Weight change with antiretroviral switch from integrase inhibitor or tenofovir alafenamide-based to Doravirine-Based regimens in people with HIV.

BACKGROUND: Weight gain has been well-described with integrase strand transfer inhibitors (INSTIs) and tenofovir alafenamide (TAF). Doravirine (DOR) has been identified as a relatively "weight-neutral" drug; however, there is little data describing its effect on weight change in routine clinical practice. METHODS: We conducted a retrospective chart review of weight change among people with HIV changing from an INSTI- to a non-INSTI regimen with DOR. RESULTS: At the time of ART switch, among 49 people with HIV, the mean age was 47 years, 24% were female, and 75% had HIV-1 viral load <200 copies/mL. Most (55%) people with HIV were taking bictegravir/TAF/emtricitabine prior to the switch. Although 84% switched due to concerns about weight gain, only 16% had a weight gain of ≥10% in the year preceding, and 49% had no substantial change in weight. 86% switched to DOR/lamivudine/tenofovir disoproxil fumarate. A weight decrease (-2.6% [95% CI: -5.1, -0.1%, p = .041] was seen over the year following the ART switch. Weight change prior to switch was greatest in the year 2021 compared to 2019, 2020, and 2022. CONCLUSIONS: Overall, modest changes in weight were seen following ART switch from INSTI-based regimen to a DOR-based, non-INSTI regimen. Further investigations with larger people with HIV cohorts will be helpful to guide clinical practice, while the impact of the COVID-19 pandemic on weight change should also be considered.

Previous corticosteroid exposure associates with an increased Pneumocystis jirovecii pneumonia mortality among HIV-negative patients: a global research network with a follow-up multicenter case-control study.

Background: HIV-negative patients have substantial mortality from Pneumocystis jirovecii pneumonia (PJP). We lack predictors of HIV-negative PJP-associated mortality. Objective: We aim to characterize the role of prior corticosteroid exposure in PJP-related mortality. Methods: We queried a global research network to identify adult HIV-negative patients with PJP with or without corticosteroid exposure in the preceding year before diagnosis (n = 8,021). We performed a propensity score-matched analysis to adjust baseline patient characteristics and analyzed outcomes. We follow-up the results with a multicenter ten years retrospective case-control cohort of HIV-negative patients tested for PJP by PCP Direct Fluorescent Antigen. We used a Cox proportional hazards model for survival analysis. Results: 1822 HIV-negative propensity-scored matched patients with prior corticosteroid exposure had significantly increased 10 weeks (16% versus 9%, p < 0.0001) and one-year mortality after PJP diagnosis (23% versus 14%, p < 0.0001). (1→3)-ß-D-glucan (197.6 ± 155.8 versus 63 ± 0 pg/ml, p = 0.014), ferritin levels (1227 ± 2486 versus 768 ± 1060 mcg/l, p = 0.047), lymphopenia (1.5 ± 1.5 versus 2.0 ± 1.6 103 cells/µl, p < 0.0001) and hypoxia (SatO2: 86.7% versus 91.6%, p < 0.0001) were higher or worse in those with prior steroid use. Patients who died were more likely to have previously received dexamethasone (35% versus 16%, p < 0.001) or prednisone (49% versus 29%, p < 0.001). Adjusted Cox proportional-hazard model validation showed an independently increased mortality at 10 weeks (HR: 3.7, CI: 1.5-9.2, p = 0.004) and 1 year (HR: 4.5, CI: 2.0-10.4, p < 0.0001) among HIV-negative patients with previous corticosteroid exposure. Conclusion: Preceding corticosteroids in HIV-negative patients with PJP are associated with higher mortality. A higher fungal burden may influence corticosteroid-mediated mortality. Assessment of PJP prophylaxis must become a standard clinical best practice when instituting corticosteroid therapy courses.

Investigating transmission of SARS-CoV-2 using novel face mask sampling: a protocol for an observational prospective study of index cases and their contacts in a congregate setting.

INTRODUCTION: This study aims to measure how transmission of SARS-CoV-2 occurs in communities and to identify conditions that lend to increased transmission focusing on congregate situations. We will measure SARS-CoV-2 in exhaled breath of asymptomatic and symptomatic persons using face mask sampling-a non-invasive method for SARS-CoV-2 detection in exhaled air. We aim to detect transmission clusters and identify risk factors for SARS-CoV-2 transmission in presymptomatic, asymptomatic and symptomatic individuals. METHODS AND ANALYSIS: In this observational prospective study with daily follow-up, index cases and their respective contacts are identified at each participating institution. Contact definitions are based on Centers for Disease Control and Prevention and local health department guidelines. Participants will wear masks with polyvinyl alcohol test strips adhered to the inside for 2 hours daily. The strips are applied to all masks used over at least 7 days. In addition, self-administered nasal swabs and (optional) finger prick blood samples are performed by participants. Samples are tested by standard PCR protocols and by novel antigen tests. ETHICS AND DISSEMINATION: This study was approved by the Colorado Multiple Institutional Review Board and the WHO Ethics Review Committee. From the data generated, we will analyse transmission clusters and risk factors for transmission of SARS-CoV-2 in congregate settings. The kinetics of asymptomatic transmission and the evaluation of non-invasive tools for detection of transmissibility are of crucial importance for the development of more targeted control interventions-and ultimately to assist with keeping congregate settings open that are essential for our social fabric. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (#NCT05145803).

Multiple-Dose Dalbavancin Regimens as the Predominant Treatment of Deep-Seated or Endovascular Infections: A Scoping Review.

Off-label use of dalbavancin for deep-seated and endovascular infections has been increasing. We performed a scoping review to evaluate the evidence for use of multiple-dose dalbavancin regimens as the predominant therapy for these indications. Predominant therapy was defined as use of dalbavancin without other concurrent antibiotics for more than half of the total treatment duration. Fifteen publications were identified; 2 were small, open-label randomized controlled trials and the remainder were retrospective observational studies or case reports. A total of 144 cases from these publications met eligibility criteria for inclusion in this review. Types of infections included osteoarticular infections, catheter-related or complicated bloodstream infections, and infective endocarditis. Overall, the evidence for use of multiple-dose regimens of dalbavancin for deep-seated and endovascular infections is limited by a paucity of data from controlled trials, heterogeneity of dosing regimens, and a lack of standardized clinical outcomes.

Experiences with Diagnosis and Treatment of Chagas Disease at a United States Teaching Hospital-Clinical Features of Patients with Positive Screening Serologic Testing.

Chagas disease (CD) is the third most common parasitic infection globally and can cause cardiac and gastrointestinal complications. Around 300,000 carriers of CD live in the U.S., with about 3000 of those in Colorado. We described our experience in diagnosing CD at a Colorado teaching hospital to revise screening eligibility criteria. From 2006 to 2020, we reviewed Trypanosoma cruzi (TC) IgG serology results for 1156 patients in our institution. We identified 23 patients (1.99%) who had a positive test. A total of 14/23 (60%) of positive serologies never had confirmatory testing, and 7 of them were lost to follow up. Confirmatory testing, performed in 9 patients, resulted in being positive in 3. One additional case of CD was identified by positive tissue pathology. All four confirmed cases were among patients born in Latin America. While most of the testing for CD at our institution is part of the pretransplant screening, no confirmed cases of CD derived from this strategy. Exposure risk in this population is not always documented, and initial positive results from screening are not always confirmed. The lack of standardized screening protocols for CD in our institution contributes to underdiagnosis locally and in health systems nationwide. Given a large number of individuals in the U.S. with chronic CD, improved screening is warranted.

Intramedullary spinal cord lesions in an immunocompromised host due to Mycobacterium haemophilum.

Mycobacterium haemophilum is a slow growing acid-fast bacillus (AFB) in the nontuberculous mycobacteria (NTM) group. M. haemophilum typically causes cervicofacial lymphadenitis in children, cutaneous diseases, septic arthritis and osteomyelitis. However, it rarely causes isolated spinal cord disease. We report the first case, to our knowledge, of isolated intramedullary spinal lesions secondary to M. haemophilum. This case involved a patient with newly diagnosed human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). He developed significant immune reconstitution inflammatory syndrome (IRIS) during his treatment. M. haemophilum should be on the differential for isolated intramedullary spinal lesions, particularly in immunocompromised patients. Given our patient's severe IRIS, patients with HIV and M. haemophilum infection should be closely monitored for IRIS and treated aggressively. In high risk circumstances such as M. haemophilum spinal disease in patients with HIV, clinicians should consider pre-emptive treatment for IRIS.

Boosted darunavir and dolutegravir dual therapy among a cohort of highly treatment-experienced individuals.

BACKGROUND: The use of dual antiretroviral therapy (ART) regimens for treatment of HIV is increasing. The contemporary combination of boosted darunavir with dolutegravir has not been widely studied. METHODS: This was a retrospective cohort study that evaluated treatment-experienced individuals within three large urban clinics prescribed boosted darunavir with dolutegravir (study regimen) dual therapy. Follow-up was defined as the number of days from regimen initiation until the last HIV RNA determination on the study regimen. Virological outcomes, HIV RNA ≤50 copies/ml (undetectable), were assessed overall and by baseline HIV RNA status. RESULTS: Of 65 individuals included, 83% were at least 3-class antiretroviral-experienced and median time since starting ART was 19 years (IQR 13-22). Median follow-up was 419 days (IQR 286-744). An undetectable HIV RNA was achieved by 62/65 (95%) individuals at any time point on the study regimen. At the end of follow-up 61/65 (94%) individuals remained undetectable, including 48/49 (98%) with an undetectable HIV RNA at baseline (those changing for optimization) and 13/16 (81%) with viraemia at baseline (those changing therapy during virological failure). At the end of follow-up, 55 (85%) individuals were still taking the study regimen. No individuals stopped therapy due to virological failure or intolerance. CONCLUSIONS: In a highly treatment-experienced cohort, boosted darunavir with dolutegravir dual therapy demonstrated high rates of virological success, even in those with detectable HIV RNA prior to initiating the study regimen. Further study of this potent, simple, high-barrier dual-class regimen is warranted.

Midlife adiposity predicts cognitive decline in the prospective Multicenter AIDS Cohort Study.

OBJECTIVE: Obesity is a common, modifiable cardiovascular and cerebrovascular risk factor. Among people with HIV, obesity may contribute to multisystem dysregulation including cognitive impairment. We examined body mass index (BMI) and central obesity (waist circumference [WC]) in association with domain-specific cognitive function and 10-year cognitive decline in men with HIV infection (MWH) vs HIV-uninfected (HIV-) men. METHODS: A total of 316 MWH and 656 HIV- Multicenter AIDS Cohort Study participants ≥40 years at baseline, with neuropsychological testing every 2 years and concurrent BMI and WC measurements, were included. MWH were included if taking ≥2 antiretroviral agents and had HIV-1 RNA <400 copies/mL at >80% of visits. Mixed-effects models included all visits from 1996 to 2015, stratified by HIV serostatus, and adjusted for sociodemographic, behavioral, and clinical characteristics. At baseline and follow-up, 8% of MWH and 15% of HIV- men and 41% of MWH and 56% of HIV- men were ≥60 years, respectively. RESULTS: Cross-sectionally, higher BMI was inversely associated with motor function in MWH and HIV- men, and attention/working memory in HIV- men. WC was inversely associated with motor function in MWH and HIV- men. Longitudinal associations indicated an obese BMI was associated with a less steep decline in motor function in MWH whereas in HIV- men, obesity was associated with a greater decline in motor function, learning, and memory. WC, or central obesity, showed similar patterns of associations. CONCLUSION: Higher adiposity is associated with lower cognition cross-sectionally and greater cognitive decline, particularly in HIV- men. Overweight and obesity may be important predictors of neurologic outcomes and avenues for prevention and intervention.

Herpes Zoster and Herpes Zoster Vaccine Rates Among Adults Living With and Without HIV in the Veterans Aging Cohort Study.

BACKGROUND: Despite historically high rates of herpes zoster among people living with HIV (PLWH), comparative studies of herpes zoster by HIV serostatus are lacking since the advent of combination antiretroviral therapy and availability of zoster vaccine. METHODS: Annual rates (2002-2015) of first-episode herpes zoster and zoster vaccination were calculated for PLWH and uninfected adults in the Veterans Aging Cohort Study and stratified by HIV serostatus and age. Herpes zoster was captured using ICD9 codes and vaccine receipt with procedural codes and pharmacy data. RESULTS: Of 45,177 PLWH and 103,040 uninfected veterans, rates of herpes zoster decreased among PLWH (17.6-8.1/1000) over the study period but remained higher than uninfected adults (4.1/1000) at the end of study period. Rates were higher in PLWH with lower CD4 (<200 vs >500 cells/µL: 18.0 vs 6.8/1000) and unsuppressed vs suppressed HIV-1 RNA (21.8 vs 7.1/1000). Restricted to virologically suppressed participants with CD4 >350 cells per microliter, herpes zoster rates were similar among PLWH aged younger than 60 years and aged 60 years and older in 2015 (6.6 vs 6.7/1000) but higher than all uninfected age groups. At study end, cumulative receipt of zoster vaccine for PLWH aged 60 years and older was less than half that of uninfected veterans: 98.7 vs 215.2/1000. CONCLUSIONS: Herpes zoster rates among PLWH have markedly decreased, but, even in cART-treated individuals, remain 50% higher than uninfected adults. Lower rates of zoster vaccine receipt combined with high rates of herpes zoster support the need for a safe and effective vaccine against herpes zoster for PLWH, formal zoster vaccine guidelines for PLWH, and consideration for expanded use at younger ages.

Abdominal obesity, sarcopenia, and osteoporosis are associated with frailty in men living with and without HIV.

OBJECTIVE: The relationships between frailty and body composition in older adults with HIV infection are poorly understood. We sought to describe associations between frailty and measures of body composition among adult men with HIV and without HIV. DESIGN/METHODS: Men with and without HIV (age 50-69 years) in the Multicenter AIDS Cohort Study (MACS) Bone Strength Substudy were included if evaluated for frailty (by Fried phenotype) and body composition [BMI, waist circumference, abdominal visceral (VAT) and subcutaneous (SAT) adipose tissue, sarcopenia, and osteopenia/osteoporosis]. All participants with HIV infection were on antiretroviral therapy. Multivariate multinomial logistic regression models were used to determine associations of frailty with body composition. RESULTS: A total of 399 men, including 199 men with HIV and 200 men without HIV, both with median age 60 years, constituted our study population. Frailty prevalence was 16% (men with HIV) vs. 8% (men without HIV). HIV serostatus was associated with a 2.43 times higher odds of frailty (P = 0.01). Higher waist circumference, VAT, sarcopenia, and femoral neck osteoporosis were associated with increased odds of frailty (aOR 4.18, 4.45, 4.15, and 13.6, respectively, and all P < 0.05); BMI and SAT were not. None of these measures presented a differential association with frailty by HIV serostatus (all P > 0.20). CONCLUSION: Higher abdominal obesity and sarcopenia were associated with frailty among men with and without HIV. Assessment of these body composition parameters may help detect frailty in the clinical setting.

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.

A Case of Fulminant Meningococcemia: It Is All in the Complement.

Eculizumab is a novel monoclonal antibody that inhibits complement-mediated hemolysis in patients with paroxysmal nocturnal hemoglobinuria (PNH). Complement deficiency is a well-known risk factor for meningococcal infection. We describe a case of a young patient with PNH treated with eculizumab who presented with a life-threatening case of nongroupable meningococcemia. As this new biologic agent becomes more widely prescribed, providers should be aware of the increased risk of meningococcemia. In addition to vaccination, providers may consider the use of oral penicillin for antibiotic prophylaxis against Neisseria meningitidis in these cases of functional complement deficiency.

Geriatric syndromes: new frontiers in HIV and sarcopenia.

: HIV infection, in many circumstances, can now be managed as a chronic disease due to the marked increase in life expectancy since the introduction of combination antiretroviral therapy (ART). As the patients who first had access to combination ART age into their 50s and 60s, the effects of chronic HIV infection on health have become an important research focus in HIV infection. People living with HIV appear to exhibit an earlier occurrence of some aging-related conditions compared to people without HIV, in part due to higher rates of comorbidities, high-risk behaviors (e.g. smoking, substance use), chronic immune activation, inflammation, and ART-specific factors. Some studies have even suggested an earlier-than-expected appearance of the 'geriatric syndromes,' which are complex medical syndromes of older adults that are associated with morbidity and mortality. The geriatric syndromes include a wide variety of disease processes ranging from incontinence and dementia to impairments in physical function. This review will focus on one geriatric syndrome, sarcopenia, in older HIV-infected populations, and its relation to other aging syndromes, including frailty and falls. The contribution of HIV itself, ART exposure, and specific comorbidities, and the importance of early recognition and prevention of these aging syndromes will be highlighted.

Resolution of Q Fever-Associated Cryoglobulinemia With Anti-CD20 Monoclonal Antibody Treatment.

Immunologic phenomena can complicate chronic infections with Coxiella burnetii (Q fever), including immune complex deposition causing vasculitis, neuropathy, and glomerulonephritis. We describe the case of a man with Q fever endocarditis, mixed cryoglobulinemia, and life-threatening vasculitis driven by immune complex deposition who was successfully treated with B cell depleting therapy (rituximab).

Representation of Latinos and Blacks in screening for and enrollment into preventive HIV vaccine trials in New York City.

INTRODUCTION: In the United States, Latinos and Blacks are disproportionately affected by HIV/AIDS, but have been underrepresented in HIV vaccine trials. We assessed screening and enrollment of Blacks and Latinos for preventive HIV vaccine trials conducted in New York City, 2009-2012. METHODS: A retrospective analysis was conducted among 18-50 year old men and transgender women screening for four preventive phase 1 and 2 HIV vaccine trials. Demographic, recruitment, and behavioral/medical eligibility data and outcome of screening were examined. To determine factors associated with enrollment, a multivariable logistic regression analysis was performed. RESULTS: Among 6077 individuals who provided contact information, 2536 completed a phone pre-screen. 96 (1.6% of recruitment contacts) enrolled. Latinos were 35.7% of recruitment contacts, but 17.7% of those enrolled, whereas Blacks were 22.5% and 32.3%, respectively. Among all Latinos, nearly one third were excluded for being uncircumcised, an eligibility criterion for several studies. In multivariable analysis among potentially eligible potential participants, controlling for age and recruitment method, Latinos were less likely than Whites to enroll in a preventive HIV vaccine trial (aOR 0.52, 95% CI 0.28-0.95) whereas Blacks were as likely as Whites (aOR 0.99, 95% CI 0.59-1.67). Individuals recruited through print advertisements, social media/internet, referral, and other modes were more likely to enroll compared to those recruited through in-person outreach, controlling for age and race/ethnicity. CONCLUSIONS: Targeted outreach has led to substantial inclusion of Latinos and Blacks, with Blacks comprising almost a third of those enrolled in these preventive HIV vaccine trials. Latinos, however, were less likely to enroll compared to Whites. Circumcision status as an eligibility criterion partly accounts for this, but further studies are warranted to address the reasons Latinos decide not to participate in preventive HIV vaccine trials.

HIV incidence among men diagnosed with early syphilis in Atlanta, San Francisco, and Los Angeles, 2004 to 2005.

BACKGROUND: Syphilis outbreaks among men who have sex with men (MSM) in the United States have raised concerns about increased HIV transmission in this population. We sought to estimate HIV incidence among men diagnosed with primary or secondary (P&S) syphilis in sexually transmitted disease (STD) clinics in Atlanta, San Francisco, and Los Angeles. METHODS: We analyzed deidentified sociodemographic information from routine syphilis surveillance databases and matching remnant sera from consecutive male patients with P&S syphilis who were tested for syphilis at 3 public health laboratories during January 2004 through January 2006. Deidentified sera positive for Treponema pallidum by particle agglutination were screened for HIV-1 antibodies by enzyme immunoassay (EIA). Specimens that were confirmed HIV-positive by Western blot analysis were then tested for recent HIV infection using the less sensitive (LS) HIV-1 Vironostika EIA and BED HIV-specific IgG/total IgG assay. RESULTS: Of 357 men with P&S syphilis (98 in Atlanta, 151 in San Francisco, and 108 in Los Angeles), 32% had primary syphilis and 85% were MSM (12% no MSM risk and 3% no information). The median age was 36 years; 40% were white, 31% black, 20% Hispanic, and 8% other. Among men with P&S syphilis, 160 (45%) were HIV-positive, of whom 8 were classified as having acquired recent HIV infection by the LS-Vironostika EIA (all confirmed by BED) and had no history of antiretroviral use or HIV-positive results >6 months earlier. Seven of the 8 men with recent HIV infection were MSM. The estimated HIV incidence was 9.5% per year (95% confidence interval [CI]: 2.9 to 16.0) among all men and 10.5% per year (95% CI: 2.7 to 18.3) among MSM. CONCLUSIONS: We found high HIV incidence among a high-risk population of US men diagnosed with P&S syphilis in STD clinics in Atlanta, San Francisco, and Los Angeles. Intensive integrated HIV/STD prevention programs are needed for this population.

Use of the serologic testing algorithm for recent HIV seroconversion (STARHS) to identify recently acquired HIV infections in men with early syphilis in Los Angeles County.

BACKGROUND: Syphilis outbreaks among men who have sex with men (MSM) in the United States, many of whom are HIV infected, have prompted increased concern for HIV transmission. METHODS: To identify whether men are acquiring HIV concomitantly or within the critical period of syphilis infection, banked Treponema pallidum particle agglutination-positive serum specimens from men with early syphilis infection were screened for HIV-1 antibody. Samples that were positive for HIV antibody were then tested with a less sensitive (LS) HIV-1 antibody enzyme immunoassay (serologic testing algorithm for recent HIV seroconversion [STARHS]) to identify HIV infections that occurred on average within the previous 6 months. RESULTS: Of the 212 specimens banked from men with early syphilis, 74 (35%) were HIV-positive. Of these, 15 tested non-reactive by the LS assay. Twelve of these 15 were considered to be recent infections by the LS assay and testing history. Eleven (92%) of the recent infections were among MSM. One man had primary syphilis, 6 (50%) had secondary syphilis, and 5 (42%) had early latent syphilis. Eight men (67%) reported sex with anonymous partners, and 3 (25%) reported consistent condom use. The estimated HIV incidence was 17% per year (95% confidence interval [CI]: 12%-22%) among all men with early syphilis, and it was 26% per year (95% CI: 91%-33%) among MSM. CONCLUSIONS: Syphilis epidemics in MSM may be contributing to HIV incidence in this population. The STARHS can be applied as a surveillance tool to assess HIV incidence in various at-risk populations, but further studies are necessary for validation.