Hyperimmune immunoglobulin for hospitalised patients with COVID-19 (ITAC): a double-blind, placebo-controlled, phase 3, randomised trial

BACKGROUND: Passive immunotherapy using hyperimmune intravenous immunoglobulin (hIVIG) to SARS-CoV-2, derived from recovered donors, is a potential rapidly available, specific therapy for an outbreak infection such as SARS-CoV-2. Findings from randomised clinical trials of hIVIG for the treatment of COVID-19 are limited. METHODS: In this international randomised, double-blind, placebo-controlled trial, hospitalised patients with COVID-19 who had been symptomatic for up to 12 days and did not have acute end-organ failure were randomly assigned (1:1) to receive either hIVIG or an equivalent volume of saline as placebo, in addition to remdesivir, when not contraindicated, and other standard clinical care. Randomisation was stratified by site pharmacy; schedules were prepared using a mass-weighted urn design. Infusions were prepared and masked by trial pharmacists; all other investigators, research staff, and trial participants were masked to group allocation. Follow-up was for 28 days. The primary outcome was measured at day 7 by a seven-category ordinal endpoint that considered pulmonary status and extrapulmonary complications and ranged from no limiting symptoms to death. Deaths and adverse events, including organ failure and serious infections, were used to define composite safety outcomes at days 7 and 28. Prespecified subgroup analyses were carried out for efficacy and safety outcomes by duration of symptoms, the presence of anti-spike neutralising antibodies, and other baseline factors. Analyses were done on a modified intention-to-treat (mITT) population, which included all randomly assigned participants who met eligibility criteria and received all or part of the assigned study product infusion. This study is registered with ClinicalTrials.gov, NCT04546581. FINDINGS: From Oct 8, 2020, to Feb 10, 2021, 593 participants (n=301 hIVIG, n=292 placebo) were enrolled at 63 sites in 11 countries; 579 patients were included in the mITT analysis. Compared with placebo, the hIVIG group did not have significantly greater odds of a more favourable outcome at day 7; the adjusted OR was 1·06 (95% CI 0·77–1·45; p=0·72). Infusions were well tolerated, although infusion reactions were more common in the hIVIG group (18·6% vs 9·5% for placebo; p=0·002). The percentage with the composite safety outcome at day 7 was similar for the hIVIG (24%) and placebo groups (25%; OR 0·98, 95% CI 0·66–1·46; p=0·91). The ORs for the day 7 ordinal outcome did not vary for subgroups considered, but there was evidence of heterogeneity of the treatment effect for the day 7 composite safety outcome: risk was greater for hIVIG compared with placebo for patients who were antibody positive (OR 2·21, 95% CI 1·14–4·29); for patients who were antibody negative, the OR was 0·51 (0·29–0·90; pinteraction=0·001). INTERPRETATION: When administered with standard of care including remdesivir, SARS-CoV-2 hIVIG did not demonstrate efficacy among patients hospitalised with COVID-19 without end-organ failure. The safety of hIVIG might vary by the presence of endogenous neutralising antibodies at entry. FUNDING: US National Institutes of Health

Infrequent detection of human papillomavirus infection in head and neck cancers in the Central African Republic: a retrospective study

Abstract We carried out a retrospective study on the prevalence of HPV and genotype distribution by nested PCR and nucleotide sequencing analysis, in formalin-fixed, paraffin-embedded biopsies of 135 head and neck cancers (HNC) and 29 cervical cancers received between 2009 and 2017 for diagnosis at the Laboratoire National de Biologie Clinique et de Santé Publique of Bangui, the capital city of the Central African Republic. One oropharyngeal squamous cell carcinoma sample was positive for HPV type 16. The overall HPV prevalence in HNC biopsies was 0.74% (95% CI: 0.0–2.2). Among the 29 cervical cancer samples, 19 (65.5%; 95% CI: 48.2–82.8) were positive for HPV. These results indicate that HNC are infrequently associated with HPV infection in the Central African Republic

Analytical Performances of Human Immunodeficiency Virus Type 1 RNA-Based Amplix® Real-Time PCR Platform for HIV-1 RNA Quantification

International audienc

High prevalence of cervical high-risk human papillomavirus infection mostly covered by Gardasil-9 prophylactic vaccine in adult women living in N'Djamena, Chad.

BackgroundWe conducted in 2018 a descriptive, quantitative, population-based, cross-sectional survey estimating the prevalence of cervical high-risk human papillomavirus (HR-HPV) infection and associated risk factors among adult women living in N'Djamena, Chad.MethodsFive of the 10 districts of N'Djamena were randomly selected for inclusion. Peer educators contacted adult women in community-churches or women association networks to participate in the survey and come to the clinic for women's sexual health "La Renaissance Plus", N'Djamena. Medical, socio-demographical and behavioral informations were collected. HPV DNA was detected and genotyped in endocervical swab using Anyplex II HPV28 genotyping test (Seegene, Seoul, South Korea).Results253 women (mean age, 35.0 years; range, 25-65) including 3.5% of HIV-positive women were prospectively enrolled. The prevalence of HPV infection was 22.9%, including 68.9% of HR-HPV infection and 27.6% being infected with multiple genotypes, providing a total HR-HPV prevalence of 15.8% (95% CI%: 11.3-20.3). The most prevalent HR-HPV genotypes were HPV-58, HPV-35, HPV-56, HPV-31, HPV-16, HPV-45, HPV-52 and HPV-18. HPV types targeted by the prophylactic Gardasil-9 vaccine were detected in nearly 70% (67.5%) and HPV-58 was the most frequently detected. HIV infection was a risk factor strongly associated with cervical infection with any HPV [adjusted Odds ratio (aOR): 17.4], multiple types of HPV (aOR: 8.9), HR-HPV (aOR: 13.2) and cervical infection with multiple HR-HPV (aOR: 8.4).ConclusionThese observations highlight the unsuspected high burden of cervical HR-HPV infection in Chadian women, and point the potential risk of further development of HPV-associated cervical precancerous and neoplastic lesions in a large proportion of women in Chad. The high rate of preventable Gardasil-9 vaccine genotypes constitutes the rationale for introducing primary vaccine prevention against cervical cancer in young female adolescents living in Chad

Unusual and unique distribution of anal high-risk human papillomavirus (HR-HPV) among men who have sex with men living in the Central African Republic.

BACKGROUND:High-risk (HR) human papillomavirus (HPV) infection remains a great concern in relation to African men who have sex with men (MSM), especially those infected with HIV. The prevalence of HR-HPV and associated risk factors was estimated in a cross-sectional observational study covering MSM living in Bangui, Central African Republic. METHODS:MSM receiving care at the Centre National de Référence des Infections Sexuellement Transmissibles et de la Thérapie Antirétrovirale, Bangui, were included. HIV serostatus and socio-demographic and behavioral characteristics were collected. HPV DNA was detected and genotyped on anal swabs using Anyplex™ II HPV28 test (Seegene, South Korea), and HSV DNA by in-house real-time PCR. Logistic regression analyses were used to determine risk factors associated with HPV outcomes. RESULTS:42 MSM (mean age, 23.2 years; range, 14-39) including 69.1% HIV-1-positive and 30.9% HIV-negative were prospectively enrolled. The prevalence of anal HPV was 69.1%, including 82.7% of HR-HPV which were multiple in 52.0%. The most prevalent genotypes were HPV-35, HPV-58, HPV-59 and HPV-31. While, HPV-16 and HPV-18 were present in a minority of samples. Multiple HR-HPV infection was more frequent in HIV-positive MSM (41.4%) with 2.7 genotypes per anal samples than in HIV-negative (7.7%) with 1.5 genotypes per anal samples. HPV types included in the prophylactic Gardasil-9® vaccine were detected in 68.9% of specimens and HPV-58 was the most frequently detected. MSM infected by HPV-16 and HPV-18 were all infected by HIV-1. Few anal swabs (11.9%) contained HSV-2 DNA without relationship with HPV detection. Condomless receptive anal intercourse was the main risk factor to being infected with any type of HPV and condomless insertive anal intercourse was significantly less associated with HPV contamination than receptive anal intercourse (Odd ratio = 0.02). CONCLUSION:MSM in Bangui are at-risk of HIV and HR-HPV anal infections. The unusual distribution of HPV-35 as predominant HPV suggests possible geographic specificities in the molecular epidemiology of HR-HPV in sub-Saharan Africa. Scaling up prevention strategies against HPV infection and related cancers adapted for MSM in Africa should be prioritized. Innovative interventions should be conceived for the MSM population living in Bangui

Distribution of anal HPV types according to the HIV-serostatus.

<p>Number of low-risk (LR) and high-risk (HR) HPV genotypes in 29 anal swab positive for HPV DNA by molecular biology according to HIV-serostatus among study men who have sex with men (n = 42) living in the Central African Republic.</p

Distribution of anal HPV types included (or not included) in the 9-valent Gardasil-9® vaccine.

<p>Number of low-risk (LR) and high-risk (HR) HPV genotypes in 29 anal swabs positive for HPV DNA by molecular biology according to their possible prevention by 9-valent HPV vaccine among study men who have sex with men (n = 42) living in the Central African Republic. Nota bene. The 9-valent Gardasil-9® vaccine (Merck & Co. Inc., New Jersey, USA) is effective against HPV genotypes 6, 11, 16, 18, 31, 33, 45, 52 and 58.</p

Univariate and multivariate logistic regression analyses for HPV-associated risk factors 42 study men who have sex with men (MSM) living in Bangui, Central African Republic.

<p>Univariate and multivariate logistic regression analyses for HPV-associated risk factors 42 study men who have sex with men (MSM) living in Bangui, Central African Republic.</p

Baseline characteristics according to sexual behavior and HIV serostatus among the 42 study men who have sex with men (MSM) living in Bangui, Central African Republic.

<p>Baseline characteristics according to sexual behavior and HIV serostatus among the 42 study men who have sex with men (MSM) living in Bangui, Central African Republic.</p