Immunogenicity and safety of varying dosages of a fifth-wave influenza A/H7N9 inactivated vaccine given with and without AS03 adjuvant in healthy adults.

BACKGROUND: Human infections with the avian influenza A(H7N9) virus were first reported in China in 2013 and continued to occur in annual waves. In the 2016/2017 fifth wave, Yangtze River Delta (YRD) lineage viruses, which differed antigenically from those of earlier waves, predominated. METHODS: In this phase 2 double-blinded trial we randomized 720 adults ≥ 19 years of age to receive two injections of a YRD lineage inactivated A/Hong Kong/125/2017 fifth-wave H7N9 vaccine, given 21 days apart, at doses of 3.75, 7.5, and 15 µg of hemagglutinin (HA) with AS03A adjuvant and at doses of 15 and 45 µg of HA without adjuvant. RESULTS: Two doses of adjuvanted vaccine were required to induce HA inhibition (HI) antibody titers ≥ 40 in most participants. After two doses of the 15 µg H7N9 formulation, given with or without AS03 adjuvant, the proportion achieving a HI titer ≥ 40 against the vaccine strain at 21 days after the second vaccination was 65 % (95 % CI, 57 %-73 %) and 0 % (95 % CI, 0 %-4%), respectively. Among those who received two doses of the 15 µg adjuvanted formulation the proportion with HI titer ≥ 40 at 21 days after the second vaccination was 76 % (95 % CI, 66 %-84 %) in those 19-64 years of age and 49 % (95 % CI, 37 %-62 %) in those ≥ 65 years of age. Responses to the adjuvanted vaccine formulations did not vary by HA content. Antibody responses declined over time and responses against drifted H7N9 strains were diminished. Overall, the vaccines were well tolerated but, as expected, adjuvanted vaccines were associated with more frequent solicited systemic and local adverse events. CONCLUSIONS: AS03 adjuvant improved the immune responses to an inactivated fifth-wave H7N9 influenza vaccine, particularly in younger adults, but invoked lower responses to drifted H7N9 strains. These findings may inform future influenza pandemic preparedness strategies.

Factors Associated With Anal High-Grade Intraepithelial Lesions and Carcinoma Among Young Men Who Have Sex With Men and Transgender Women With HIV in Atlanta.

OBJECTIVE: This study aimed to evaluate factors associated with anal high-grade intraepithelial lesions (HSIL) and anal carcinoma among young men who have sex with men (MSM) and transgender women (TW) with HIV in Atlanta, GA, to better inform screening guidelines and preventative measures. MATERIALS AND METHODS: Cross-sectional retrospective chart review was completed for cisgender MSM and TW with HIV aged 13-25 years at the Grady Ponce and Family Youth Clinic in Atlanta, GA, from 2009 to 2020. High-grade anal disease was defined as anal intraepithelial neoplasia (AIN) 2, 3, or anal carcinoma (AIN 2+). Associations between clinical and demographic factors with AIN 2+ were estimated using logistic regression. Adjusted odds ratios (aORs) and associated 90% CIs are reported. RESULTS: One hundred nine MSM and TW with HIV who underwent anoscopy were included. One hundred three participants received anal biopsies, and 62% had AIN 2+. Being incompletely or unvaccinated against human papillomavirus (HPV, 0-2 doses) relative to being fully vaccinated (3 doses; aOR = 5.85; 90% CI = 1.28-26.83; p = .06) and having ever received surgical treatment for anogenital HPV (aOR = 2.89; 90% CI = 1.10-7.65; p = .07) were associated with AIN 2+, controlling for age and CD4 T-cell count at time of biopsy. CONCLUSIONS: Our study found a high prevalence of anal HSIL among young MSM and TW with HIV. Those who had ever received surgical treatment for anogenital HPV and those who were incompletely or unvaccinated against HPV were more likely to have HSIL. Our data emphasize the urgent need to improve HPV vaccination efforts and to pursue larger surveillance studies of anal HSIL and carcinoma among young MSM and TW with HIV.

"An Extra Variable to Consider"-Vaccine-Induced Seropositivity and Adolescent HIV Vaccine Clinical Trials.

Our study explores the understanding of vaccine-induced seropositivity (VISP) and its potential impact on US adolescents' and caregivers' willingness to participate in adolescent HIV vaccine clinical trials. Findings from in-depth interviews suggest that addressing concerns about VISP will be essential for future pediatric HIV vaccine trials in the United States.

Raltegravir-associated Drug-Reaction With Eosinophilia and Systemic Symptoms Syndrome in a Pediatric Patient Without Characteristic Human Leukocyte Antigen B*57:01 or B*53:01 alleles.

We present the first published case of raltegravir-associated drug-reaction with eosinophilia and systemic symptoms (DRESS) syndrome in a child without characteristic human leukocyte antigen haplotypes HLA-B*57:01 or HLA-B*53:01. A 4-year-old African American female with perinatally acquired human immunodeficiency virus infection was hospitalized for DRESS after starting a raltegravir-based antiretroviral regimen.

Innovations in HIV-1 Vaccine Design.

PURPOSE: The field of HIV-1 vaccinology has evolved during the last 30 years from the first viral vector HIV gene insert constructs to vaccination regimens using a myriad of strategies. These strategies now include germline-targeting, lineage-based, and structure-guided immunogen design. This narrative review outlines the historical context of HIV vaccinology and subsequently highlights the scientific discoveries during the last 6 years that promise to propel the field forward. METHODS: We conducted a search of 2 electronic databases, PubMed and EMBASE, for experimental studies that involved new HIV immunogen designs between 2013 and 2019. During the title and abstract reviews, publications were excluded if they were written in language other than English and/or were a letter to the editor, a commentary, or a conference-only presentation. We then used ClinicalTrials.gov to identify completed and ongoing clinical trials using these strategies. FINDINGS: The HIV vaccinology field has undergone periods of significant growth during the last 3 decades. Findings elucidated in preclinical studies have revealed the importance of the interaction between the cellular and humoral immune system. As a result, several new rationally designed vaccine strategies have been developed and explored in the last 6 years, including native-like envelope trimers, nanoparticle, and mRNA vaccine design strategies among others. Several of these strategies have shown enough promise in animal models to progress toward first-in-human Phase I clinical trials. IMPLICATIONS: Rapid developments in preclinical and early-phase clinical studies suggest that a tolerable and effective HIV vaccine may be on the horizon.

Performance of Interferon-Gamma Release Assays for Tuberculosis Screening in Pediatric Inflammatory Bowel Disease.

OBJECTIVES: The aim of the study was to analyze the diagnostic accuracy and utility of QuantiFERON-TB Gold In-Tube, an interferon-gamma release assay (IGRA), as a screening tool for latent tuberculosis infection (LTBI) in pediatric patients with inflammatory bowel disease (IBD) undergoing treatment with anti-tumor necrosis factor (anti-TNF) medications. To describe cases of tuberculosis in the pediatric IBD population, TB treatment courses, outcomes, and their effect on IBD management. METHODS: A single-center, retrospective cohort study of pediatric IBD patients who underwent tuberculosis screening. IGRA testing from 2011 to 2017 were analyzed to determine result rates, characteristics, and outcomes. RESULTS: One thousand seven hundred fifty-four (1,754) tests were performed on 859 patients. One thousand six hundred thirty-four (1,634) tests were negative, 9 were positive, and 111 were indeterminate. Eight of 9 positive tests resulted during repeat annual screening while receiving IBD treatment. Five patients were treated for latent tuberculosis infection (LTBI), and 4 were false-positives. IBD therapy was interrupted in 3 patients, with no negative long-term outcomes. We report 1 known false-negative, in a patient who developed disseminated TB on anti-TNF therapy. Indeterminate testing rates were higher at IBD diagnosis than during treatment (10.3% vs 5.3%, P < 0.001). Follow-up testing of indeterminate results was negative in all patients retested, with 14 patients lost to follow-up. No patient with indeterminate testing developed TB. CONCLUSIONS: IGRAs are a useful tool to screen for LTBI, both before anti-TNF therapy and during treatment. Results should be used in concert with detailed history and examination. Positive and indeterminate results should be promptly repeated for timely TB diagnosis and to minimize interruptions in IBD therapy.

Prevalence of Anal Squamous Intraepithelial Lesions in HIV-1-Infected Young Men Who Have Sex With Men and Transwomen.

OBJECTIVE: Anal cancer rates are increasing among HIV-infected persons. Although an efficacious human papillomavirus (HPV) vaccine is available, HPV vaccination rates remain low. Therefore, providers perform anal cancer screening, but there is no consensus on the optimal methods or timing of screening. This study was performed to determine the prevalence of and factors associated with anal squamous intraepithelial lesions in sexually active HIV-infected young men who have sex with men and transgender women. MATERIALS AND METHODS: We performed a single-center, retrospective study of sexually active HIV-infected young men who have sex with men and transgender women aged 13 to 24 years at an HIV clinic in Atlanta GA from 2009 to 2016. We used analysis of variance and χ tests of independence to evaluate bivariate associations and identify demographic, behavioral, and clinical risk factors. RESULTS: Of 314 subjects with a mean (SD) age of 20.4 (2.1) years at initial anal cytology testing, 5% had completed the HPV vaccine series at or before the time that cytology was obtained. Ninety-five percent of the anal cytology tests obtained were abnormal, and 72 (29%) of those subjects returned for diagnostic testing either by intraoperative biopsy or high-resolution anoscopy. Fifty-seven percent of those who underwent biopsy had histologic high-grade squamous intraepithelial lesions including 2 cases of carcinoma in situ. A history of greater than 20 lifetime sexual partners was associated with abnormal histology (probability < 0.001, p = .017). CONCLUSIONS: Our study highlights the value of early, standardized screening to avoid missing anal dysplasia or cancer, particularly in unvaccinated persons with high numbers of sexual partners.

Regular Marijuana Use is Associated with Poor Viral Suppression in HIV-Infected Adolescents and Young Adults.

There is a paucity of data regarding the impact of drug use on HIV suppression and care retention among adolescents and young adults (AYAs). We recruited a clinic-based sample of HIV infected AYAs to assess the prevalence of self-reported drug use. Clinical data, including retention and viral suppression, were abstracted from the electronic medical record. Logistic regression was used to evaluate marijuana and illicit drug use associations and to identify other risk factors. Of 200 participants (mean age 21, 2.4 years, 69% horizontally infected), 46% reported current drug use, with marijuana as the most commonly used drug. Any illicit drug use (aOR 1.99, 95% CI 1.06-3.73, p = 0.032) and lower education (aOR 2.11, 95% CI 1.09-4.08, p = 0.046) were associated with poor viral suppression in multivariable analyses. Considering marijuana use only, an association with poor viral suppression was more pronounced (aOR 2.10, 95% CI 1.12-3.94, p = 0.021). Drug use did not have a significant association with retention in care, but AYAs who were retained in HIV care were less likely to have poorly suppressed HIV (aOR 0.22, 95% CI 0.10-0.49, p < 0.001). High prevalence of marijuana use among HIV infected AYAs, and its association with poorly suppressed HIV, demonstrates the need for intervention strategies to decrease its consumption.

Gram-Positive Rods on a Cerebrospinal Fluid Gram Stain.

Cerebrospinal fluid (CSF) access device placement in the pediatric population presents challenges due to the development of infections following placement, access or revision, and/or shunt malfunctions. Here we report an unusual pediatric case of L. monocytogenes ventriculitis/VP shunt (VPS) infection and associated pseudocyst with an emphasis on the importance of VPS removal in clearing the infection due to biofilm formation.