5 research outputs found
HIV testing algorithm.
<p>Approximately 800 women at each CRC were tested for HIV infection at screening as indicated. Those confirmed as seronegative and who met the entry criteria (299 at each CRC) were enrolled into the prospective cohort study and retested at 3, 6, 9, and 12 months after enrollment using the same algorithm. Participants who became HIV-positive while on study were referred to available sources of psychosocial and medical care and support. HIV-positive participants could continue on study for scheduled examinations per protocol with the exception of any further HIV testing and genital assessment, unless clinically indicated.</p
Pregnancy rates in the prospective cohort studies.
<p>Urine pregnancy tests were done at each study visit (screening, enrollment, and 3, 6, 9, and 12 months after enrollment in the cohort study). If test result was positive, the participant was to continue on study for follow-up per protocol. Estimated date of conception and estimated due date were to be recorded. If possible, follow-up was to continue for pregnancy outcome. Contraceptive counseling was provided and condoms were dispensed at each study visit.</p
Baseline Characteristics of Study Participants.
1<p>Two women were not eligible and excluded.</p>2<p>One woman was found to be less than 18 years of age after enrollment and was subsequently excluded.</p>3<p>One woman enrolled twice using a different name; data from her second enrollment were excluded.</p>4<p>Included disinfectants/soaps, cotton wool/wad of cloth, and traditional herbs (Mbekweni only).</p
HIV incidence in the prospective cohort studies.
<p>Women enrolled in the 12-month cohort studies visited the CRC at 3, 6, 9, and 12 months after enrollment for HIV testing according to the algorithm presented in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0021528#pone-0021528-g001" target="_blank">Figure 1</a>. HIV incidence rates were calculated based on a Poisson distribution with PY at risk in the denominator. They are expressed as number of cases per 100 PY, with 95% confidence intervals (CI). HIV infection was assumed to have occurred at the mid-point between the last available negative test and first positive test.</p
Efficacy, safety, and immunogenicity of a booster regimen of Ad26.COV2.S vaccine against COVID-19 (ENSEMBLE2) : results of a randomised, double-blind, placebo-controlled, phase 3 trial
Background Despite the availability of effective vaccines against COVID-19, booster vaccinations are needed to maintain vaccine-induced protection against variant strains and breakthrough infections. This study aimed to investigate the efficacy, safety, and immunogenicity of the Ad26.COV2.S vaccine (Janssen) as primary vaccination plus a booster dose.
Methods ENSEMBLE2 is a randomised, double-blind, placebo-controlled, phase 3 trial including crossover vaccination after emergency authorisation of COVID-19 vaccines. Adults aged at least 18 years without previous COVID-19 vaccination at public and private medical practices and hospitals in Belgium, Brazil, Colombia, France, Germany, the Philippines, South Africa, Spain, the UK, and the USA were randomly assigned 1:1 via a computer algorithm to receive intramuscularly administered Ad26.COV2.S as a primary dose plus a booster dose at 2 months or two placebo injections 2 months apart. The primary endpoint was vaccine efficacy against the first occurrence of molecularly confirmed moderate to severe-critical COVID-19 with onset at least 14 days after booster vaccination, which was assessed in participants who received two doses of vaccine or placebo, were negative for SARS-CoV-2 by PCR at baseline and on serology at baseline and day 71, had no major protocol deviations, and were at risk of COVID-19 (ie, had no PCR-positive result or discontinued the study before day 71). Safety was assessed in all participants; reactogenicity, in terms of solicited local and systemic adverse events, was assessed as a secondary endpoint in a safety subset (approximately 6000 randomly selected participants). The trial is registered with ClinicalTrials.gov, NCT04614948, and is ongoing.
Findings Enrolment began on Nov 16, 2020, and the primary analysis data cutoff was June 25, 2021. From 34 571 participants screened, the double-blind phase enrolled 31 300 participants, 14 492 of whom received two doses (7484 in the Ad26.COV2.S group and 7008 in the placebo group) and 11 639 of whom were eligible for inclusion in the assessment of the primary endpoint (6024 in the Ad26.COV2.S group and 5615 in the placebo group). The median (IQR) follow-up post-booster vaccination was 36 center dot 0 (15 center dot 0-62 center dot 0) days. Vaccine efficacy was 75 center dot 2% (adjusted 95% CI 54 center dot 6-87 center dot 3) against moderate to severe-critical COVID-19 (14 cases in the Ad26.COV2.S group and 52 cases in the placebo group). Most cases were due to the variants alpha (B.1.1.7) and mu (B.1.621); endpoints for the primary analysis accrued from Nov 16, 2020, to June 25, 2021, before the global dominance of delta (B.1.617.2) or omicron (B.1.1.529). The booster vaccine exhibited an acceptable safety profile. The overall frequencies of solicited local and systemic adverse events (evaluated in the safety subset, n=6067) were higher among vaccine recipients than placebo recipients after the primary and booster doses. The frequency of solicited adverse events in the Ad26.COV2.S group were similar following the primary and booster vaccinations (local adverse events, 1676 [55 center dot 6%] of 3015 vs 896 [57 center dot 5%] of 1559, respectively; systemic adverse events, 1764 [58 center dot 5%] of 3015 vs 821 [52 center dot 7%] of 1559, respectively). Solicited adverse events were transient and mostly grade 1-2 in severity.
Interpretation A homologous Ad26.COV2.S booster administered 2 months after primary single-dose vaccination in adults had an acceptable safety profile and was efficacious against moderate to severe-critical COVID-19. Studies assessing efficacy against newer variants and with longer follow-up are needed. Funding Janssen Research & Development.
Copyright (c) 2022 The Author(s). Published by Elsevier Ltd