Introduction HIV‐1 infection leads to chronic inflammation and to an increased risk of non‐AIDS mortality. Our objective was to determine whether AIDS‐defining events (ADEs) were associated with increased overall and cause‐specific non‐AIDS related mortality after antiretroviral therapy (ART) initiation.MethodsWe included HIV treatment‐naïve adults from the Antiretroviral Therapy Cohort Collaboration (ART‐CC) who initiated ART from 1996 to 2014. Causes of death were assigned using the Coding Causes of Death in HIV (CoDe) protocol. The adjusted hazard ratio (aHR) for overall and cause‐specific non‐AIDS mortality among those with an ADE (all ADEs, tuberculosis (TB), Pneumocystis jiroveci pneumonia (PJP), and non‐Hodgkin's lymphoma (NHL)) compared to those without an ADE was estimated using a marginal structural model.ResultsThe adjusted hazard of overall non‐AIDS mortality was higher among those with any ADE compared to those without any ADE (aHR 2.21, 95% confidence interval (CI) 2.00 to 2.43). The adjusted hazard of each of the cause‐specific non‐AIDS related deaths were higher among those with any ADE compared to those without, except metabolic deaths (malignancy aHR 2.59 (95% CI 2.13 to 3.14), accident/suicide/overdose aHR 1.37 (95% CI 1.05 to 1.79), cardiovascular aHR 1.95 (95% CI 1.54 to 2.48), infection aHR (95% CI 1.68 to 2.81), hepatic aHR 2.09 (95% CI 1.61 to 2.72), respiratory aHR 4.28 (95% CI 2.67 to 6.88), renal aHR 5.81 (95% CI 2.69 to 12.56) and central nervous aHR 1.53 (95% CI 1.18 to 5.44)). The risk of overall and cause‐specific non‐AIDS mortality differed depending on the specific ADE of interest (TB, PJP, NHL).ConclusionsIn this large multi‐centre cohort collaboration with standardized assignment of causes of death, non‐AIDS mortality was twice as high among patients with an ADE compared to without an ADE. However, non‐AIDS related mortality after an ADE depended on the ADE of interest. Although there may be unmeasured confounders, these findings suggest that a common pathway may be independently driving both ADEs and NADE mortality. While prevention of ADEs may reduce subsequent death due to NADEs following ART initiation, modification of risk factors for NADE mortality remains important after ADE survival.

Persistent neutrophilic meningitis presents a diagnostic challenge, because the differential diagnosis is broad and includes atypical infectious causes. We describe a case of persistent neutrophilic meningitis due to Aspergillus fumigatus in an immunocompetent man who had no evidence of sinopulmonary or cutaneous disease. An epidural glucocorticoid injection was identified as a potential route of entry for this organism into the central nervous system, and the case was reported to the state health department.

NCT01622140.

We report 3 cases of herpes simplex virus encephalitis in patients receiving tumor necrosis factor-alpha (TNF-α) inhibitors for rheumatologic disorders. Although TNF-α inhibitors have been reported to increase the risk of other infectious diseases, to our knowledge, an association between anti–TNF-α drugs and herpes simplex virus encephalitis has not been previously described.

Introduction/Objectives: Pre-exposure prophylaxis (PrEP) use in the southern United States is low despite its effectiveness in preventing HIV acquisition and high regional HIV prevalence. Our objectives were to assess PrEP knowledge, attitudes, and prescribing practices among Tennessee primary care providers. Methods: We developed an anonymous cross-sectional electronic survey from March to November 2019. Survey development was guided by the Capability, Opportunity, Motivation, and Behavior framework and refined through piloting and interviews. Participants included members of professional society and health center listservs licensed to practice in Tennessee. Respondents were excluded if they did not complete the question regarding PrEP prescription in the previous year or were not in a position to prescribe PrEP (e.g., hospital medicine). Metrics included PrEP prescription in the preceding year, PrEP knowledge scores (range 0-8), provider attitudes about PrEP, and provider and practice characteristics. Knowledge scores and categorical variables were compared across PrEP prescriber status with Wilcoxon rank-sum and Fisher’s exact tests, respectively. Results: Of 147 survey responses, 99 were included and 43 (43%) reported PrEP prescription in the preceding year. Compared with non-prescribers: prescribers had higher median PrEP knowledge scores (7.3 vs 5.6, P < .01), a higher proportion had self-reported patient PrEP inquiries (95% vs 21%, P < .01), and a higher proportion had self-reported good or excellent ability to take a sexual history (83% vs 58%, P = .01) and comfort taking a sexual history (92% vs 63%, P < .01) from men who have sex with men, a subgroup with high HIV risk. Most respondents felt obligated to provide PrEP (65%), and felt all primary care providers should provide PrEP (63%). Conclusion: PrEP provision is significantly associated with PrEP knowledge, patient PrEP inquiries, and provider sexual history taking ability and comfort. Future research should evaluate temporal relationships between these associations and PrEP prescription as potential routes to increase PrEP provision.

SETTING Programmatic data from the United States on tuberculosis (TB) recurrence are limited. OBJECTIVES To determine the TB recurrence rate and to determine if chronic lung disease (CLD) and human immunodeficiency virus (HIV) infection are risk factors for recurrence in this population. DESIGN Nested case-control study among TB cases reported to the Tennessee Department of Health between 1 January 2000 and 31 December 2006. Time at risk for recurrence was through 31 December 2007. Multiple imputation accounted for missing data. RESULTS Of 1431 TB cases, 20 cases recurred (1.4%, 95%CI 0.9–2.1). Median time at risk for recurrence was 4.5 years (interquartile range 2.7–6.1). Initial and recurrent Mycobacterium tuberculosis isolates were available for genotyping for 15 patients; 12 were consistent with relapse (0.8%, 95%CI 0.4–1.5) and three with re-infection (0.2%, 95%CI 0.04–0.6). HIV infection (OR 5.01, P = 0.04) and CLD (OR 5.28, P = 0.03) were independently associated with recurrent TB, after adjusting for a disease risk score. HIV infection was a risk factor for TB re-infection (P < 0.001). CONCLUSIONS In this low-incidence US population, the TB recurrence rate was low, but CLD and HIV were independent risk factors for recurrence. HIV infection was also a risk factor for TB re-infection.

SUMMARY Objectives To determine the rate of and risk factors for discontinuation of isoniazid due to adverse effects during the treatment of latent tuberculosis infection in a large, multi-site study. Methods The Tuberculosis Epidemiologic Studies Consortium (TBESC) conducted a prospective study from March 2007–September 2008 among adults initiating isoniazid for treatment of LTBI at 12 sites in the US and Canada. The relative risk for isoniazid discontinuation due to adverse effects was determined using negative binomial regression. Adjusted models were constructed using forward stepwise regression. Results Of 1,306 persons initiating isoniazid, 617 (47.2%, 95% CI 44.5–50.0%) completed treatment and 196 (15.0%, 95% CI 13.1–17.1%) discontinued due to adverse effects. In multivariable analysis, female sex (RR 1.67, 95% CI 1.32–2.10, p<0.001) and current alcohol use (RR 1.41, 95% CI 1.13–1.77, p=0.003) were independently associated with isoniazid discontinuation due to adverse effects. Conclusions The rate of discontinuation of isoniazid due to adverse effects was substantially higher than reported earlier. Women were at increased risk of discontinuing isoniazid due to adverse effects; close monitoring of women for adverse effects may be warranted. Current alcohol use was also associated with isoniazid discontinuation; counseling patients to abstain from alcohol could decrease discontinuation due to adverse effects.

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