virologic suppression., Competing Interests: Conflict of interest: The author VCM has received investigator-initiated research grants (to the institution) and consultation fees (both unrelated to the current work) from Eli Lilly (Indianapolis, IN, USA), Bayer (Leverkusen, Germany), Gilead Sciences (Foster City, CA, USA), and ViiV (Brentford, UK). DRK has received consulting honoraria AbbVie, Gilead, GlaxoSmithKline (Brentford, UK), Janssen (Beerse, Belgium), Merck (Rahway, NJ, USA) Roche (Basel, Switzerland), and ViiV; research support from Gilead, Merck, and ViiV; and speaking fees from Gilead and Janssen., (© 2024 The Authors.)

Culture-based diagnostics are the gold standard for diagnosing pulmonary TB (PTB). We characterized culture practices by comparing cases with documented sputum culture to those without.Using multivariable logistic regression, we examined associations between PTB case characteristics and no documented sputum culture reported to the U.S. National TB Surveillance System during 2011-2021.Among 69,538 PTB cases analyzed, no sputum culture attempt was documented for 5,869 (8%). Non-sputum culture specimens were documented for 54%, 80%, and 89% of cases without documented sputum culture attempts among persons aged <15 years, 15-64, and 65+ years, respectively; bronchial fluid and lung tissue were common non-sputum specimens among cases in persons >15 years old. Having no documented sputum culture was associated with age <15 years (aOR 23.84, 99% CI 20.09-28.27) or ≥65 years (aOR 1.22, 99% CI 1.07-1.39), culture of a non-sputum specimen (aOR 6.57, 99% CI 5.93-7.28), residence in a long-term care facility (aOR 1.58, 99% CI 1.23-2.01), and receiving TB care outside of a health department (aOR 1.79, 99% CI 1.61-1.98).Inability to obtain sputum from children and higher diagnostic suspicion for disease processes that require tissue-based diagnostics could explain these findings..

Background: People with HIV (PWH) are at a disproportionate risk for experiencing both chronic pain and opioid use disorder (OUD). Prescription opioid tapering is typically addressed within the "silo model" of medical care, whereby attention is focused solely on opioid addiction rather than also addressing chronic pain management, and limited communication occurs between patient and providers., Objective: This descriptive case study examined an integrative, collaborative care model consisting of Provider, Physical Therapist (PT), and Patient aimed at decreasing chronic pain and opioid use within a multidisciplinary HIV/AIDS clinic., Method: A physical-therapy based model of chronic pain mitigation and physician-driven opioid tapering was implemented. The Provider, PT, and Patient worked collaboratively to address physiological pain, pain coping skills and opioid tapering. A patient case example was used to illustrate the implementation of the model for a future, larger study in the same patient population., Results: This model was feasible in this case example in terms of clinic workflow and acceptability to both the Patient and Providers in this clinic. After the intervention, the Patient's pain was fully eliminated, and he had ceased all opioid use., Conclusion: Results of this case study suggest that utilizing an integrative, patient-centered approach to both chronic pain management and opioid tapering may be feasible within the context of a multidisciplinary HIV/AIDS clinic. Generalizability is limited by case study model; however, this gives insight into the value of a collaborative alternative compared to a "silo" model of opioid tapering and chronic pain management in preparation for a larger study., Competing Interests: Disclosure Statement No potential conflict of interest was reported by the authors.

Objectives: The contribution of depression to mortality in adults with and without HIV infection is unclear. We hypothesized that depression increases mortality risk and that this association is stronger among those with HIV infection., Methods: Veterans Aging Cohort Study (VACS) data were analysed from the first clinic visit on or after 1 April 2003 (baseline) to 30 September 2015. Depression definitions were: (1) major depressive disorder defined using International Classification of Diseases, Ninth Revision (ICD-9) codes; (2) depressive symptoms defined as Patient Health Questionnaire (PHQ)-9 scores ≥ 10. The outcome was all-cause mortality. Covariates were demographics, comorbid conditions and health behaviours., Results: Among 129 140 eligible participants, 30% had HIV infection, 16% had a major depressive disorder diagnosis, and 24% died over a median follow-up time of 11 years. The death rate was 25.3 [95% confidence interval (CI) 25.0-25.6] deaths per 1000 person-years. Major depressive disorder was associated with mortality [hazard ratio (HR) 1.04; 95% CI 1.01, 1.07]. This association was modified by HIV status (interaction P-value = 0.02). In HIV-stratified analyses, depression was significantly associated with mortality among HIV-uninfected veterans but not among those with HIV infection. Among those with PHQ-9 data (n = 7372), 50% had HIV infection, 22% had PHQ-9 scores ≥ 10, and 28% died over a median follow-up time of 12 years. The death rate was 27.3 (95% CI 26.1-28.5) per 1000 person-years. Depressive symptoms were associated with mortality (HR 1.16; 95% CI 1.04, 1.28). This association was modified by HIV status (interaction P-value = 0.05). In HIV-stratified analyses, depressive symptoms were significantly associated with mortality among veterans with HIV infection but not among those without HIV infection., Conclusions: Depression was associated with all-cause mortality. This association was modified by HIV status and method of depression ascertainment., (© 2019 British HIV Association.)

Objective: To move closer to achieving the third target of the UNAIDS 90-90-90 goals, we prospectively implemented a viral load (VL) champion (VLC) program aimed at enhancing VL monitoring and recognition of treatment failure. Design: Three clinics in eThekwini, Kwa-Zulu Natal (low-, medium- and high-volume, encompassing 9184 patients overall) were each assigned a VLC. We employed a descriptive analysis (chart audit) to compare the pre-intervention period to a 1-year post-intervention period. The number of patients with a VL test performed 6 and 12 months after the intervention was calculated as a proportion of VL tests due at those time points (VL completion rate). Results: The pre-implementation VL completion rate at the three sites was respectively 68% (140/205 patients), 54% (84/155 patients) and 64% (323/504 patients), and the 6-month post-implementation completion rate increased to 83% (995/1194 patients), 90% (793/878 patients) and 99% (3101/3124 patients) ( P < 0.0001 for each site). VL completion rates remained significantly higher at 12 months post-implementation, with an average cumulative VL completion rate of >90% across all facilities. Conclusion: We demonstrate a successful, multifaceted, quality-improvement intervention centered on a clinic-level VLC which, taken to scale, has important implications for attaining the third UNAIDS 90-90-90 target., Competing Interests: Conflicts of interest: none declared.