ABSTRACT
INTRODUCTION: Mutations associated with HIV drug resistance (DR) affect clinical outcomes. Understanding the prevalence of HIV DR and its association with viral suppression and survival in the paediatric population is key to inform patient care and health policies. METHODS: We used Brazilian monitoring systems to identify genotyping tests performed in children living with HIV aged ≤18 months between 2009 and 2020. We categorized HIV DR using three criteria: any HIV DR (R1), DR to nevirapine or efavirenz (R2), and DR to at least one antiretroviral recommended for children with HIV in Brazilian guidelines (R3). We investigated factors associated with HIV DR, viral suppression, and survival up to 3 years old using multivariable models. Lastly, we describe the annual prevalence of each type of HIV DR in Brazilian children with HIV between 2009 and 2020. RESULTS: We included 1152 children with HIV with a median age of 5 months at genotype testing; 57% were females. R1 was observed in 30%, R2 in 17%, and R3 in 21%. Children with HIV whose birth parents were exposed to nevirapine or efavirenz before delivery had higher odds of R2 (odds ratio 3.4; 95% confidence interval [CI] 1.1-10.8). Children with HIV with R1 or R3 had higher rates of death than those with HIV with no HIV DR in the adjusted models (adjusted hazard ratios 4.7 [95% CI 1.6-13.9] and 4.1 [95% CI 1.4-12.4], respectively). The prevalence of resistance to nevirapine and efavirenz peaked in 2015. Over time, the prevalence of genotyping tests with no detected resistance varied between 57% and 87%. CONCLUSION: HIV DR is highly prevalent in children with HIV and is associated with lower survival.
ABSTRACT
Heteroxenic and monoxenic trypanosomatids were screened for the presence of actin using a mouse polyclonal antibody produced against the entire sequence of the Trypanosoma cruzi actin gene, encoding a 41.9 kDa protein. Western blot analysis showed that this antibody reacted with a polypeptide of approximately 42 kDa in the whole-cell lysates of parasites targeting mammals (T. cruzi, Trypanosoma brucei and Leishmania major), insects (Angomonas deanei, Crithidia fasciculata, Herpetomonas samuelpessoai and Strigomonas culicis) and plants (Phytomonas serpens). A single polypeptide of approximately 42 kDa was detected in the whole-cell lysates of T. cruzi cultured epimastigotes, metacyclic trypomastigotes and amastigotes at similar protein expression levels. Confocal microscopy showed that actin was expressed throughout the cytoplasm of all the tested trypanosomatids. These data demonstrate that actin expression is widespread in trypanosomatids.
Subject(s)
Actins/metabolism , Trypanosomatina/metabolism , Animals , Blotting, Western , Electrophoresis, Polyacrylamide Gel , Fluorescent Antibody Technique , Mice , Microscopy, Confocal , Protozoan Proteins/metabolismABSTRACT
Heteroxenic and monoxenic trypanosomatids were screened for the presence of actin using a mouse polyclonal antibody produced against the entire sequence of the Trypanosoma cruzi actin gene, encoding a 41.9 kDa protein. Western blot analysis showed that this antibody reacted with a polypeptide of approximately 42 kDa in the whole-cell lysates of parasites targeting mammals (T. cruzi, Trypanosoma brucei and Leishmania major), insects (Angomonas deanei, Crithidia fasciculata, Herpetomonas samuelpessoai and Strigomonas culicis) and plants (Phytomonas serpens). A single polypeptide of approximately 42 kDa was detected in the whole-cell lysates of T. cruzi cultured epimastigotes, metacyclic trypomastigotes and amastigotes at similar protein expression levels. Confocal microscopy showed that actin was expressed throughout the cytoplasm of all the tested trypanosomatids. These data demonstrate that actin expression is widespread in trypanosomatids.