Search

Integrase inhibitors (INIs) are a potent option for HIV treatment. Limited data exist on INI resistance in West Africa, particularly in children living with HIV/AIDS. We determined the prevalence of integrase gene polymorphisms and the frequency of naturally occurring amino acid (aa) substitutions at positions associated with INI resistance. Dried blood spot (DBS) samples were obtained from one hundred and seven (107) HIV-1-infected children aged less than 15 years old in two West African countries, Benin and Mali. All children were naïve to INI treatment, 56 were naïve to anti-retroviral therapy (ART), and 51 had received ART. Genetic sequencing of HIV integrase was successful in 75 samples. The aa changes at integrase positions associated with INI resistance were examined according to the Stanford HIV Genotypic Resistance database. The median ages were 2.6 and 10 years for ART-naïve and -treated children, respectively. The most common subtypes observed were CRF02_AG (74.7%) followed by CRF06_cpx (20%). No major INI-resistance mutations at positions 66, 92, 121, 143, 147, 148, 155, and 263 were detected. The most prevalent INI accessory resistance mutations were: L74I/M (14/75, 18.6%) followed by E157Q (8/75, 10.6%), G163E/N/T/Q (5/75, 6.6%), Q95A/H/P (2/75, 2.6%), and T97A (4/75, 5.3%). Other substitutions observed were M50I/L/P, H51E/P/S/Q, I72V, T112V, V201I, and T206S. Polymorphisms at positions which may influence the genetic barrier and/or drive the selection of specific INI-resistance pathways were detected. However, no transmitted drug resistance (TDR) to INI was detected among samples of INI-naïve patients. These findings support the use of this treatment class for children with HIV-1, particularly in West Africa.

Background: Few biomarkers for sepsis diagnosis are commonly used in neonatal sepsis. Whilst host response is increasingly recognized in sepsis pathogenesis and prognosis, there is a need for evaluating the accuracy of new biomarkers targeting host response in regions where sepsis burden is high and medico-economic resources are scarce. The objective of the study is to evaluate diagnostic and prognostic accuracy of biomarkers of neonatal sepsis in Sub Saharan Africa. Methods: Prospective multicentre study conducted between April 2016 and March 2018 in three University hospitals and two sub-urbans healthcare centres in the south Benin region. Patients were followed from birth to 3 months of age. Accuracy of transcriptional (CD74, CX3CR1), proteic (PCT, IL-6, IL-10, IP-10) biomarkers and clinical characteristics to diagnose and prognose neonatal sepsis were measured. At delivery, cord blood from all consecutive newborns were sampled and analysed, and infants were followed for a 12 weeks’ period. Results: From April 17, 2016 through March 12, 2018, a total of 581 newborns were enrolled. One hundred and seventy-two newborns developed neonatal sepsis (29.6%) and death occurred in forty-nine infants (8.4%). Among all tested biomarkers and clinical criteria, CD74/IP-10 ratio showed the best accuracy for neonatal sepsis diagnosis, while PCT accuracy was low. Among biomarkers and clinical criteria studied, only CD74 and PCT were independently associated with mortality, with CD74 showing an elevated predictive accuracy. Conclusion: Cord blood PCT had a low accuracy for diagnosing early onset neonatal sepsis in Sub Saharan African neonates, while CD74/IP-10 ratio had the best diagnostic accuracy. CD74 expression at birth had the best accuracy in prognosing sepsis mortality.Trial registration: Clinicaltrial.gov registration number: NCT03780712. Registered 19 December 2018. Retrospectively registered

IntroductionNeonatal sepsis outreaches all causes of neonatal mortality worldwide and remains a major societal burden in low and middle income countries. In addition to limited resources, endemic morbidities, such as malaria and prematurity, predispose neonates and infants to invasive infection by altering neonatal immune response to pathogens. Nevertheless, thoughtful epidemiological, diagnostic and immunological evaluation of neonatal sepsis and the impact of gestational malaria have never been performed.Methods and analysisA prospective longitudinal multicentre follow-up of 580 infants from birth to 3 months of age in urban and suburban Benin will be performed. At delivery, and every other week, all children will be examined and clinically evaluated for occurrence of sepsis. At delivery, cord blood systematic analysis of selected plasma and transcriptomic biomarkers (procalcitonin, interleukin (IL)-6, IL-10, IP10, CD74 and CX3CR1) associated with sepsis pathophysiology will be evaluated in all live births as well as during the follow-up, and when sepsis will be suspected. In addition, whole blood response to selected innate stimuli and extensive peripheral blood mononuclear cells phenotypic characterisation will be performed. Reference intervals specific to sub-Saharan neonates will be determined from this cohort and biomarkers performances for neonatal sepsis diagnosis and prognosis tested.Ethics and disseminationEthical approval has been obtained from the Comité d’Ethique de la Recherche – Institut des Sciences Biomédicales Appliquées (CER-ISBA 85 - 5 April 2016, extended on 3 February 2017). Results will be disseminated through international presentations at scientific meetings and publications in peer-reviewed journals.Trial registration numberClinicalTrials.gov registration number: NCT03780712.