Safety and Immunogenicity of an mRNA-1273 Booster in Children.

BACKGROUND: A 2-dose mRNA-1273 primary series in children aged 6 months-5 years (25-µg) and 6-11 years (50-µg) had an acceptable safety profile and was immunogenic in the phase 2/3 KidCOVE study. We present data from KidCOVE participants who received an mRNA-1273 booster dose. METHODS: An mRNA-1273 booster dose (10-µg for children aged 6 months-5 years; 25-µg for children aged 6-11 years; age groups based on participant age at enrollment) was administered ≥6 months after primary series completion. The primary safety objective was the safety and reactogenicity of an mRNA-1273 booster dose. The primary immunogenicity objective was to infer efficacy of an mRNA-1273 booster dose by establishing noninferiority of neutralizing antibody (nAb) responses after a booster in children compared with nAb responses observed after the mRNA-1273 primary series in young adults (18-25 years) from the pivotal efficacy study. Data were collected from March 2022 to June 2023. RESULTS: Overall, 153 (6 months-5 years) and 2519 (6-11 years) participants received an mRNA-1273 booster dose (median age at receipt of booster: 2 and 10 years, respectively). The booster dose safety profile was generally consistent with that of the primary series in children; no new safety concerns were identified. An mRNA-1273 booster dose elicited robust nAb responses against ancestral SARS-CoV-2 among children and met prespecified noninferiority success criteria when compared with responses observed after the primary series in young adults. CONCLUSIONS: Safety and immunogenicity data support administration of a mRNA-1273 booster dose in children aged 6 months to 11 years. CLINICAL TRIALS REGISTRATION: NCT04796896.

Patient-Reported Outcomes Collection at an Urban HIV Clinic Associated With a Historically Black Medical College in the Southern United States: Qualitative Interview Study Among Patients With HIV.

BACKGROUND: Black Americans, particularly in the southern United States, are disproportionately affected by the US HIV epidemic. Patient-reported outcome (PRO) data collection can improve patient outcomes and provide oft-overlooked data on mental health, substance use, and patient adherence to antiretroviral therapy. OBJECTIVE: We piloted the use of an electronic tablet to collect PRO data on social and behavioral determinants of health among people with HIV at the Meharry Community Wellness Center, an HIV clinic affiliated with a Historically Black Medical College in Nashville, Tennessee. Our primary objective was to better understand patients' experiences and comfort with using an electronic PRO tool through patient interviews. METHODS: We enrolled 100 people with HIV in care at the Meharry Community Wellness Center consecutively to completely validate PRO tools using the Research Electronic Data Capture platform on a hand-held tablet. Using a purposive sampling strategy, we enrolled 20 of the 100 participants in an in-depth interview (IDI). Interview guide development was grounded in the cognitive-behavioral model, in which thoughts, feelings, and behaviors are interrelated. IDIs were audio recorded, transcribed, deidentified, and formatted for coding. A hierarchical coding system was developed and refined using an inductive-deductive approach. RESULTS: Among the 100 people with HIV enrolled, the median age was 50 (IQR 42-54) years; 89% (n=89) were Black, 60% (n=60) were male, and 82% (n=82) were living below 100% of the federal poverty level in 2016. Five major interview themes emerged: overall experience, question content, sensitive topics, clinic visit impact, and future recommendations. IDI participants felt that the tablet was easy to use and that the question content was meaningful. Question content related to trauma, sexual and drug use behaviors, mental health, stigma, and discrimination elicited uncomfortable or distressing feelings in some participants. Patients expressed a strong desire to be truthful, and most would complete these surveys without compensation at future visits if offered. CONCLUSIONS: The use of an electronic tablet to complete PRO data collection was well received by this cohort of vulnerable persons in HIV care in the southern United States. Despite some discomfort related to question content, our cohort overwhelmingly believed this was a meaningful part of their medical experience and expressed a high desire for truthfulness. Future research will focus on scaling up the implementation and evaluation of PRO data collection in a contextually appropriate manner while obtaining input from providers and staff to ensure that the collected data are both applicable and actionable.

Evaluation of mRNA-1273 Vaccine in Children 6 Months to 5 Years of Age.

BACKGROUND: The safety, reactogenicity, immunogenicity, and efficacy of the mRNA-1273 coronavirus disease 2019 (Covid-19) vaccine in young children are unknown. METHODS: Part 1 of this ongoing phase 2-3 trial was open label for dose selection; part 2 was an observer-blinded, placebo-controlled evaluation of the selected dose. In part 2, we randomly assigned young children (6 months to 5 years of age) in a 3:1 ratio to receive two 25-µg injections of mRNA-1273 or placebo, administered 28 days apart. The primary objectives were to evaluate the safety and reactogenicity of the vaccine and to determine whether the immune response in these children was noninferior to that in young adults (18 to 25 years of age) in a related phase 3 trial. Secondary objectives were to determine the incidences of Covid-19 and severe acute respiratory syndrome coronavirus 2 infection after administration of mRNA-1273 or placebo. RESULTS: On the basis of safety and immunogenicity results in part 1 of the trial, the 25-µg dose was evaluated in part 2. In part 2, 3040 children 2 to 5 years of age and 1762 children 6 to 23 months of age were randomly assigned to receive two 25-µg injections of mRNA-1273; 1008 children 2 to 5 years of age and 593 children 6 to 23 months of age were randomly assigned to receive placebo. The median duration of follow-up after the second injection was 71 days in the 2-to-5-year-old cohort and 68 days in the 6-to-23-month-old cohort. Adverse events were mainly low-grade and transient, and no new safety concerns were identified. At day 57, neutralizing antibody geometric mean concentrations were 1410 (95% confidence interval [CI], 1272 to 1563) among 2-to-5-year-olds and 1781 (95% CI, 1616 to 1962) among 6-to-23-month-olds, as compared with 1391 (95% CI, 1263 to 1531) among young adults, who had received 100-µg injections of mRNA-1273, findings that met the noninferiority criteria for immune responses for both age cohorts. The estimated vaccine efficacy against Covid-19 was 36.8% (95% CI, 12.5 to 54.0) among 2-to-5-year-olds and 50.6% (95% CI, 21.4 to 68.6) among 6-to-23-month-olds, at a time when B.1.1.529 (omicron) was the predominant circulating variant. CONCLUSIONS: Two 25-µg doses of the mRNA-1273 vaccine were found to be safe in children 6 months to 5 years of age and elicited immune responses that were noninferior to those in young adults. (Funded by the Biomedical Advanced Research and Development Authority and National Institute of Allergy and Infectious Diseases; KidCOVE ClinicalTrials.gov number, NCT04796896.).

Evaluation of mRNA-1273 Covid-19 Vaccine in Children 6 to 11 Years of Age.

BACKGROUND: Vaccination of children to prevent coronavirus disease 2019 (Covid-19) is an urgent public health need. The safety, immunogenicity, and efficacy of the mRNA-1273 vaccine in children 6 to 11 years of age are unknown. METHODS: Part 1 of this ongoing phase 2-3 trial was open label for dose selection; part 2 was an observer-blinded, placebo-controlled expansion evaluation of the selected dose. In part 2, we randomly assigned children (6 to 11 years of age) in a 3:1 ratio to receive two injections of mRNA-1273 (50 µg each) or placebo, administered 28 days apart. The primary objectives were evaluation of the safety of the vaccine in children and the noninferiority of the immune response in these children to that in young adults (18 to 25 years of age) in a related phase 3 trial. Secondary objectives included determination of the incidences of confirmed Covid-19 and severe acute respiratory syndrome coronavirus 2 infection, regardless of symptoms. Interim analysis results are reported. RESULTS: In part 1 of the trial, 751 children received 50-µg or 100-µg injections of the mRNA-1273 vaccine, and on the basis of safety and immunogenicity results, the 50-µg dose level was selected for part 2. In part 2 of the trial, 4016 children were randomly assigned to receive two injections of mRNA-1273 (50 µg each) or placebo and were followed for a median of 82 days (interquartile range, 14 to 94) after the first injection. This dose level was associated with mainly low-grade, transient adverse events, most commonly injection-site pain, headache, and fatigue. No vaccine-related serious adverse events, multisystem inflammatory syndrome in children, myocarditis, or pericarditis were reported as of the data-cutoff date. One month after the second injection (day 57), the neutralizing antibody titer in children who received mRNA-1273 at a 50-µg level was 1610 (95% confidence interval [CI], 1457 to 1780), as compared with 1300 (95% CI, 1171 to 1443) at the 100-µg level in young adults, with serologic responses in at least 99.0% of the participants in both age groups, findings that met the prespecified noninferiority success criterion. Estimated vaccine efficacy was 88.0% (95% CI, 70.0 to 95.8) against Covid-19 occurring 14 days or more after the first injection, at a time when B.1.617.2 (delta) was the dominant circulating variant. CONCLUSIONS: Two 50-µg doses of the mRNA-1273 vaccine were found to be safe and effective in inducing immune responses and preventing Covid-19 in children 6 to 11 years of age; these responses were noninferior to those in young adults. (Funded by the Biomedical Advanced Research and Development Authority and the National Institute of Allergy and Infectious Diseases; KidCOVE ClinicalTrials.gov number, NCT04796896.).

The effect of homelessness on viral suppression in an underserved metropolitan area of middle Tennessee: potential implications for ending the HIV epidemic.

BACKGROUND: A wealth of scientific evidence supports the effectiveness of HIV prophylaxis and treatment. Homelessness is strongly associated with the health status and viral suppression among underserved populations and can undermine the national plan to eliminate HIV by 2030. This retrospective observational study examined the extent in which homelessness affects HIV treatment in an underserved urban area of Middle Tennessee in 2014-2019. RESULTS: Among 692 HIV-seropositive patients, the proportion of homeless patients increased from 13.5% in 2014 to 27.7% in 2019, thrice the national average for HIV-seropositive people (8.4%) and twice that of HIV positive patients who are participating in Ryan White programs nationwide (12.9%). Our findings suggest that homeless patients were half as likely to achieve viral suppression as compared to those who had a permanent/stable home [OR 0.48 (0.32-0.72), p-value < 0.001]. CONCLUSION: Our study indicates that homelessness may play an important role in viral suppression among persons living with HIV/AIDS in Middle Tennessee.

Outcomes from the Adaptation of an Evidence-Based Peer Linkage & Re-Engagement Intervention for Women of Color with HIV in Three Urban Clinics.

Peer interventions have demonstrated efficacy with improving HIV health outcomes. Yet, little is known about factors associated with their uptake into the clinic setting. Three urban sites in the US were funded to adapt, implement and evaluate a peer intervention to improve HIV health outcomes for 173 out of care and newly diagnosed women of color. Peers worked with cis and transgender women of color for four months to achieve the goals of linkage and retention in HIV case management and medical care. Results were 96% of women were linked to medical care, 73% were retained in care and 81% were virally suppressed post 12 months. The average duration of the peer intervention was seven months. Women who received four peer encounters had a 10% increase in retention in care and viral suppression. The findings highlight key elements such as dose and duration of client interaction for peer staff as part of the health care team.

Addressing and Inspiring Vaccine Confidence in Black, Indigenous, and People of Color During the Coronavirus Disease 2019 Pandemic.

During the coronavirus disease 2019 (COVID-19) pandemic, we have witnessed profound health inequities suffered by Black, Indigenous, and People of Color (BIPOC). These manifested as differential access to testing early in the pandemic, rates of severe disease and death 2-3 times higher than white Americans, and, now, significantly lower vaccine uptake compared with their share of the population affected by COVID-19. This article explores the impact of these COVID-19 inequities (and the underlying cause, structural racism) on vaccine acceptance in BIPOC populations, ways to establish trustworthiness of healthcare institutions, increase vaccine access for BIPOC communities, and inspire confidence in COVID-19 vaccines.

The Effects of Perceived Stress and Cortisol Concentration on Antiretroviral Adherence When Mediated by Psychological Flexibility Among Southern Black Men Living with HIV.

This pilot study investigates the correlation between psychological stress and antiretroviral therapy (ART) adherence and plasma HIV RNA (viral load) as mediated by psychological flexibility among Black men in the south. Data were collected from 48 HIV-positive, low income Black men. Results indicate a strong positive correlation between perceived stress and psychological inflexibility (adjusted for age and income rs = 0.67; p < 0.001), a negative correlation between psychological inflexibility and ART adherence (adjusted rs = - 0.32; p = 0.03), a negative correlation between perceived stress and ART adherence (adjusted rs = - 0.45; p = 0.006), and a negative correlation between ART adherence and viral load (adjusted rs = - 0.37; p = 0.04). Our findings suggest stress decreases adherence to ART and viral suppression among Black men living with HIV. However, psychological flexibility did not mediate the relationship between stress and treatment adherence. Hair cortisol concentrations were high (mean of 34.2 pg/mg), but uncorrelated with adherence.

A Piece of History: The Legacy of George W. Counts and Underrepresented Populations.

The fight for social justice and diversity in medicine stems from racial inequalities and discrimination that have permeated our society for centuries. As America has become more diverse in recent years, African American physicians remain largely underrepresented in the healthcare workforce and academic medicine. In the field of infectious diseases, one man, George W. Counts, has shouldered the struggle to end disparities in education, training, research, and academic advancement. This article celebrates his legacy and rekindles the discussion about inclusion, diversity, access, and equity in infectious diseases.

Location Matters: Geographic Disparities and Impact of Coronavirus Disease 2019.

The coronavirus disease 2019 (COVID-19) pandemic in the United States has revealed major disparities in the access to testing and messaging about the pandemic based on the geographic location of individuals, particularly in communities of color, rural areas, and areas of low income. This geographic disparity, in addition to deeply rooted structural inequities, have posed additional challenges to adequately diagnose and provide care for individuals of all ages living in these settings. We describe the impact that COVID-19 has had on geographically disparate populations in the United States and share our recommendations on what might be done to ameliorate the current situation.

Hepatitis C Coinfection and Mortality in People Living with HIV in Middle Tennessee.

HIV and hepatitis C virus (HCV) coinfection is associated with poor health outcomes. This study was designed to assess risk factors for and mortality with coinfection before direct-acting antiviral treatment availability in a state with an evolving opioid epidemic. HCV infection was determined from review of the medical record at two clinics serving the majority of people living with HIV (PLWH) in care in Middle Tennessee from 2004 to 2013. Association of potential risk factors with HCV-positivity was assessed using logistic regression. Association of HCV-positivity with mortality was assessed with a Cox proportional hazards model, adjusting for selected covariates. A total of 3,501 patients were included: 24% female; 51% men who have sex with men; 47% white; 44% African American/black; median age of 38 at their first visit; median most recent CD4 count 502 cells/µL (301-716); and HIV viral load 47 copies/mL (39-605); followed for a median of 3.0 (1-5) years. Prevalence of HCV was 13%. Those with a history of injection drug use (IDU) demonstrated the highest odds of HCV-positivity [odds ratio 12.94; 95% confidence interval (CI) 9.39-17.83]. There were 305 deaths; median age at death was 47 years (40-53). HCV coinfection was associated with greater mortality (hazard ratio 1.61; 95% CI 1.20-2.17; p < .001). Among PLWH, HCV coinfection was associated with IDU and an independent predictor of mortality. These results affirm the importance of HCV coinfection and inform interventions targeting the continuum of HCV care, uptake of HCV treatment, and the impact of drug use in this population.

Higher Prevalence of Human Papillomavirus-Related Cervical Precancerous Abnormalities in HIV-Infected Compared to HIV-Uninfected Women.

INTRODUCTION: Persistent high risk human papillomavirus (hrHPV) has been associated with cervical abnormalities and cancer. There are few studies comparing HIV-infected with uninfected African American women from the Southern U.S. We evaluated medical records of a women's cohort in an urban clinic in Tennessee to assess the prevalence of hrHPV and cytology correlates, as well as HPV vaccination rates. METHODS: We reviewed medical records of 50 HIV infected and 304 HIV uninfected women, including Pap smears and hrHPV. RESULTS: HIV-infected women were older than HIV-uninfected women (p<0.0001) and were more likely to have hrHPV (p=<0.0001) and LGSIL/HGSIL (p=0.006). Within the HIV uninfected group, Hispanic women were younger than non-Hispanic African American women (p=0.04) and non-Hispanic white women (p=0.0002). Non-Hispanic African-American women were younger (p=0.004) than non-Hispanic white women. Both HIV-uninfected and HIV-infected women had an 11-fold and 5-fold odds, respectively, of having precancerous lesions when harboring hrHPV, compared to hrHPV-uninfected women. Of the 125 HIV-uninfected women, only 17% had received at least one dose of the HPV vaccine. None of the 21 vaccine recipients had evidence of SILs compared to 9% of vaccine non-recipients (p=0.35, Fisher's exact test). CONCLUSION: HIV-infected women remained at significantly higher risk for developing cervical precancerous lesions when exposed to hrHPV than their uninfected counterparts. Hispanic women were least likely to have been vaccinated. Missed HPV vaccination trended towards being associated with a higher odds of precancerous lesions. Routine HPV vaccination should be reinforced for adolescents and young women using public hospital facilities of all races and ethnic backgrounds.

Immunity to measles in pregnant mothers and in cord blood of their infants: impact of HIV status and mother's place of birth.

Antibody levels to measles were evaluated in 16 HIV-seropositive and 34 seronegative pregnant women and in cord blood samples of their infants. Infants were followed prospectively, and a second blood sample was taken at 3-7 months of age. Antibody levels were significantly lower in HIV-seropositive pregnant women and HIV-exposed cord bloods at birth (p=0.01 and 0.04, respectively) compared to controls. The prevalence of protective immunity (> or =1.09 optical density ratio) was also significantly lower (p=0.02) in HIV-seropositive pregnant women. T-cell counts were lower in HIV-seropositive women who were nonimmune (268/mm3) to measles compared to those who were immune (618/mm3), but the difference did not reach significance (p=0.07). Immunity to measles declined significantly to nonprotective levels in all infant samples obtained at 3-7 months of age. A secondary analysis determined the impact of mother's place of birth. Antibody levels were significantly higher (p=0.03) in foreign-born HIV-seronegative pregnant women and cord blood samples (p=0.01) compared to U.S.-born HIV-seronegative pregnant women seen in our inner-city clinic. Thus, HIV-seropositive and even some seronegative U.S.-born women may need a booster vaccine to ensure passage of adequate levels of passive immunity.

Meningitis caused by Salmonella panama in infants.

Salmonella panama is group-D nontyphi salmonella strongly associated with invasive infection, including meningitis. So far, no case of S. panama meningitis has been reported from the United States, and none has ever been reported in babies >3.5 months of age. To the best of our knowledge, we are reporting the first such case in English-language literature.