Apples to Apples? A Comparison of Real-World Tolerability of Antiretrovirals in Patients with Human Immunodeficiency Virus Infection and Patients with Primary Biliary Cholangitis.

We previously characterized a human betaretrovirus and linked infection with the development of primary biliary cholangitis (PBC). There are in vitro and in vivo data demonstrating that antiretroviral therapy used to treat human immunodeficiency virus (HIV) can be repurposed to treat betaretroviruses. As such, PBC patients have been treated with nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), alone and in combination with a boosted protease inhibitor or an integrase strand transfer inhibitor in case studies and clinical trials. However, a randomized controlled trial using combination antiretroviral therapy with lopinavir was terminated early because 70% of PBC patients discontinued therapy because of gastrointestinal side effects. In the open-label extension, patients tolerating combination therapy underwent a significant reduction in serum liver parameters, whereas those on NRTIs alone rebounded to baseline. Herein, we compare clinical experience in the experimental use of antiretroviral agents in patients with PBC with the broader experience of using these agents in people living with HIV infection. While the incidence of gastrointestinal side effects in the PBC population appears somewhat increased compared to those with HIV infection, the clinical improvement observed in patients with PBC suggests that further studies using the newer and better tolerated antiretroviral agents are warranted.

What determines do-not-resuscitate status in critically ill HIV-infected patients admitted to ICU?

PURPOSE: To identify factors associated with do-not-resuscitate (DNR) status in critically ill patients infected with human immunodeficiency virus (HIV) admitted to the Intensive Care Unit (ICU) in the era of combination antiretroviral therapy (cART). MATERIALS AND METHODS: Retrospective cohort study of first-time admissions of HIV-infected patients to ICUs in Edmonton, Alberta, from 2002 to 2014. Multivariable logistic regression analysis was performed to identify factors associated with DNR status. RESULTS: There were 282 HIV-infected patients with first-time ICU admissions, with an incidence rate of 6.6 per 1000 ICU admissions. Sixty-seven (24%) patients had a DNR designation and support was withdrawn in 37 (13%). In multivariable analysis, APACHE II score (OR 1.13; 95% CI, 1.08-1.19, p < 0.001), coronary artery disease (OR 5.70; 95% CI, 1.18-27.76, p = 0.031), prior opportunistic infection (OR 2.59; 95% CI, 1.20-5.57, p = 0.015) and duration of HIV infection (OR 1.07 per year; 95% CI, 1.01-1.14, p = 0.025) were independently associated with DNR status. Ethnicity, HIV risk factors, CD4 count and viral load were not associated with DNR status. CONCLUSIONS: One in four patients had a DNR designation. Illness acuity, selected comorbidity, previous opportunistic infection and HIV duration were associated with DNR designation.

Mycobacterium branderi infection: Case report and literature review of an unusual and difficult-to-treat non-tuberculous mycobacterium.

A 67-year-old man with significant smoking history presented with fever, unintentional weight loss, night sweats, productive cough, and progressive dyspnea. Multiple respiratory specimens grew Mycobacterium branderi. Computed tomography scanning of the chest revealed a cavitary right upper lung lesion. Bronchoscopy and thoracoscopic biopsy were negative for malignancy but showed necrotizing granulomatous inflammation, which was culture negative. Due to clinical and radiologic progression despite therapy with clarithromycin, ethambutol and moxifloxacin, the lesion was surgically resected and the patient's symptoms resolved. Mycobacteria were seen in histopathology but did not grow from resected tissue. The patient received an additional 6 months of medical therapy and remains asymptomatic 1 month after completing antimicrobials. Cases of M. branderi causing human infection are very rarely reported. This is a novel case of multi-drug resistant M. branderi pulmonary infection in an apparently immunocompetent patient, progressive despite medical therapy and requiring surgical resection for definitive management.

Epidemiology and Outcomes in Critically Ill Patients with Human Immunodeficiency Virus Infection in the Era of Combination Antiretroviral Therapy.

Purpose. The impact of critical illness on survival of HIV-infected patients in the era of antiretroviral therapy remains uncertain. We describe the epidemiology of critical illness in this population and identify predictors of mortality. Materials and Methods. Retrospective cohort of HIV-infected patients was admitted to intensive care from 2002 to 2014. Patient sociodemographics, comorbidities, case-mix, illness severity, and 30-day mortality were captured. Multivariable Cox regression analyses were performed to identify predictors of mortality. Results. Of 282 patients, mean age was 44 years (SD 10) and 169 (59%) were male. Median (IQR) CD4 count and plasma viral load (PVL) were 125 cells/mm3 (30-300) and 28,000 copies/mL (110-270,000). Fifty-five (20%) patients died within 30 days. Factors independently associated with mortality included APACHE II score (adjusted hazard ratio [aHR] 1.12; 95% CI 1.08-1.16; p < 0.001), cirrhosis (aHR 2.30; 95% CI 1.12-4.73; p = 0.024), coronary artery disease (aHR 6.98; 95% CI 2.20-22.13; p = 0.001), and duration of HIV infection (aHR 1.07 per year; 95% CI 1.02-1.13; p = 0.01). CD4 count and PVL were not associated with mortality. Conclusions. Mortality from an episode of critical illness in HIV-infected patients remains high but appears to be driven by acute illness severity and HIV-unrelated comorbid disease rather than degree of immune suppression.

Are forested buffers an effective conservation strategy for riparian fauna? An assessment using meta-analysis.

Historically, forested riparian buffers have been created to provide protection for aquatic organisms and aquatic ecosystem functions. Increasingly, new and existing riparian buffers are being used also to meet terrestrial conservation requirements. To test the effectiveness of riparian buffers for conserving terrestrial fauna, we conducted a meta-analysis using published data from 397 comparisons of species abundance in riparian buffers and unharvested (reference) riparian sites. The response of terrestrial species to riparian buffers was not consistent between taxonomic groups; bird and arthropod abundances were significantly greater in buffers relative to unharvested areas, whereas amphibian abundance decreased. Edge-preferring species were more abundant in buffer sites than reference sites, whereas species associated with interior habitat were not significantly different in abundance. The degree of buffer effect on animal abundance was unrelated to buffer width; wider buffers did not result in greater similarity between reference and buffer sites. However, responses to buffer treatment were more variable in buffers <50 m wide, a commonly prescribed width in many management plans. Our results indicate that current buffer prescriptions do not maintain most terrestrial organisms in buffer strips at levels comparable to undisturbed sites.