An outbreak of HIV infections among people who inject drugs (PWID) started in 2014 in Luxembourg.
We conducted phylogenetic and epidemiological analyses among the PWID infected with HIV in Luxembourg ...or attending the supervised drug consumption facility (SDCF) to understand the main causes of the outbreak.
Between January 2013 and December 2017, analysis of medical files were performed from all PWID infected with HIV at the National Service of Infectious Diseases (NSID) providing clinical care nationwide. PWID were interviewed at NSID and SDCF using a standardized questionnaire focused on drug consumption and risk behaviours. The national drug monitoring system RELIS was consulted to determine the frequency of cocaine/heroin use. Transmission clusters were analysed by phylogenetic analyses using approximate maximum-likelihood. Univariate and multivariate logistic regression analyses were performed on epidemiological data collected at NSID and SDCF to determine risk factors associated with cocaine use.
From January 2013 to December 2017, 68 new diagnosis of HIV infection reported injecting drug use as the main risk of transmission at NSID. The proportion of female cases enrolled between 2013-2017 was higher than the proportion among cases enrolled prior to 2013. (33% vs 21%, p < 0.05). Fifty six viral sequences were obtained from the 68 PWID newly diagnosed for HIV. Two main transmission clusters were revealed: one HIV-1 subtype B cluster and one CRF14_BG cluster including 37 and 9 patients diagnosed since 2013, respectively. Interviews from 32/68 (47%) newly diagnosed PWID revealed that 12/32 (37.5%) were homeless and 27/32 (84.4%) injected cocaine. Increased cocaine injection was indeed reported by the RELIS participants from 53 to 63% in drug users with services contacts between 2012 and 2015, and from 5 to 22% in SDCF users between 2012 and 2016. Compared with PWID who injected only heroin (n = 63), PWID injecting cocaine and heroin (n = 107) were younger (mean of 38 vs 44 years, p≤0.001), reported more frequent piercing (≤0.001), shared and injected drugs more often (p≤0.01), and were more frequently HIV positive (p<0.05) at SDCF using univariate logistic regression analysis. Finally, in the multivariate analysis, use of heroin and cocaine was independently associated with younger age, piercing, sharing of drugs, and regular consumption (p<0.05).
Injecting cocaine is a new trend of drug use in Luxembourg associated with HIV infection in this recent outbreak among PWID.
Abstract
Background
The antiviral efficacy of remdesivir in COVID-19 hospitalized patients remains controversial.
Objectives
To estimate the effect of remdesivir in blocking viral replication.
...Methods
We analysed nasopharyngeal normalized viral loads from 665 hospitalized patients included in the DisCoVeRy trial (NCT 04315948; EudraCT 2020-000936-23), randomized to either standard of care (SoC) or SoC + remdesivir. We used a mathematical model to reconstruct viral kinetic profiles and estimate the antiviral efficacy of remdesivir in blocking viral replication. Additional analyses were conducted stratified on time of treatment initiation (≤7 or >7 days since symptom onset) or viral load at randomization (< or ≥3.5 log10 copies/104 cells).
Results
In our model, remdesivir reduced viral production by infected cells by 2-fold on average (95% CI: 1.5–3.2-fold). Model-based simulations predict that remdesivir reduced time to viral clearance by 0.7 days compared with SoC, with large inter-individual variabilities (IQR: 0.0–1.3 days). Remdesivir had a larger impact in patients with high viral load at randomization, reducing viral production by 5-fold on average (95% CI: 2.8–25-fold) and the median time to viral clearance by 2.4 days (IQR: 0.9–4.5 days).
Conclusions
Remdesivir halved viral production, leading to a median reduction of 0.7 days in the time to viral clearance compared with SoC. The efficacy was larger in patients with high viral load at randomization.
Weight gain is becoming increasingly prevalent amongst people with HIV (PWH) receiving contemporary antiretroviral treatment. We investigated BMI changes and clinical impact in a large prospective ...observational study.
PWH aged ≥18 years were included who started a new antiretroviral (baseline) during 2010-2019 with baseline and ≥1 follow-up BMI assessment available. Rates of clinical outcomes (cardiovascular disease CVD, malignancies, diabetes mellitus DM and all-cause mortality) were analysed using Poisson regression to assess effect of time-updated BMI changes (>1 kg/m 2 decrease, ±1 kg/m 2 stable, >1 kg/m 2 increase), lagged by 1-year to reduce reverse causality. Analyses were adjusted for baseline BMI plus key confounders including antiretroviral exposure.
6721 PWH were included; 72.3% were male, median age 48 years (interquartile range IQR 40-55). At baseline, 8.4% were antiretroviral-naive, and 5.0% were underweight, 59.7% healthy weight, 27.5% overweight, and 7.8% were living with obesity. There was an 8.2% increase in proportion of overweight and 4.8% in obesity over the study period (median follow-up 4.4 years IQR 2.6-6.7).100 CVDs, 149 malignancies, 144 DMs, and 257 deaths were observed with incidence rates 4.4, 6.8, 6.6, 10.6 per 1000 person-years of follow-up, respectively. Compared to stable BMI, >1 kg/m 2 increase was associated with increased risk of DM (adjusted incidence rate ratio IRR: 1.96, 95% confidence interval CI: 1.36-2.80) and >1 kg/m 2 decrease with increased risk of death (adjusted IRR: 2.33, 95% CI: 1.73-3.13). No significant associations were observed between BMI changes and CVD or malignancies.
A BMI increase was associated with DM and a decrease associated with death.
We describe four SARS-CoV-2 re-infections with a B.1.351 variant in 2021, in healthcare workers (HCWs) previously infected in 2020, before detection of this variant in Europe. Cases live in France, ...near the border with Luxembourg, where variants B.1.351 and B.1.1.7 circulated. All work in the same hospital unit where a cluster of COVID 19 with B1.351 variant occurred, affecting patients and HCWs. Before the cluster onset, HCWs used surgical masks, as per recommendations. After cluster onset, HCWs used FFP2 masks.
The role of antiviral treatment in coronavirus disease 2019 hospitalized patients is controversial. To address this question, we analyzed simultaneously nasopharyngeal viral load and the National ...Early Warning Score 2 (NEWS‐2) using an effect compartment model to relate viral dynamics and the evolution of clinical severity. The model is applied to 664 hospitalized patients included in the DisCoVeRy trial (NCT04315948; EudraCT 2020‐000936‐23) randomly assigned to either standard of care (SoC) or SoC + remdesivir. Then we use the model to simulate the impact of antiviral treatments on the time to clinical improvement, defined by a NEWS‐2 score lower than 3 (in patients with NEWS‐2 <7 at hospitalization) or 5 (in patients with NEWS‐2 ≥7 at hospitalization), distinguishing between patients with low or high viral load at hospitalization. The model can fit well the different observed patients trajectories, showing that clinical evolution is associated with viral dynamics, albeit with large interindividual variability. Remdesivir antiviral activity was 22% and 78% in patients with low or high viral loads, respectively, which is not sufficient to generate a meaningful effect on NEWS‐2. However, simulations predicted that antiviral activity greater than 99% could reduce by 2 days the time to clinical improvement in patients with high viral load, irrespective of the NEWS‐2 score at hospitalization, whereas no meaningful effect was predicted in patients with low viral loads. Our results demonstrate that time to clinical improvement is associated with time to viral clearance and that highly effective antiviral drugs could hasten clinical improvement in hospitalized patients with high viral loads.
AIM： To analyze the Hepatitis C virus （HCV） genotype distribution and transmission risk factors in a population of unselected patients in Luxembourg.
METHODS： Epidemiological information （gender, age ...and transmission risks） were collected from 802 patients newly diagnosed for hepatitis C and living in Luxembourg, among whom 228 patients referred from prison. Genotyping using 5＇noncoding （5＇NC） sequencing was performed. We compared categorical data using the Fisher＇s exact F-test and odds ratios （OR） were calculated for evaluating association of HCV genotype and risk factors.
RESULTS： The sex ratio was predominantly male （2.2） and individuals aged less than 40 years represented 49.6% of the population. Genotype 1 was predominant （53.4%） followed by genotype 3 （33%）. Among risk factors, intravenous drug usage （IVDU） was the most frequently reported （71.4%） followed by medical-related transmission （17.6%） including haemophilia, transfusion recipients and other nosocomial reasons. Genotype 3 was significantly associated to IVDU （OR = 4.84, P 〈 0.0001） whereas genotype 1 was significantly associated with a medical procedure （OR = 2.42, P 〈 0.001）. The HCV genotype distribution from inmate patients differed significantly from the rest of the population （Chi-square test with four degrees of freedom, P 〈 0.0001） with a higher frequency of genotype 3 （46.5% vs 27.5%） and a lower frequency of genotype 1 and 4 （44.7% vs 56.8% and 5.3% vs 9.6%, respectively）. IVDU was nearly exclusively reported as a risk factor in prison.
CONCLUSION： We report the first description of the HCV genotype distribution in Luxembourg. The repartition is similar to other European counties, with one of the highest European prevalence rates of genotype 3 （33%）. Since serology screening became available in 2992, IVDU remains the most common way of HCV transmission in Luxembourg.
The recent identification of neutralizing antibodies able to prevent viral rebound reemphasized the interest in humoral immune responses to control HIV-1 infection. In this study, we characterized ...HIV-1-inhibiting sequences from heavy-chain complementary determining region 3 (HCDR3) repertoires of a viremic controller.
IgM and IgG-derived HCDR3 repertoires of a viremic controller presenting plasma-neutralizing activity and characterized by over 20 years of infection with a stable CD4 T-cell count were displayed on filamentous phage to identify HCDR3 repertoire-derived peptides inhibiting HIV-1 entry.
Screening of phage libraries against recombinant gp120 led to the identification of an HCDR3-derived peptide sequence (LRTV-1) displaying antiviral properties against both X4 and R5 viruses. The interaction of LRTV-1 with gp120 was enhanced upon CD4 binding and sequence comparison revealed homology between LRTV-1 and the second extracellular loop of C-X-C chemokine receptor type 4 (CXCR4) (11/23) and the N-terminus of C-C chemokine receptor type 5 (CCR5) (7/23). Alanine scanning experiments identified different clusters of residues critical for interaction with the viral envelope protein.
LRTV-1 peptide is to date the smallest human HCDR3 repertoire-derived peptide identified by phage display inhibiting HIV entry of R5 and X4 viruses. This peptide recognizes a CD4-dependent gp120 epitope critical for coreceptor binding and mimics the surface of CXCR4 and CCR5. Our data emphasize the potential of human HCDR3 immune repertoires as sources of small biologically active peptides for HIV cure.
Direct comparisons between countries in core HIV care parameters are often hampered by differences in data collection.
Within the EuroSIDA study, we compared levels of antiretroviral treatment (ART) ...coverage and virological suppression (HIV RNA < 500 copies/mL) across Europe and explored temporal trends.
In three cross-sectional analyses in 2004-05, 2009-10 and 2014-15, we assessed country-specific percentages of ART coverage and virological suppression among those on ART. Temporal changes were analysed using logistic regression.
Overall, the percentage of people on ART increased from 2004-05 (67.8%) to 2014-15 (78.2%), as did the percentage among those on ART who were virologically suppressed (75.2% in 2004-05, 87.7% in 2014-15). However, the rate of improvement over time varied significantly between regions (p < 0.01). In 2014-15, six of 34 countries had both ART coverage and virological suppression of above 90% among those on ART. The pattern varied substantially across clinics within countries, with ART coverage ranging from 61.9% to 97.0% and virological suppression from 32.2% to 100%. Compared with Western Europe (as defined in this study), patients in other regions were less likely to be virologically suppressed in 2014-15, with the lowest odds of suppression (adjusted odds ratio = 0.16; 95% confidence interval (CI): 0.13-0.21) in Eastern Europe.
Despite overall improvements over a decade, we found persistent disparities in country-specific estimates of ART coverage and virological suppression. Underlying reasons for this variation warrant further analysis to identify a best practice and benchmark HIV care across EuroSIDA.
SARS-CoV-2 variants raise concern because of their high transmissibility and their ability to evade neutralizing antibodies elicited by prior infection or by vaccination. Here, we compared the ...neutralizing abilities of sera from 70 unvaccinated COVID-19 patients infected before the emergence of variants of concern (VOCs) and of 16 vaccine breakthrough infection (BTI) cases infected with Gamma or Delta against the ancestral B.1 strain, the Gamma, Delta and Omicron BA.1 VOCs using live virus. We further determined antibody levels against the Nucleocapsid (N) and full Spike proteins, the receptor-binding domain (RBD) and the N-terminal domain (NTD) of the Spike protein. Convalescent sera featured considerable variability in the neutralization of B.1 and in the cross-neutralization of different strains. Their neutralizing capacity moderately correlated with antibody levels against the Spike protein and the RBD. All but one convalescent serum failed to neutralize Omicron BA.1. Overall, convalescent sera from patients with moderate disease had higher antibody levels and displayed a higher neutralizing ability against all strains than patients with mild or severe forms of the disease. The sera from BTI cases fell into one of two categories: half the sera had a high neutralizing activity against the ancestral B.1 strain as well as against the infecting strain, while the other half had no or a very low neutralizing activity against all strains. Although antibody levels against the spike protein and the RBD were lower in BTI sera than in unvaccinated convalescent sera, most neutralizing sera also retained partial neutralizing activity against Omicron BA.1, suggestive of a better cross-neutralization and higher affinity of vaccine-elicited antibodies over virus-induced antibodies. Accordingly, the IC50: antibody level ratios were comparable for BTI and convalescent sera, but remained lower in the neutralizing convalescent sera from patients with moderate disease than in BTI sera. The neutralizing activity of BTI sera was strongly correlated with antibodies against the Spike protein and the RBD. Together, these findings highlight qualitative differences in antibody responses elicited by infection in vaccinated and unvaccinated individuals. They further indicate that breakthrough infection with a pre-Omicron variant boosts immunity and induces cross-neutralizing antibodies against different strains, including Omicron BA.1.
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