Design and methods of a randomized trial testing "Advancing care for COPD in people living with HIV by implementing evidence-based management through proactive E-consults (ACHIEVE)".

Chronic obstructive pulmonary disease (COPD) is one of the most common comorbid diseases among aging people with HIV (PWH) and is often mismanaged. To address this gap, we are conducting the study, "Advancing care for COPD in people living with HIV by Implementing Evidence-based management through proactive E-consults (ACHIEVE)." This intervention optimizes COPD management by promoting effective, evidence-based care and de-implementing inappropriate therapies for COPD in PWH receiving care at Veteran Affairs (VA) medical centers. Study pulmonologists are proactively supporting ID providers managing a population of PWH who have COPD, offering real-time evidence-based recommendations tailored to each patient. We are leveraging VA clinical and informatics infrastructures to communicate recommendations between the study team and clinical providers through the electronic health record (EHR) as an E-consult. If effective, ACHIEVE could serve as a model of effective, efficient COPD management among PWH receiving care in VA. This paper outlines the rationale and methodology of the ACHIEVE trial, one of a series of studies funded by the National Heart, Lung, and Blood Institute (NHLBI) within the ImPlementation REsearCh to DEvelop Interventions for People Living with HIV (PRECluDE) consortium to study chronic disease comorbidities in HIV populations.

The association between comorbidities and coronavirus disease 2019 hospitalization among people with HIV differs by age.

OBJECTIVES: To determine whether factors associated with coronavirus disease 2019 (COVID-19) hospitalization among people with HIV (PWH) differ by age stratum. DESIGN: Retrospective cohort study. METHODS: All adult PWH with a positive SARS-CoV-2 PCR in a public safety-net health system between 1 March 2020 and 28 February 2021 and a Veterans Affairs Medical Center between 1 1 March 2020 and 15 November 2020 in Atlanta, Georgia were included. We performed multivariable logistic regression to determine demographic and clinical factors associated with COVID-19 hospitalization overall and stratified by age less than 50 and at least 50 years. RESULTS: Three hundred and sixty-five PWH (mean age 49 years, 74% cisgender male, 82% black) were included. Ninety-six percent were on antiretroviral therapy (ART), 87% had CD4 + T-cell count at least 200 cells/µl, and 89% had HIV-1 RNA less than 200 copies/ml. Overall, age [adjusted odds ratio (aOR) 95% confidence interval (CI) 1.07 (1.04-1.10)], later date of SARS-CoV-2 infection [aOR 0.997 (0.995-1.00)], heart disease [aOR 2.27 (1.06-4.85)], and history of hepatitis C virus (HCV) [aOR 2.59 (1.13-5.89)] were associated with COVID-19 hospitalization. Age-adjusted comorbidity burden was associated with 30% increased risk of hospitalization [aOR 1.30 (1.11-1.54)]. Among 168 PWH less than 50 years old, older age [aOR 1.09 (1.01-1.18)] and no ART use [aOR 40.26 (4.12-393.62)] were associated with hospitalization; age-adjusted comorbidity burden was not ( P  = 0.25). Among 197 PWH at least 50, older age [aOR 1.10 (1.04-1.16)], heart disease [aOR 2.45 (1.04-5.77)], history of HCV [aOR 3.52 (1.29-9.60)], and age-adjusted comorbidity burden [aOR 1.36 (1.12-1.66)] were associated with hospitalization. CONCLUSION: Comorbidity burden is more strongly associated with COVID-19 hospitalization among older, rather than younger, PWH. These findings may have important implications for risk-stratifying COVID-19 therapies and booster recommendations in PWH.

Trends in Cause-Specific Mortality Among Veterans With HIV: A 35-Year (1982-2016) Analysis of the HIV Atlanta VA Cohort Study.

BACKGROUND: Causes of death and their trends among veterans with HIV (VWH) are different than those in the general population with HIV, but this has not been fully described. The objective was to understand the trends in, and risk factors for, all-cause and cause-specific mortality across eras of combination antiretroviral therapy (cART) among VWH. SETTING: The HIV Atlanta VA Cohort Study includes all VWH who ever sought care at the Atlanta VA Medical Center. METHODS: Age-adjusted all-cause and cause-specific mortality rates were calculated annually and compared between pre-cART (1982-1996), early-cART (1997-2006), and late-cART (2007-2016) eras. Trends were assessed using Kaplan-Meier curves, cumulative incidence functions, and joinpoint regression models. Risk factors were identified by Cox proportional hazards models. RESULTS: Of the 4674 VWH in the HIV Atlanta VA Cohort Study, 1752 died; of whom, 1399 (79.9%), 301 (17.2%), and 52 (3.0%) were diagnosed with HIV in the pre-cART, early-cART, and late-cART eras, respectively. Significant increases were observed in rates of all-cause, AIDS-related, and non-AIDS-related mortality in the pre-cART era, followed by declines in the early-cART and late-cART eras. All-cause, AIDS-related, and non-AIDS-related mortality rates plummeted by 65%, 81%, and 45%, respectively, from the pre-cART to late-cART eras. However, VWH continue to die at higher rates due to AIDS-related infections, non-AIDS-related malignancies, respiratory disease, cardiovascular disease, and renal failure than those in the general population with HIV. CONCLUSIONS: In older populations with HIV, it is important that providers not only monitor for and treat diseases associated with aging but also intervene and address lifestyle risk factors.

Using Active Surveillance to Identify Monoclonal Antibody Candidates Among COVID-19-Positive Veterans in the Atlanta VA Health Care System.

Background: Strategies for optimizing identification and outreach to potential candidates for monoclonal antibody (Mab) therapy for COVID-19 are not clear. Using a centralized, active surveillance system, the Atlanta Veterans Affairs Health Care System (AVAHCS) infectious disease (ID) team identified candidates for Mab infusion and provided treatment. Observations: As part of a quality improvement project from December 28, 2020, to August 31, 2021, a clinical team consisting of ID pharmacists and physicians reviewed each outpatient with a positive COVID-19 polymerase chain reaction test daily at the AVAHCS. The clinical team used Emergency Use Authorization (EUA) criteria to determine eligibility. Eligible patients were contacted on the same day of review via telephone to confirm eligibility and obtain verbal consent. Telehealth follow-up occurred on day 1 and day 7 postinfusion to assess for adverse events. In total, 2028 patients with COVID-19 were identified; 289 patients (14%) were eligible, and 132 (46%) received Mab therapy. Similar to AVAHCS demographics, a majority of those who received Mab therapy were non-Hispanic Black patients (65%). The most common comorbidities were hypertension (59%) and diabetes (37%). The median time from symptom onset to positive COVID-19 polymerase chain reaction (PCR) test result was 6 days (range, 0-9), and the median time from positive COVID-19 PCR test result to Mab infusion was 2 days (range, 0-8). Twelve patients (9%) required hospitalization for worsening COVID-19 symptoms postinfusion. No deaths occurred. Conclusions: Combining laboratory surveillance and active screening led to high uptake of Mab therapy and minimized delay from symptom onset to Mab infusion, thereby optimizing outpatient treatment of COVID-19. This approach also successfully screened and treated Black patients in the AVAHCS population.

Clinical characteristics and social determinants of health associated with 30-day hospital readmissions of patients with COVID-19.

COVID-19 readmissions are associated with increased patient mortality and healthcare system strain. This retrospective cohort study of PCR-confirmed COVID-19 positive adults (>18 years) hospitalized and readmitted within 30 days of discharge from index admission was performed at eight Atlanta hospitals from March to December 2020. The objective was to describe COVID-19 patient-level demographics and clinical characteristics, and community-level social determinants of health (SDoH) that contribute to 30-day readmissions. Demographics, comorbidities, COVID-19 treatment, and discharge disposition data were extracted from the index admission. ZIP codes were linked to a demographic/lifestyle database interpolating to community-level SDoH. Of 7155 patients with COVID-19, 463 (6.5%) had 30-day, unplanned, all-cause hospital readmissions. Statistically significant differences were not found in readmissions stratified by age, sex, race, or ethnicity. Patients with a high-risk Charlson Comorbidity Index had higher odds of readmission (OR 4.8 (95% CI: 2.1 to 11.0)). Remdesivir treatment and intensive care unit (ICU) care were associated with lower odds of readmission (OR 0.5 (95% CI: 0.4 to 0.8) and OR 0.5 (95% CI: 0.4 to 0.7), respectively). Patients residing in communities with larger average household size were less likely to be readmitted (OR 0.7 (95% CI: 0.5 to 0.9). In this cohort, patients who received remdesivir, were cared for in an ICU, and resided in ZIP codes with higher proportions of residents with increased social support had lower odds of readmission. These patient-level factors and community-level SDoH may be used to identify patients with COVID-19 who are at increased risk of readmission.

Rapid Antiretroviral Therapy Program: Development and Evaluation at a Veterans Affairs Medical Center in the Southern United States.

Early HIV viral suppression (VS) improves individual health outcomes and decreases onward transmission. We designed an outpatient clinic protocol to rapidly initiate antiretroviral therapy (ART) in a large Veterans Health Administration (VA) HIV clinic. A pre-post evaluation was performed using a retrospective cohort study design for new diagnoses of HIV infection from January 2012 to February 2020. Time-to-event analyses were performed using the Cox proportional hazards model with the intervention group as the main exposure adjusted for integrase inhibitor usage, baseline viral load, age, gender, and race. Most of the patients were men (historical control: 94.8%, n = 55; Rapid Start: 94.8%, n = 55) and Black or African American persons (historical control: 87.9%, n = 51; Rapid Start: 82.8%, n = 48). More patients initiated treatment with an integrase inhibitor-based regimen in the Rapid Start group (98.3%, n = 57) compared with the historical control group (39.7%, n = 23). Compared with controls, the Rapid Start patients were significantly more likely to achieve VS at any given time during the study period (hazard ratio 2.65; p < 0.001). Median days (interquartile range) from diagnosis to VS decreased from 180.5 (102.5-338.5) to 62 (40-105) (p < 0.001), first appointment to VS decreased from 123 (68.5-237.5) to 45 (28-82) (p < 0.001), referral to first visit decreased from 20 (10-43) to 1 (0-3) (p < 0.001), and from first visit to ART dispense date decreased from 27.5 (3-50) to 0 (0-0) (p = 0.01). Prioritizing immediate ART initiation can compress the HIV care continuum from diagnosis to linkage to VS. Implementation of the Rapid Start Protocol should be considered at all VA facilities providing HIV care.

Use of Baricitinib in Patients With Moderate to Severe Coronavirus Disease 2019.

Hyperinflammation is associated with increased mortality in coronavirus disease 2019 (COVID-19). In this retrospective, uncontrolled patient cohort with moderate -severe COVID-19, treatment with baricitinib plus hydroxychloroquine was associated with recovery in 11 of 15 patients. Baricitinib for the treatment of COVID-19 should be further investigated in randomized, controlled clinical trials.

Clinical characteristics, comorbidities and outcomes among persons with HIV hospitalized with coronavirus disease 2019 in Atlanta, Georgia.

BACKGROUND: There are limited data describing the presenting characteristics and outcomes among US persons with HIV (PWH) requiring hospitalization for coronavirus disease 2019 (COVID-19). METHODS: We performed a case series of all PWH sequentially admitted with COVID-19 from 8 March 2020 to 23 April 2020 at three hospitals in Atlanta, Georgia. Sociodemographic, clinical and HIV-associated characteristics were collected. RESULTS: Of 530 confirmed COVID-19 cases hospitalized during this period, 20 occurred among PWH (3.8%). The median age was 57 (Q1-Q3, 48-62) years, 65% were men, and 85% were non-Hispanic Black. Presenting median symptom duration was 5 (Q1-Q3, 3-7) days; cough (90%), fever (65%), malaise (60%) and dyspnea (60%) were most common. On admission, 40% of patients required oxygenation support and 65% had an abnormal chest radiograph. Median length of hospitalization was 5 (Q1-Q3, 4-12) days, 30% required intensive care, 15% required intubation, and 15% died. Median CD4 cell count prior to admission was 425 (Q1-Q3, 262-815) cells/µl and 90% of patients had HIV-1 RNA less than 200 copies/ml. Half of the patients had at least five comorbidities; hypertension (70%), dyslipidemia (60%) and diabetes (45%) were most prevalent. All three patients who died had CD4 cell count more than 200, HIV suppression and each had a total of five comorbidities. CONCLUSION: The multisite series in the Southern United States provides characteristics and early outcomes of hospitalized PWH with COVID-19. Nearly all patients had controlled HIV and a high comorbidity burden. Additional study of COVID-19 among PWH is needed to determine the role of age, comorbidities and HIV control in mediating COVID-19 presentation and its sequelae.

Low Rates of Vaccination for Herpes Zoster in Older People Living With HIV.

Herpes zoster (HZ) occurs at a higher age-specific rate in people living with HIV (PLWH) than in the general population. We implemented a quality improvement study to assess herpes zoster vaccine (HZV) usage among PLWH, assess HZV usage after additional reminders/prompts, and identify barriers to HZV among older PLWH. HZV rates in PLWH were determined in six institutions with varying payment structures. For the intervention, Part 1, PLWH eligible for HZV at the University of Colorado were identified, and providers were notified of patient eligibility. In Part 2, in addition to provider notification, an order for HZV was placed in the patient's chart before a clinic appointment. HZ vaccination rates ranged from 1.5% to 42.4% at six sites. Before the intervention, 21.3% of eligible University of Colorado patients had received HZV. An additional 8.3% received HZV with Part 1 and 17.8% with Part 2 interventions. At completion, a total of 53.2% of eligible patients had received HZV through routine clinical care or the interventions. Insurance coverage concern was cited as a common reason for not receiving HZV. Minor adverse reactions occurred in 26.7% patients and did not require medical care. HZV coverage was low at a majority of sites. Clinical reminders with links to vaccination orders or preplaced vaccination orders led to improved HZV coverage in our clinic, but published guidelines for use of HZV in PLWH and improvement in logistic or insurance barriers to HZV receipt are paramount to improved HZV coverage.

Retention in HIV care depends on patients' perceptions of the clinic experience.

Institutional barriers in HIV primary care settings can contribute substantially to disparities in retention in HIV treatment and HIV-related outcomes. This qualitative study compared the perceptions of clinic experiences of persons living with HIV (PLWH) in a Veterans Affairs HIV primary care clinic setting who were retained in care with the experiences of those who were not retained in care. Qualitative data from 25 in-depth interviews were analyzed to identify facilitators and barriers to retention in HIV care. Results showed that participants not retained in care experienced barriers to retention involving dissatisfaction with clinic wait times, low confidence in clinicians, and customer service concerns. For participants retained in care, patience with procedural issues, confidence in clinicians, and interpersonal connections were factors that enhanced retention despite the fact that these participants recognized the same barriers as those who were not retained in care. These findings can inform interventions aimed at improving retention in HIV care.

Decreasing incidence of herpes zoster in the highly active antiretroviral therapy era.

We evaluated the effect of highly active antiretroviral therapy (HAART) on the incidence of herpes zoster (HZ) in human immunodeficiency virus (HIV)-infected subjects. The annual incidence of HZ per 100 person-years decreased significantly from 6.3 episodes in 1987 to 1.0 episode in 2011, probably reflecting improved immune function.

The rise and fall of methicillin-resistant Staphylococcus aureus infections in HIV patients.

We evaluated the annual and weighted incidence of methicillin-resistant Staphylococcus aureus infections by specific risk factors in a prospective cohort of HIV patients. We found 228 infections in 167 patients from 2002 to 2009. Higher rates were seen in men who have sex with men and intravenous drug users, patients with lower CD4 cell counts, patients not on antiretrovirals and younger patients. The annual incidence peaked in 2007 and has decreased since.

Increasing incidence of herpes zoster among Veterans.

BACKGROUND: The incidence of herpes zoster in the United States has been estimated to be > or =1 million cases annually, with a higher rate in adults older than 60 years. The morbidity of the disease, including postherpetic neuralgia, imposes significant effects on quality of life. We analyzed reports of herpes zoster in the Veterans Affairs (VA) population because these patients are older and could provide a reflection of disease trends in the aging US population. These data will provide a baseline for future analyses of the incidence of herpes zoster after the introduction of the herpes zoster vaccine in late 2007. METHODS: To evaluate the trend in the annual incidence of herpes zoster for fiscal year 2000 (beginning October 1999) through fiscal year 2007 (through September 2007), we derived incidence rates using the Veterans Health Administration Decision Support System reports of herpes zoster by International Classification of Diseases, Ninth Revision codes from 2000 through 2007 and the corresponding denominator data for all veterans in care. These rates were validated by review of medical records of patients with diagnoses of herpes zoster at the Atlanta VA Medical Center. RESULTS: The annual incidence of herpes zoster increased from 3.10 episodes per 1000 veterans in 2000 to 5.22 in 2007 (R(2)=0.9743; P<.001). This increasing rate was seen in both men and women but only in groups older than 40 years. CONCLUSION: The increasing incidence of herpes zoster in our veteran population and its effect on the quality of life of the veterans validate the need for improved rates of vaccination in this population.

Viral infections associated with haemophagocytic syndrome.

Haemophagocytic syndrome (HPS) or haemophagocytic lymphohistiocytosis (HLH) is a rare disease caused by a dysfunction of cytotoxic T cells and NK cells. This T cell/NK cell dysregulation causes an aberrant cytokine release, resulting in proliferation/activation of histiocytes with subsequent haemophagocytosis. Histiocytic infiltration of the reticuloendothelial system results in hepatomegaly, splenomegaly, lymphadenopathy and pancytopenia ultimately leading to multiple organ dysfunctions. Common clinical features include high fevers despite broad spectrum antimicrobials, maculopapular rash, neurological symptoms, coagulopathy and abnormal liver function tests. Haemophagocytic syndrome can be either primary, i.e. due to an underlying genetic defect or secondary, associated with malignancies, autoimmune diseases (also called macrophage activation syndrome) or infections. Infectious triggers are most commonly due to viral infections mainly of the herpes group, with EBV being the most common cause. HPS can be fatal if untreated. Early recognition of the clinical presentation and laboratory abnormalities associated with HPS and prompt initiation of treatment can be life saving. HPS triggered by viral infections generally does not respond to specific antiviral therapy but may be treated with immunosuppressive/immunomodulatory agents and, in refractory cases, with bone marrow transplantation.

Methicillin-resistant Staphylococcus aureus in HIV-infected patients.

Concordant with the emergence of methicillin-resistant Staphylococcus aureus (MRSA) in the community setting, colonization and infections with this pathogen have become a prevalent problem among the human immunodeficiency virus (HIV)-positive population. A variety of different host- and, possibly, pathogen-related factors may play a role in explaining the increased prevalence and incidence observed. In this article, we review pathophysiology, epidemiology, clinical manifestations, and treatment of MRSA in the HIV-infected population.

The AIDS resistance of naturally SIV-infected sooty mangabeys is independent of cellular immunity to the virus.

In contrast to human immunodeficiency virus (HIV)-infected humans, natural hosts for simian immunodeficiency virus (SIV) very rarely progress to acquired immunodeficiency syndrome (AIDS). While the mechanisms underlying this disease resistance are still poorly understood, a consistent feature of natural SIV infection is the absence of the generalized immune activation associated with HIV infection. To investigate the immunologic mechanisms underlying the absence of AIDS in SIV-infected sooty mangabeys (SMs), a natural host species, we performed a detailed analysis of the SIV-specific cellular immune responses in 110 SIV-infected SMs. We found that while SIV-specific T-cell responses are detectable in the majority of animals, their magnitude and breadth are, in fact, lower than what has been described in HIV-infected humans, both in terms of cytokine production (ie, IFN-gamma, TNF-alpha, and IL-2) and degranulation (ie, CD107a expression). Of importance, SIV-specific T-cell responses were similarly low when either SIVmac239-derived peptides or autologous SIVsmm peptides were used as stimuli. No correlation was found between SIV-specific T-cell responses and either viral load or CD4+ T-cell count, or between these responses and markers of T-cell activation and proliferation. These findings indicate that the absence of AIDS in naturally SIV-infected sooty mangabeys is independent of a strong cellular immune response to the virus.

Emphysematous cholecystitis due to Salmonella derby.

We present the case of a woman with diabetes mellitus who developed symptoms and signs consistent with gastroenteritis. After admission for hydration, the patient rapidly became critically ill and an abdominal catastrophe was suspected as the cause of her deterioration. Computed tomography of her abdomen was done and revealed gas in the lumen of the gallbladder consistent with emphysematous cholecystitis. She underwent emergent cholecystectomy, which revealed that the gallbladder had already ruptured. Blood cultures grew Salmonella derby. After a prolonged hospitalisation she eventually recovered and was discharged home. Emphysematous cholecystitis, thought to be a variant of acute cholecystitis, is a medical and surgical emergency. Diagnosis relies heavily on imaging findings by ultrasound or computed tomography since the clinical presentation is often non-specific. Cholecystectomy remains the treatment of choice in addition to broad spectrum antibiotics and other supportive measures.