Brief Report: Surveillance of Congenital Anomalies After Exposure to Raltegravir or Elvitegravir During Pregnancy in the United Kingdom and Ireland, 2008–2018

BACKGROUND: The indisputable benefits of antiretroviral therapy (ART) in the reduction of mother-to-child-transmission of HIV (MTCT) have to be carefully balanced with the risks of embryo-foetal toxicities due to foetal exposure to maternal ART.The recent report of a potential safety signal with Dolutegravir use in pregnancy and potential increased rate of neural tube defects (NTDs), has raised the question of a potential class effect for Integrase Strand Inhibitors. To contribute real-world evidence we evaluated data on pregnant women receiving Raltegravir (RAL) or Elvitegravir (EVG) in the UK and Ireland. METHODS: The National Study of HIV in Pregnancy and Childhood (NSHPC) is a comprehensive population-based surveillance study collecting data on all HIV-positive pregnant women and their children. We collected data on all pregnancies exposed to an ART regimen containing RAL or EVG resulting in livebirth, stillbirth and induced abortion with an expected date of delivery between September 2008 and April 2018. Pregnancies were stratified into three groups of earliest exposure. RESULTS: A total of 908 pregnancies were exposed to a RAL or EVG-based regimen (875 to RAL and 33 to EVG). There were 886 live-born infants exposed to RAL, eight pregnancies ended in stillbirth and nine in induced abortions. Among the 886 live-born infants there were 23 (2.59% 95% CI 1.65, 3.86) reported congenital anomalies, two nervous system defects but no reported NTDs. Of the 33 pregnancies exposed to EVG, 31 resulted in live-born infants with no congenital anomaly and the remaining two pregnancies ended in induced abortion. CONCLUSIONS: The prevalence of congenital anomalies is consistent with national population estimates for 2008-2016 in the UK. More data are needed on safety of RAL and EVG in pregnancy

Pregnancy incidence and outcomes in women with perinatal HIV infection

OBJECTIVE(S): To estimate the incidence of first pregnancy in women living with perinatally-acquired HIV (PHIV) in the UK and to compare pregnancy management and outcomes with age-matched women with behaviourally-acquired HIV (BHIV). DESIGN: The National Study of HIV in Pregnancy and Childhood (NSHPC) is a comprehensive, population-based surveillance study that collects demographic and clinical data on all pregnant women living with HIV, their children, and all HIV-infected children in the UK & Ireland. METHODS: The incident rate ratio (IRR) of first pregnancy was calculated for all females of reproductive age who had been reported to the NSHPC as vertically infected children. These women and their pregnancies were compared to age-matched pregnant women with BHIV. RESULTS: Of the 630 females with PHIV reported in the UK as children, 7% (45) went on to have ≥1 pregnancy, with 70 pregnancies reported. The IRR of first pregnancy was 13 per 1000 woman-years. The BHIV comparison group comprised 118 women (184 pregnancies). Women with PHIV were more likely to be on cART at conception and have a lower baseline CD4 count (p < 0.01 for both). In adjusted analysis, PHIV and a low baseline CD4 count were risk factors for detectable viral load near delivery; older age at conception and being on cART at conception reduced this risk. CONCLUSIONS: Women with PHIV in the UK have a low pregnancy incidence, but those who become pregnant are at risk of detectable viral load near delivery, reflecting their often complex clinical history, adherence and drug resistance issues

Genomic characteristics and clinical effect of the emergent SARS-CoV-2 B.1.1.7 lineage in London, UK: a whole-genome sequencing and hospital-based cohort study

BACKGROUND: Emergence of variants with specific mutations in key epitopes in the spike protein of SARS-CoV-2 raises concerns pertinent to mass vaccination campaigns and use of monoclonal antibodies. We aimed to describe the emergence of the B.1.1.7 variant of concern (VOC), including virological characteristics and clinical severity in contemporaneous patients with and without the variant. METHODS: In this cohort study, samples positive for SARS-CoV-2 on PCR that were collected from Nov 9, 2020, for patients acutely admitted to one of two hospitals on or before Dec 20, 2020, in London, UK, were sequenced and analysed for the presence of VOC-defining mutations. We fitted Poisson regression models to investigate the association between B.1.1.7 infection and severe disease (defined as point 6 or higher on the WHO ordinal scale within 14 days of symptoms or positive test) and death within 28 days of a positive test and did supplementary genomic analyses in a cohort of chronically shedding patients and in a cohort of remdesivir-treated patients. Viral load was compared by proxy, using PCR cycle threshold values and sequencing read depths. FINDINGS: Of 496 patients with samples positive for SARS-CoV-2 on PCR and who met inclusion criteria, 341 had samples that could be sequenced. 198 (58%) of 341 had B.1.1.7 infection and 143 (42%) had non-B.1.1.7 infection. We found no evidence of an association between severe disease and death and lineage (B.1.1.7 vs non-B.1.1.7) in unadjusted analyses (prevalence ratio [PR] 0·97 [95% CI 0·72-1·31]), or in analyses adjusted for hospital, sex, age, comorbidities, and ethnicity (adjusted PR 1·02 [0·76-1·38]). We detected no B.1.1.7 VOC-defining mutations in 123 chronically shedding immunocompromised patients or in 32 remdesivir-treated patients. Viral load by proxy was higher in B.1.1.7 samples than in non-B.1.1.7 samples, as measured by cycle threshold value (mean 28·8 [SD 4·7] vs 32·0 [4·8]; p=0·0085) and genomic read depth (1280 [1004] vs 831 [682]; p=0·0011). INTERPRETATION: Emerging evidence exists of increased transmissibility of B.1.1.7, and we found increased virus load by proxy for B.1.1.7 in our data. We did not identify an association of the variant with severe disease in this hospitalised cohort. FUNDING: University College London Hospitals NHS Trust, University College London/University College London Hospitals NIHR Biomedical Research Centre, Engineering and Physical Sciences Research Council

Production properties of K*(892) vector mesons and their spin alignment as measured in the NOMAD experiment

First measurements of K*(892) mesons production properties and their spin alignment in nu_mu charged current (CC) and neutral current (NC) interactions are presented. The analysis of the full data sample of the NOMAD experiment is performed in different kinematic regions. For K*+ and K*- mesons produced in nu_mu CC interactions and decaying into K0 pi+/- we have found the following yields per event: (2.6 +/- 0.2 (stat.) +/- 0.2 (syst.))% and (1.6 +/- 0.1 (stat.) +/- 0.1 (syst.))% respectively, while for the K*+ and K*- mesons produced in nu NC interactions the corresponding yields per event are: (2.5 +/- 0.3 (stat.) +/- 0.3 (syst.))% and (1.0 +/- 0.3 (stat.) +/- 0.2 (syst.))%. The results obtained for the rho00 parameter, 0.40 +/- 0.06 (stat) +/- 0.03 (syst) and 0.28 +/- 0.07 (stat) +/- 0.03 (syst) for K*+ and K*- produced in nu_mu CC interactions, are compared to theoretical predictions tuned on LEP measurements in e+e- annihilation at the Z0 pole. For K*+ mesons produced in nu NC interactions the measured rho00 parameter is 0.66 +/- 0.10 (stat) +/- 0.05 (syst).Comment: 20 p

Search for nu(mu)-->nu(e) Oscillations in the NOMAD Experiment

We present the results of a search for nu(mu)-->nu(e) oscillations in the NOMAD experiment at CERN. The experiment looked for the appearance of nu(e) in a predominantly nu(mu) wide-band neutrino beam at the CERN SPS. No evidence for oscillations was found. The 90% confidence limits obtained are delta m^2 < 0.4 eV^2 for maximal mixing and sin^2(2theta) < 1.4x10^{-3} for large delta m^2. This result excludes the LSND allowed region of oscillation parameters with delta m^2 > 10 eV^2.Comment: 19 pages, 8 figures. Submitted to Phys. Lett.

A Study of Strange Particles Produced in Neutrino Neutral Current Interactions in the NOMAD Experiment

Results of a detailed study of strange particle production in neutrino neutral current interactions are presented using the data from the NOMAD experiment. Integral yields of neutral strange particles (K0s, Lambda, Lambda-bar) have been measured. Decays of resonances and heavy hyperons with an identified K0s or Lambda in the final state have been analyzed. Clear signals corresponding to K* and Sigma(1385) have been observed. First results on the measurements of the Lambda polarization in neutral current interactions have been obtained.Comment: Accepted for publication in Nuclear Physics B as a rapid communicatio

Search for the exotic Θ+\Theta^+ resonance in the NOMAD experiment

A search for exotic Theta baryon via Theta -> proton +Ks decay mode in the NOMAD muon neutrino DIS data is reported. The special background generation procedure was developed. The proton identification criteria are tuned to maximize the sensitivity to the Theta signal as a function of xF which allows to study the Theta production mechanism. We do not observe any evidence for the Theta state in the NOMAD data. We provide an upper limit on Theta production rate at 90% CL as 2.13 per 1000 of neutrino interactions.Comment: Accepted to European Physics Journal

A Precise Measurement of the Muon Neutrino-Nucleon Inclusive Charged Current Cross-Section off an Isoscalar Target in the Energy Range 2.5 < E_\nu < 40 GeV by NOMAD

We present a measurement of the muon neutrino-nucleon inclusive charged current cross-section, off an isoscalar target, in the neutrino energy range $2.5 \leq E_\nu \leq 40$ GeV. The significance of this measurement is its precision, $\pm 4$% in $2.5 \leq E_\nu \leq 10$ GeV, and $\pm 2.6$% in $10 \leq E_\nu \leq 40$ GeV regions, where significant uncertainties in previous experiments still exist, and its importance to the current and proposed long baseline neutrino oscillation experiments.Comment: 14 pages, 3 figures, submitted to Phys.Lett.

Final NOMAD results on nu_mu->nu_tau and nu_e->nu_tau oscillations including a new search for nu_tau appearance using hadronic tau decays

Results from the nu_tau appearance search in a neutrino beam using the full NOMAD data sample are reported. A new analysis unifies all the hadronic tau decays, significantly improving the overall sensitivity of the experiment to oscillations. The "blind analysis" of all topologies yields no evidence for an oscillation signal. In the two-family oscillation scenario, this sets a 90% C.L. allowed region in the sin^2(2theta)-Delta m^2 plane which includes sin^2(2theta)<3.3 x 10^{-4} at large Delta m^2 and Delta m^2 < 0.7 eV^2/c^4 at sin^2(2theta)=1. The corresponding contour in the nu_e->nu_tau oscillation hypothesis results in sin^2(2theta)<1.5 x 10^{-2} at large Delta m^2 and Delta m^2 < 5.9 eV^2/c^4 at sin^2(2theta)=1. We also derive limits on effective couplings of the tau lepton to nu_mu or nu_e.Comment: 46 pages, 16 figures, Latex, to appear on Nucl. Phys.