ABSTRACT Objectives The immunogenicity of hepatitis B vaccine is unsatisfactory in the people living with HIV (PLHIV). Studies evaluating optimal regimens to enhance immunogenicity have heretofore been inconclusive. The study was to compare the immunogenicity and safety of the four standard-dose and high-dose regimens of hepatitis B vaccine among PLHIV. Methods A randomized, parallel-controlled trial was conducted between May, 2020, and January, 2021. Patients were randomly assigned to receive 3 or 4 doses of 20 or 60 µg of hepatitis B vaccine. Seroconversion rate, high-level response rate, and geometric mean concentration (GMC) of antibody to hepatitis B surface antigen (anti-HBs) at weeks 12 and 28 were the main outcome measures. Results At week 28, the seroconversion rate and GMC of anti-HBs in both IM20 × 4 and IM60 × 4 groups were significantly higher than those in the IM20 × 3 group (P < 0.05), and the GMC of anti-HBs was numerically higher in the IM60 × 4 group than that in the IM20 × 4 group. Conclusions In PLHIV, both the four standard-dose and high-dose regimens significantly improved immunogenicity. The GMC of anti-HBs was numerically higher in the IM60 × 4 group than that in the IM20 × 4 group. Clinical trial registration ClinicalTrials.gov (NCT03962803)

Immunogenicity and safety of 4 intramuscular standard-dose and high-dose hepatitis B vaccine in people living with HIV: a randomized, parallel-controlled trial

Importance
Randomized clinical trials (RCTs) on COVID-19 are increasingly being posted as preprints before publication in a scientific, peer-reviewed journal.


Objective
To assess time to journal publication for COVID-19 RCT preprints and to compare differences between pairs of preprints and corresponding journal articles.


Evidence Review
This systematic review used a meta-epidemiologic approach to conduct a literature search using the World Health Organization COVID-19 database and Embase to identify preprints published between January 1 and December 31, 2021. This review included RCTs with human participants and research questions regarding the treatment or prevention of COVID-19. For each preprint, a literature search was done to locate the corresponding journal article. Two independent reviewers read the full text, extracted data, and assessed risk of bias using the Cochrane Risk of Bias 2 tool. Time to publication was analyzed using a Cox proportional hazards regression model. Differences between preprint and journal article pairs in terms of outcomes, analyses, results, or conclusions were described. Statistical analysis was performed on October 17, 2022.


Findings
This study included 152 preprints. As of October 1, 2022, 119 of 152 preprints (78.3%) had been published in journals. The median time to publication was 186 days (range, 17-407 days). In a multivariable model, larger sample size and low risk of bias were associated with journal publication. With a sample size of less than 200 as the reference, sample sizes of 201 to 1000 and greater than 1000 had hazard ratios (HRs) of 1.23 (95% CI, 0.80-1.91) and 2.19 (95% CI, 1.36-3.53) for publication, respectively. With high risk of bias as the reference, medium-risk articles with some concerns for bias had an HR of 1.77 (95% CI, 1.02-3.09); those with a low risk of bias had an HR of 3.01 (95% CI, 1.71-5.30). Of the 119 published preprints, there were differences in terms of outcomes, analyses, results, or conclusions in 65 studies (54.6%). The main conclusion in the preprint contradicted the conclusion in the journal article for 2 studies (1.7%).


Conclusions and Relevance
These findings suggest that there is a substantial time lag from preprint posting to journal publication. Preprints with smaller sample sizes and high risk of bias were less likely to be published. Finally, although differences in terms of outcomes, analyses, results, or conclusions were observed for preprint and journal article pairs in most studies, the main conclusion remained consistent for the majority of studies.

Comparison of Preprint Postings of Randomized Clinical Trials on COVID-19 and Corresponding Published Journal Articles: A Systematic Review.

Associated Factors and Immune Response to Hepatitis B Vaccine With Standard Schedule: A Prospective Study of HIV -Infected Adults in China

Hepatitis B (HB) vaccination is recommended for people with human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). We aimed to assess the immune response to the HB vaccine and associated factors using the standard vaccination schedule among people with HIV (PWH) in China. A prospective study was carried out from 2016 to 2020 in Beijing, China. PWH were given three 20 μg doses of recombinant HB vaccine at 0, 1, and 6 months. Blood samples were taken within 4–6 weeks after each dose to evaluate the anti-HBs levels. A total of 312 participants completed vaccination and serologic testing. The seroconversion (anti-HBs ≥ 10 IU/L) rates following the first, second, and third doses of the vaccine were 35.6% (95% CI: 30.3–40.9%), 55.1% (95% CI: 49.6–60.7%), and 86.5% (95% CI: 82.8–90.3%), respectively, and the geometric means of the anti-HBs titers were 0.8 IU/L (95% CI: 0.5–1.6 IU/L), 15.7 IU/L (95% CI: 9.4–26.3 IU/L), and 241.0 IU/L (95% CI: 170.3–341.1 IU/L), respectively. In multivariate analysis, after three doses of vaccination, age, CD4 cell count, and HIV-RNA viral load were significantly associated with strong, moderate, and weak response, respectively. These findings confirm that these personal health conditions are related to the HB response. HB vaccination in PWH using the standard schedule was still highly effective in the context of early treatment initiation, especially among participants aged 30 years and younger.

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Associated Factors and Immune Response to the Hepatitis B Vaccine with a Standard Schedule: A Prospective Study of People with HIV in China

Immunogenicity and persistence of high-dose recombinant hepatitis B vaccine in adults infected with human immunodeficiency virus in China: A randomized, double-blind, parallel controlled trial

Vaccination is urgently needed to prevent the global spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we conducted a randomized, parallel, controlled clinical trial for assessment of the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, aiming to determine an appropriate vaccination interval for high-risk occupational population. Participants were randomly assigned to receive two doses of inactivated SARS-CoV-2 vaccine (4 µg per dose) at an interval of either 14 days, 21 days or 28 days. The primary immunogenicity endpoints were neutralization antibody seroconversion and geometric mean titer (GMT) at 28 days after the second dose. Our results showed that the seroconversion rates (GMT ≥ 16) were all 100% in the three groups and the 0-21 and 0-28 groups elicited significantly higher SARS-CoV-2 neutralizing antibody level. All reported adverse reactions were mild. (Chinese Clinical Trial Registry: ChiCTR2100041705, ChiCTR2100041706)

/pdf/safety-and-immunogenicity-of-inactivated-sars-cov-2-vaccine-3bwvmas5fr.pdf

Yue Chang

Papers

Immunogenicity and persistence of high-dose recombinant hepatitis B vaccine in adults infected with human immunodeficiency virus in China: A randomized, double-blind, parallel controlled trial

Safety and Immunogenicity of Inactivated SARS-CoV-2 Vaccine in High-Risk Occupational Population: a randomized, parallel, controlled clinical trial