RESUMEN
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
RESUMEN
Female children and adults typically generate more efficacious immune responses to vaccines and infections than age-matched males, but also suffer greater immunopathology and autoimmune disease. We here describe, in a cohort of > 170 in utero HIV-infected infants from KwaZulu-Natal, South Africa, fetal immune sex differences resulting in a 1.5-2-fold increased female susceptibility to intrauterine HIV infection. Viruses transmitted to females have lower replicative capacity (p = 0.0005) and are more type I interferon-resistant (p = 0.007) than those transmitted to males. Cord blood cells from females of HIV-uninfected sex-discordant twins are more activated (p = 0.01) and more susceptible to HIV infection in vitro (p = 0.03). Sex differences in outcome include superior maintenance of aviraemia among males (p = 0.007) that is not explained by differential antiretroviral therapy adherence. These data demonstrate sex-specific innate immune selection of HIV associated with increased female susceptibility to in utero infection and enhanced functional cure potential among infected males.
Asunto(s)
Infecciones por VIH/inmunología , VIH-1/inmunología , VIH-1/patogenicidad , Inmunidad Innata/fisiología , Antirretrovirales/uso terapéutico , Estudios de Cohortes , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/metabolismo , VIH-1/efectos de los fármacos , Humanos , Inmunidad Innata/genética , Transmisión Vertical de Enfermedad Infecciosa , Interferones/metabolismo , Estimación de Kaplan-Meier , Masculino , Filogenia , Factores Sexuales , Investigación Biomédica TraslacionalRESUMEN
OBJECTIVE: To evaluate safety and haematological effects of delayed cord clamping (DCC) in infants with expected low birthweight born in a resource-poor setting. METHODS: Randomised controlled trial involving pregnant women in early labour ≥18 years with intrapartum symphysal-fundal height ≤32 cm. Mothers were randomised for either early cord clamping (ECC, <30 s) or DCC (2-3 min after birth). RESULTS: We included 104 vigorous infants born by vaginal delivery, of whom 39% had a birthweight <2500 g. Infant haemoglobin (Hb) levels 24 h after birth were significantly higher in the DCC group (18.0 g/dl vs. 16.8 g/dl, P = 0.006). Despite successful placental transfusion, hyperbilirubinemia and hyperviscosity were not observed. Two months after birth, there were no differences in Hb between groups (9.9 g/dl vs. 9.8 g/dl, P = 0.60), but the infants in the DCC group had better weight gain from baseline than those with ECC (2.2 kg vs. 1.9 kg, P = 0.058). CONCLUSIONS: In this South African cohort of newborns with a subnormal distribution of birthweight delayed cord clamping was a safe procedure. Two months after birth the effect of DCC on Hb was not detectable anymore. DCC should be promoted in every singleton delivery in a resource-poor setting irrespective of the birthweight.
