Abstract Background Meningococcal serogroup B (MenB) vaccine, 4CMenB, has been licensed in the United States (US) since 2015 for individuals aged 10–25 years. This study assessed 4CMenB in US infants when administered concomitantly with pneumococcal vaccine PCV13 and other routine infant vaccines (RIVs). Methods This phase 3b, observer-blind, placebo-controlled study (NCT03621670) randomized (2:1) healthy US infants to receive either 4CMenB administered concomitantly with PCV13 and other RIVs (N=786; 4CMenB+RIVs group) or placebo with PCV13 and other RIVs (N=409; Placebo+RIVs group) at 2, 4, 6, and 12 months of age. Primary objectives were to demonstrate the sufficiency of immune responses to MenB indicator strains (individually and combined), to demonstrate the non-inferiority of immune responses to PCV13 administered with 4CMenB+RIVs versus PCV13 plus placebo+RIVs, and assess safety. Immune responses to RIVs administered with 4CMenB+PCV13 versus RIVs plus placebo+PCV13 were investigated as secondary objectives. Results Pre-specified sufficiency criteria post-dose 3 and post-dose 4 were met for each MenB strain except NHBA and the composite response. Percentages of seroprotected participants (human serum bactericidal assay titers ≥lower limit of quantitation) against MenB indicator strains post-dose 4 were 86.1–99.6% in 4CMenB+RIVs group versus 0.0–2.8% in Placebo+RIVs group. The success criterion for achieving immunological non-inferiority of PCV13 was met, and concomitant 4CMenB administration did not adversely affect immune responses to other RIVs. 4CMenB co-administered with PCV13 and RIVs was generally well tolerated, with no safety concerns identified. Conclusions 4CMenB was well tolerated and immunogenic in US infants, producing no immunological interference when co-administered with other recommended vaccines.
ABSTRACT Background 40% of people with HIV (PWH) have metabolic dysfunction-associated steatotic liver disease (MASLD), but simple clinical tools for risk stratification do not exist. We evaluated whether adiposity indices are associated with MASLD in PWH and whether performance varies by race or ethnicity. Methods We examined PWH from a prospective, cross-sectional study conducted by the NIDDK-funded HIV NASH CRN. Participants had suppressed HIV-1 RNA and underwent vibration controlled transient elastography and anthropometric measurements. The primary outcome was MASLD, defined as controlled attenuation parameter (CAP) ≥263 dB/m with ≥1 cardiometabolic risk factor without heavy alcohol use or viral hepatitis. Adiposity indices included waist circumference (WC), body mass index (BMI), waist-to-height ratio (WHtR), body roundness index (BRI), relative fat mass (RFM), visceral adiposity index (VAI), and waist-to-hip ratio (WHR). Results Among 990 PWH, 445 (44.9%) had MASLD. All adiposity indices were strongly associated with MASLD (p<0.001). Several adiposity indices had good discrimination for MASLD in the overall cohort, including WC (AUC 0.79, 95% CI 0.76-0.81), WHtR (0.77 [0.74-0.80]), BRI (0.77 [0.74-0.80]), and BMI (0.75 [0.72-0.78]). WC, RFM, WHtR, and BRI had significant interactions with race (interaction p<0.05). Adiposity indices overall performed better in Black and Hispanic PWH compared to White PWH. Conclusions In PWH, adiposity indices were strongly associated with MASLD, though their discriminatory ability varied by race and ethnicity. Simple anthropometric indices may provide practical tools for MASLD risk assessment that could be tailored by race and ethnicity.
Abstract Background Bedaquiline resistance (BDQ-R) is increasing worldwide, but the contribution of primary BDQ-R remains unclear in countries with a high burden of RR-TB and widespread bedaquiline use. We aimed to estimate the prevalence of primary BDQ-R and to describe treatment outcomes amongst adults with primary BDQ-R in the Western Cape province, South Africa. Methods We conducted a retrospective cohort study of patients with BDQ-R identified through routine phenotypic bedaquiline susceptibility testing. Among patients with baseline BDQ-R (defined as resistance detected in those on no RR-TB treatment or with <1 month of treatment exposure), BDQ-R was categorised as primary (no prior bedaquiline exposure) or acquired (prior bedaquiline exposure). Drug resistance profiles, treatment outcomes, and time to culture conversion were analysed. Results Among 146 patients with baseline BDQ-R, 81 (55%) had primary BDQ-R. Resistance to other RR-TB drugs was common (except for linezolid). Of 80 patients with baseline BDQ-R and a treatment outcome, 28 (35%) died at a median of 276 days (IQR 129–459) after BDQ-R diagnosis. 117/136 (86%) achieved sputum culture conversion in a median of 97 days (IQR 89 –116). Acquired BDQ-R was associated with a lower hazard of culture conversion (adjusted HR: 0.37; p<0.001) and fewer favourable treatment outcomes (12.5% vs 47.9%; P=0.001) than primary BDQ-R. Conclusion Over half of BDQ-R cases were due to primary transmission. Outcomes were poor, but better in primary than acquired BDQ-R. Optimized susceptibility testing and treatment strategies are urgently needed to limit BDQ-R transmission.
Recent United States data on incidence, healthcare resource utilization (HRU), and costs for herpes zoster (HZ) in adults with human immunodeficiency virus (HIV) are lacking. This retrospective cohort study included insured adults during 2015–2022. HZ incidence rates were estimated among HZ-unvaccinated adults with HIV, HIV without other immunocompromising conditions (ICC) (HIV only), and 1,000,000 randomly selected adults with no ICC. Poisson regression was used to estimate adjusted incidence rate ratios (aIRRs) and 95% confidence intervals (CIs). All-cause HRU and costs were compared between propensity score-matched cohorts with HIV and HZ versus HIV without HZ during the first 1, 3, and 12 months after an episode of HZ. The incidence rates of HZ in the HIV (n = 53,700), HIV only (n = 41,544), and no ICC cohorts were 12.0, 10.3, and 5.6 per 1,000 person-years, respectively (HIV vs. no ICC: aIRR 2.05, 95% CI 1.92–2.19; HIV only vs. no ICC: aIRR 1.93, 95% CI 1.79–2.09). Mean all-cause per-patient costs were higher among adults with HIV and HZ during the first month (n = 1,078 and 4,312; cost difference $3,075, 95% CI $1,239–4,911) and the first 3 months (n = 994 and 3,976; $2,980, 95% CI $649–5,310) compared with adults with HIV without HZ. People with HIV are at increased risk of HZ compared to adults without ICC, and the costs associated with HZ among people with HIV are considerable. These findings support the importance of HZ prevention for adults with HIV.
Abstract Background Responses to Bacillus Calmette-Guérin (BCG) vaccination vary among adults, but the host genetic factors contributing to this variability remain unclear. Methods We conducted a prospective cohort study of 60 healthy adults without evidence of effective prior BCG immunization. All participants received BCG vaccination and were followed for 24 weeks. Based on their TST conversion status at 24 weeks after vaccination, participants were classified as immune converters (n = 28) or non-converters (n = 32). The TOLLIP rs5743854 polymorphism was genotyped, and genotype distributions were compared between the 2 groups. Results The distribution of TOLLIP rs5743854 genotypes differed significantly between immune converters and non-converters (Fisher’ s exact test, P = 0.008). C-allele-carrying genotypes (GC + CC) were more frequent among immune converters and were associated with a higher likelihood of immune conversion compared with the GG genotype (odds ratio, 4.71; 95% confidence interval, 1.51-14.76; P = 0.006). Conclusions TOLLIP rs5743854 genetic variation was associated with BCG-induced immune conversion in healthy adults. Our findings suggest that variation in TOLLIP may partly account for differences in individual responses to BCG vaccination and should be further evaluated in larger study populations.
