Emergence and evolution of TP53 mutations are a key feature of disease progression in myelodysplastic patients with lower-risk del(5q) treated with lenalidomide.

International audienceno abstrac

Myocardial Infarction incidence during national lockdown in two French provinces unevenly affected by COVID-19 outbreak: An observational study

International audienceBackground: A reduction of admission for MI has been reported in most countries affected by COVID-19. No clear explanation has been provided.Methods: To report the incidence of myocardial infarction (MI) admission during COVID-19 pandemic and in particular during national lockdown in two unequally affected French provinces (10-million inhabitants) with a different media strategy, and to describe the magnitude of MI incidence changes relative to the incidence of COVID-19-related deaths. A longitudinal study to collect all MIs from January 1 until May 17, 2020 (study period) and from the identical time period in 2019 (control period) was conducted in all centers with PCI-facilities in northern "Hauts-de-France" province and western "Pays-de-la-Loire" Province. The incidence of COVID-19 fatalities was also collected.Findings: In "Hauts-de-France", during lockdown (March 18-May 10), 1500 COVID-19-related deaths were observed. A 23% decrease in MI-IR (IRR=0.77;95%CI:0.71-0.84, p<0.001) was observed for a loss of 272 MIs (95%CI:-363,-181), representing 18% of COVID-19-related deaths. In "Pays-de-la-Loire", 382 COVID-19-related deaths were observed. A 19% decrease in MI-IR (IRR=0.81; 95%CI=0.73-0.90, p<0.001) was observed for a loss of 138 MIs (95%CI:-210,-66), representing 36% of COVID-19-related deaths. While in "Hauts-de-France" the MI decline started before lockdown and recovered 3 weeks before its end, in "Pays-de-la-Loire", it started after lockdown and recovered only by its end. In-hospital mortality of MI patients was increased during lockdown in both provinces (5.0% vs 3.4%, p=0.02).Interpretation: It highlights one of the potential collateral damages of COVID-19 outbreak on cardiovascular health with a dramatic reduction of MI incidence. It advocates for a careful and weighted communication strategy in pandemic crises.Funding: The study was conducted without external funding

Rilpivirine in HIV-1-positive women initiating pregnancy: to switch or not to switch?

International audienceBackgroundSafety data about rilpivirine use during pregnancy remain scarce, and rilpivirine plasma concentrations are reduced during second/third trimesters, with a potential risk of viral breakthroughs. Thus, French guidelines recommend switching to rilpivirine-free combinations (RFCs) during pregnancy.ObjectivesTo describe the characteristics of women initiating pregnancy while on rilpivirine and to compare the outcomes for virologically suppressed subjects continuing rilpivirine until delivery versus switching to an RFC.MethodsIn the ANRS-EPF French Perinatal cohort, we included women on rilpivirine at conception in 2010–18. Pregnancy outcomes were compared between patients continuing versus interrupting rilpivirine. In women with documented viral suppression (<50 copies/mL) before 14 weeks of gestation (WG) while on rilpivirine, we compared the probability of viral rebound (≥50 copies/mL) during pregnancy between subjects continuing rilpivirine versus those switching to RFC.ResultsAmong 247 women included, 88.7% had viral suppression at the beginning of pregnancy. Overall, 184 women (74.5%) switched to an RFC (mostly PI/ritonavir-based regimens) at a median gestational age of 8.0 WG. Plasma HIV-1 RNA nearest delivery was <50 copies/mL in 95.6% of women. Among 69 women with documented viral suppression before 14 WG, the risk of viral rebound was higher when switching to RFCs than when continuing rilpivirine (20.0% versus 0.0%, P = 0.046). Delivery outcomes were similar between groups (overall birth defects, 3.8/100 live births; pregnancy losses, 2.0%; preterm deliveries, 10.6%). No HIV transmission occurred.ConclusionsIn virologically suppressed women initiating pregnancy, continuing rilpivirine was associated with better virological outcome than changing regimen. We did not observe a higher risk of adverse pregnancy outcomes

A highly virulent variant of HIV-1 circulating in the Netherlands

We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV-CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences-is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence

A highly virulent variant of HIV-1 circulating in the Netherlands.

We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log &lt;sub&gt;10&lt;/sub&gt; increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV-CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences-is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence