Putative invasive pulmonary aspergillosis in critically ill patients with COVID-19: An observational study from New York City.

BACKGROUND: Critically ill patients with coronavirus disease-2019 (COVID-19) are at the theoretical risk of invasive pulmonary aspergillosis (IPA) due to known risk factors. PATIENTS/METHODS: We aimed to describe the clinical features of COVID-19-associated pulmonary aspergillosis at a single centre in New York City. We performed a retrospective chart review of all patients with COVID-19 with Aspergillus isolated from respiratory cultures. RESULTS: A total of seven patients with COVID-19 who had one or more positive respiratory cultures for Aspergillus fumigatus were identified, all of whom were mechanically ventilated in the ICU. Four patients were classified as putative IPA. The median age was 79 years, and all patients were male. The patients had been mechanically ventilated for a mean of 6.8 days (range: 1-14 days) before Aspergillus isolation. Serum galactomannan level was positive for only one patient. The majority of our cases received much higher doses of glucocorticoids than the dosage with a proven mortality benefit. All four patients died. CONCLUSIONS: Vigilance for secondary fungal infections will be needed to reduce adverse outcomes in critically ill patients with COVID-19.

Association Between CD4+, Viral Load, and Pulmonary Function in HIV.

PURPOSE: The antiretroviral therapy era has shifted the epidemiology of HIV-associated diseases, increasing the recognition of non-infectious pulmonary complications secondary to HIV. We aimed to determine the association between CD4+, viral load, and pulmonary function in individuals with uncontrolled HIV, and determine how changes in these parameters are associated with pulmonary function longitudinally. METHODS: This is a retrospective observational study of individuals with HIV who underwent pulmonary function testing in an urban medical center between August 1997 and November 2015. RESULTS: Of the 146 participants (mean age 52 ± 10 years), 49% were Hispanic, 56% were men, and 44% were current smokers. CD4+ <200 cells/µl was associated with significant diffusion impairment compared to CD4+ ≥200 cells/µl (DLCO 56 vs. 70%, p = <0.01). VL (viral load) ≥75 copies/ml was associated with significant diffusion impairment compared to VL <75 copies/ml (DLCO 60 vs. 71%, p = <0.01). No difference in FEV1, FEV1/FVC, or TLC was noted between groups. In univariate analysis, CD4+ and VL correlated with DLCO (r = +0.33; p = <0.01; r = -0.26; p = <0.01) and no correlation was noted with FEV1, FEV1/FVC, or TLC. Current smoking and history of AIDS correlated with DLCO (r = -0.20; p = 0.03; r = -0.20; p = 0.04). After adjusting for smoking and other confounders, VL ≥75 copies/ml correlated with a 11.2 (CI 95% [3.03-19.4], p = <0.01) decrease in DLCO. In Spearman's Rank correlation, there was a negative correlation between change in VL and change in DLCO over time (ρ = -0.47; p = <0.01). CONCLUSION: The presence of viremia in individuals with HIV is independently associated with impaired DLCO. Suppression of VL may allow for recovery in diffusing capacity over time, though the degree to which this occurs requires further investigation.

Behavioral intervention improves treatment outcomes among HIV-infected individuals who have delayed, declined, or discontinued antiretroviral therapy: a randomized controlled trial of a novel intervention.

Nationally up to 60 % of persons living with HIV are neither taking antiretroviral therapy (ART) nor well engaged in HIV care, mainly racial/ethnic minorities. This study examined a new culturally targeted multi-component intervention to address emotional, attitudinal, and social/structural barriers to ART initiation and HIV care. Participants (N = 95) were African American/Black and Latino adults with CD4 < 500 cells/mm(3) not taking ART, randomized 1:1 to intervention or control arms, the latter receiving treatment as usual. Primary endpoints were adherence, evaluated via ART concentrations in hair samples, and HIV viral load suppression. The intervention was feasible and acceptable. Eight months post-baseline, intervention participants tended to be more likely to evidence "good" (that is, 7 days/week) adherence (60 vs. 26.7 %; p = 0.087; OR = 3.95), and had lower viral load levels than controls (t(22) = 2.29, p = 0.032; OR = 5.20), both large effect sizes. This highly promising intervention merits further study.

A true challenge: Disseminated tuberculosis with tuberculous meningitis in a patient with underlying chronic liver disease.

Tuberculous meningitis (TBM) is a potentially life-threatening form of tuberculosis (TB) that affects the central nervous system. Its management in patients with concomitant chronic liver disease (CLD) presents unique challenges due to altered drug metabolism with potentially impaired spinal fluid drug penetration and hepatotoxicity. The standard regimen for TBM includes isoniazid (INH) and rifampin (RIF), and Pyrazinamide (PZA) which are metabolized by the liver and may cause hepatotoxicity, which can exacerbate preexisting liver disease. Thus, careful consideration is required to balance therapeutic efficacy with potential drug-induced hepatotoxicity. Regular monitoring of liver function tests and clinical response is essential to minimize adverse effects and optimize treatment outcomes. Further research is needed to establish evidence-based guidelines for the tailored management of TBM in this vulnerable patient subset. Overall, the treatment of TBM in patients with severe liver disease should be individualized and closely monitored.

A Coronavirus Disease 2019 (COVID-19) Mystery: Persistent Fevers and Leukocytosis in a Patient With Severe COVID-19.

Short-course glucocorticosteroids are being used and tocilizumab (TCZ) had been used to treat patients with severe coronavirus disease 2019 (COVID-19) disease. These agents, when administered individually, have been associated with tuberculosis (TB) during chronic use. We report a case of TB in a 44-year-old male with diabetes and severe COVID-19 who received high-dose short-course glucocorticosteroids and a single dose of TCZ. The clinical presentation was atypical with unresolving fevers and leukocytosis, progressive lower lobe cavities, and hilar adenopathy. Delayed diagnosis led to prolonged hospitalization and extensive antibiotic use.

A case of cutaneous metastasis mimicking herpes zoster rash.

Cutaneous metastasis is a rare occurrence and often is confused with infectious etiology most commonly herpes zoster rash. We present a case 49 year old male with history of metastatic colon cancer with persistent dermatomal vesicular rash that thought to be due to herpes zoster. A skin biopsy eventually revealed malignant cells.

Varicella-zoster virus (VZV) multifocal vasculopathy in a patient with systemic lupus erythematosus - a diagnostic and treatment dilemma.

Cerebral vasculopathy due to varicella-zoster virus (VZV) infection is well-documented. We report a fatal case of VZV multifocal vasculopathy in a patient with systemic lupus erythematosus (SLE) who presented with subacute changes in mental status and had multiple areas of hemorrhagic infarcts on brain imaging. However, the correct diagnosis was delayed by several confounding factors including the absence of zoster rash, normal cerebral angiography, persistently low cerebrospinal fluid (CSF) glucose and negative initial polymerase chain reaction (PCR) for VZV DNA in the CSF. Our case and literature review suggests that the sensitivity of PCR for VZV DNA in the CSF is low in VZV vasculopathy and clinical suspicion of this disease in the setting of characteristic imaging findings could be crucial to timely diagnosis.

Exploring How Substance Use Impedes Engagement along the HIV Care Continuum: A Qualitative Study.

Drug use is associated with low uptake of HIV antiretroviral therapy (ART), an under-studied step in the HIV care continuum, and insufficient engagement in HIV primary care. However, the specific underlying mechanisms by which drug use impedes these HIV health outcomes are poorly understood. The present qualitative study addresses this gap in the literature, focusing on African-American/Black and Hispanic persons living with HIV (PLWH) who had delayed, declined, or discontinued ART and who also were generally poorly engaged in health care. Participants (N = 37) were purposively sampled from a larger study for maximum variation on HIV indices. They engaged in 1-2 h audio-recorded in-depth semi-structured interviews on HIV histories guided by a multilevel social-cognitive theory. Transcripts were analyzed using a systematic content analysis approach. Consistent with the existing literature, heavy substance use, but not casual or social use, impeded ART uptake, mainly by undermining confidence in medication management abilities and triggering depression. The confluence of African-American/Black or Hispanic race/ethnicity, poverty, and drug use was associated with high levels of perceived stigma and inferior treatment in health-care settings compared to their peers. Furthermore, providers were described as frequently assuming participants were selling their medications to buy drugs, which strained provider-patient relationships. High levels of medical distrust, common in this population, created fears of ART and of negative interactions between street drugs and ART, but participants could not easily discuss this concern with health-care providers. Barriers to ART initiation and HIV care were embedded in other structural- and social-level challenges, which disproportionately affect low-income African-American/Black and Hispanic PLWH (e.g., homelessness, violence). Yet, HIV management was cyclical. In collaboration with trusted providers and ancillary staff, participants commonly reduced substance use and initiated or reinitiated ART. The present study highlights a number of addressable barriers to ART initiation and engagement in HIV care for this vulnerable population, as well as gaps in current practice and potential junctures for intervention efforts.

The clinical pharmacokinetics of rifampin and ethambutol in HIV-infected persons with tuberculosis.

BACKGROUND: The pharmacokinetics of rifampin and ethambutol in HIV-infected patients with tuberculosis (TB) are incompletely characterized. We examined the pharmacokinetics of rifampin and ethambutol in a cohort of patients with HIV-related TB who were treated in the United States. METHODS: Serum drug concentrations were determined 2, 6, and 10 h after dosing in 36 HIV-infected patients with TB who were taking rifampin and in 49 who were taking ethambutol. Observed serum concentrations were compared with published normal ranges and published data. RESULTS: With daily dosing of rifampin (600 mg), 26 (77%) of 34 patients (95% confidence interval [CI], 59%-89%]) had a low maximum concentration of rifampin (<8 microg/mL), and 12 (35%; 95% CI, 20%-54%) had a very low maximum concentration (<4 microg/mL). With intermittent rifampin dosing (600 mg), 13 (68%) of 19 patients (95% CI, 44%-85%) had a low maximum concentration of rifampin, and 5 (26%; 95% CI, 11%-50%) had a very low maximum concentration. With daily ethambutol dosing (20 mg/kg), 33 (69%) of 48 patients (95% CI, 55%-81%) had a low maximum concentration of ethambutol (<2 microg/mL), and 18 (38%; 95% CI, 24%-53%) had a very low maximum concentration (<1 microg/mL). With intermittent ethambutol dosing (50 mg/kg twice weekly or 30 mg/kg thrice weekly), 13 (72%) of 18 patients (95% CI, 47%-88%) had a low maximum concentration of ethambutol (<4 microg/mL), and 5 (28%; 95% CI, 12%-54%]) had a very low maximum concentration (<2 microg/mL). CONCLUSIONS: In HIV-infected patients with TB who are receiving rifampin and ethambutol, low maximum concentrations of rifampin and ethambutol were common. For patients with HIV-related TB, therapeutic monitoring of rifampin and ethambutol levels may help clinicians achieve target serum concentrations.

The clinical pharmacokinetics of pyrazinamide in HIV-infected persons with tuberculosis.

The pharmacokinetics of pyrazinamide (PZA) in patients with human immunodeficiency virus (HIV)-related tuberculosis are incompletely characterized. Serum PZA concentrations were determined at 2, 6, and 10 h after dosing in 48 subjects with HIV-related tuberculosis. Estimates of drug exposure using 2-h concentrations and 2- and 3-time point estimates of area under time-concentration curves (AUCs) were compared. For daily dosing, 2-h concentrations less than low and very low literature-defined cut points (i.e., 20 and 10 mg/L) were noted for 2 subjects (4%) and 1 subject (2%), respectively. For intermittent PZA dosing, 1 subject (4%) had a 2-h concentration that was less than the low cut point (25 mg/L). Correlations between 2-h concentration and AUC estimates based on 2- or 3-time point concentration determinations were strong. In HIV-infected persons receiving antituberculosis regimens containing PZA, lower-than-expected 2-h concentrations are uncommon. For therapeutic monitoring of PZA drug exposure, determination of a 2-h postdose concentration appears as reliable as 2- or 3-time point estimates of the AUC for PZA.

Rapid loss of vaccine-acquired hepatitis B surface antibody after three doses of hepatitis B vaccination in HIV-infected persons.

HIV-infected individuals have poor responses to hepatitis B vaccine and may have decreased durability of post-vaccination immunity. Retrospective chart review was conducted for HIV-1 positive individuals aged ≥18 years who received hepatitis B vaccine at an urban HIV clinic. A total of 309 patients completed three doses and 178 had post-vaccine serology testing after the third dose. In multivariate analysis, time between the third dose and the first post-vaccine serology testing at 180-359 days (OR = 0.077, p = 0.049) and at ≥360 days (OR = 0.065, p = 0.019) were associated with poor vaccine responses. A significant decrease in seropositivity appeared as early as 180 days after the third vaccine dose, suggesting a rapid loss of vaccine-acquired hepatitis B surface antibody in HIV-infected persons. Our findings suggest that hepatitis B surface antibody should be tested at 6 to 12 months after completing primary vaccine series in order to detect early secondary vaccine failure.

HIV-Infected Individuals Who Delay, Decline, or Discontinue Antiretroviral Therapy: Comparing Clinic- and Peer-Recruited Cohorts.

A substantial proportion of persons living with HIV/AIDS (PLHA) delay, decline, or discontinue antiretroviral therapy (ART) when it is medically indicated (40-45%), largely African-Americans and Latinos/Hispanics. This study explores the feasibility of locating PLHA, who are not on ART (PLHA-NOA) through clinics and peer-referral; compares the two cohorts on multi-level barriers to ART; and examines readiness to initiate/reinitiate ART, a predictor of treatment outcomes. We recruited adult HIV-infected African-American and Latino/Hispanic PLHA-NOA through HIV hospital clinics and peer-referral in 2012-2013. Participants were engaged in structured 1-h assessments with reliable/valid measures on barriers to ART. We found that recruitment through peers (63.2%, 60/95) was more feasible than in clinics (36.8%, 35/90). Participants were 48.0 years old and had lived with HIV for 14.7 years on average, and 56.8% had taken ART previously. Most (61.1%) were male and African-American (76.8%), and 23.2% were Latino/Hispanic. Peer-recruited participants were older, had lived with HIV longer, were less engaged in HIV care, and were more likely to have taken ART previously. The cohorts differed in reasons for discontinuing ART. Levels of ART knowledge were comparable between cohorts (68.5% correct), and there were no differences in attitudes toward ART (e.g., mistrust), which were in the neutral range. In bivariate linear regression, readiness for ART was negatively associated with physician mistrust (B = -10.4) and positively associated with self-efficacy (B = 5.5), positive outcome expectancies (B = 6.3), beliefs about personal necessity of ART (B = 17.5), and positive internal norms (B = 7.9). This study demonstrates the feasibility of engaging this vulnerable population through peer-referral. Peer-recruited PLHA evidence particularly high rates of risk factors compared to those in hospital clinics. Interventions to support ART initiation and continuation are sorely needed for both subgroups.

Modified directly observed antiretroviral therapy compared with self-administered therapy in treatment-naive HIV-1-infected patients: a randomized trial.

BACKGROUND: Success of antiretroviral therapy depends on high rates of adherence, but few interventions are effective. Our objective was to determine if modified directly observed therapy (mDOT) improves initial antiretroviral success. METHODS: In an open-label, randomized trial comparing mDOT (Monday-Friday for 24 weeks) and self-administered therapy with lopinavir/ritonavir soft gel capsules (800 mg/200 mg), emtricitabine (200 mg), and either extended-release stavudine (100 mg) or tenofovir (300 mg), all taken once daily, 82 participants received mDOT and 161, self-administered therapy. Participant eligibility included a plasma human immunodeficiency virus RNA level higher than 2000 copies/mL and being naïve to antiretroviral therapy. A total of 243 participants were predominantly male (79%) (median age, 38 years), with 84 Latinos (35%), 74 non-Latino blacks (30%), and 79 non-Latino whites (33%). The study was conducted at 23 AIDS Clinical Trials Group (ACTG) sites in the United States and 1 site in South Africa between October 2002 and January 2006. The primary outcome was virologic success at week 24 and secondary outcomes were virologic success, clinical progression, and adherence at week 48. RESULTS: Over 24 weeks, mDOT had greater virologic success (0.91; 95% confidence interval [CI], 0.81 to 0.95) than self-administered therapy (0.84; 95% CI, 0.77 to 0.89), but the difference (0.07; lower bound 95% CI, -0.01) did not reach the prespecified threshold of 0.075. Over 48 weeks, virologic success was not significantly different between mDOT (0.72; 95% CI, 0.61 to 0.81) and self-administered therapy (0.78; 95% CI, 0.70 to 0.84) (difference, -0.06; 95% CI, -0.18 to 0.07 [P = .19]). CONCLUSIONS: The potential benefit of mDOT was marginal and not sustained after discontinuation. Modified DOT should not be incorporated routinely for care of treatment-naïve human immunodeficiency virus type 1-infected patients.

Mycobacterial Infections of the Head and Neck.

Mycobacteria are important causes of head and neck infections. Mycobacterial lymphadenitis may be caused by both Mycobacterium tuberculosis and a variety of nontuberculous myocbacteria. Changes in the epidemiology of tuberculosis have caused a shift of the peak age range of tuberculous lymphadenitis from childhood to ages 20 to 40 years. Short-course chemotherapy is highly effective. Mycobacterium avium has become the most common cause of nontuberculous lymphadenitis, but new mycobacterial species are increasingly recognized. Treatment consists primarily of complete surgical excision, although roles for antimycobacterial chemotherapy are being identified. Transient flares of mycobacterial lymphadenitis, which occur during initiation of antituberculous therapy and in HIV-infected patients after initiation of antiretroviral therapy, may respond to short courses of corticosteroids. Tuberculous otitis media has become uncommon. Otitis media due to nontuberculous mycobacterial infection is increasingly seen in patients with pre-existing ear disease and after surgical and otic interventions. Tuberculosis of the eye has also become uncommon but may occur via hematogenous dissemination or direct innoculation. Nontuberculous mycobacteria, most commonly Mycobacterium chelonae and Mycobacterium fortuitum, may cause keratitis, usually after some form of corneal trauma.

Impact of monetary incentives on adherence to referral for screening chest x-rays after syringe exchange-based tuberculin skin testing.

INTRODUCTION: Syringe-exchange programs (SEPs) have proven to be valuable sites to conduct tuberculin skin testing among active injection drug users. Chest x-rays (CXRs) are needed to exclude active tuberculosis prior to initiating treatment for latent tuberculosis infection. Adherence of drug users to referral for off-site chest x-rays has been incomplete. Previous cost modeling demonstrated that a monetary incentive to promote adherence could be justified on the cost basis if it had even a modest effect on adherence. METHODS: We compared adherence to referral for chest x-rays among injection drug users undergoing syringe exchange-based tuberculosis screening in New York City before and after the implementation of monetary incentives. RESULTS: From 1995 to 1998, there were 119 IDUs referred for CXRs based on tuberculin skin testing at the SEP. From 1999 to 2001, there were 58 IDUs referred for CXRs with a $25 incentive based on adherence. Adherence to CXR referral within 7 days was 46/58 (79%) among individuals who received the monetary incentive versus 17/119 (14%) prior to the implementation of the monetary incentive (P<.0001; odds ratio [OR]=23; 95% confidence interval [CI]=9.5-57). The median time to obtaining a CXR was significantly shorter among those given the incentive than among those referred without the incentive (2 vs. 11 days, P<.0001). In multivariate logistic regression analysis, use of the incentive was highly independently associated with increased adherence (OR=22.9; 95% CI=10-52). CONCLUSIONS: Monetary incentives are highly effective in increasing adherence to referral for screening CXRs to exclude active tuberculosis after syringe exchange-based tuberculin skin testing. Prior cost modeling demonstrated that monetary incentives could be justified on the cost basis if they had even a modest effect on adherence. The current data demonstrated that monetary incentives are highly effective at increasing adherence in this setting and therefore are justifiable on a cost basis. When health care interventions for drug users require referral off site, monetary incentives may be particularly valuable in promoting adherence.