Dataset Information

Purifying Selection in Human Immunodeficiency Virus-1 pol Gene in Perinatally Human Immunodeficiency Virus-1-Infected Children Harboring Discordant Immunological Response and Virological Nonresponse to Long-Term Antiretroviral Therapy.

ABSTRACT: Background:Biological monitoring of antiretroviral treatment (ART) in human immunodeficiency virus (HIV)-infected pediatric population remains challenging. The aim of the present study was to assess the long-term HIV-1 genetic diversity in pol gene in HIV-1-infected children in virological failure under antiretroviral regimen adapted according to the successive World Health Organization (WHO) guidelines for resource-constrained settings. Methods:HIV-1 diversity in pol gene was assessed in HIV-1-infected children and adolescents born from HIV-infected mothers (median age at follow-up: 13.8 years) in virological failure (VF+) despite long-term regimen recommended by the WHO. The numbers of nonsynonymous substitutions per potential nonsynonymous site (dN) and of synonymous substitutions at potential synonymous sites (dS) in HIV-1 pol gene and the dN/dS ratios were used to estimate the selective pressure on circulating HIV-1. Results:The immunological responses to ART basically corresponded to: 1) Full therapeutic failure with immunological (I-) and virological nonresponses in one-quarter (24.6%) of study children ((I-, VF+) subgroup); 2) Discordant immunovirological responses with paradoxical high CD4 T cell counts (I+) and high HIV-1 RNA load in the remaining cohort patients (75.4%) ((I+, VF+) subgroup). The mean dS was 1.8-fold higher in (I+, VF+) than (I-, VF+) subgroup (25.9 ± 18.4 vs. 14.3 ± 10.8). In the (I+, VF+) subgroup, the mean dS was 1.6-fold higher than the mean dN. Finally, the mean dN/dS ratio was 2.1-fold lower in (I+, VF+) than (I-, VF+) subgroup (0.6 ± 0.3 vs. 1.3 ± 0.7), indicating purifying selection in the immunovirological discordant (I+, VF+) subgroup and positive selection in the immunovirological failure (I-, VF+) subgroup. Conclusions:Children and adolescents in immunovirological therapeutic failure harbor positive selection of HIV-1 strains favoring diversifying in pol-encoded amino acids. In contrast, children with persistent discordant immunovirological responses show accumulation of mutations and purifying selection in pol gene sequences, indicating limited genetic evolution and likely suggesting genetic adaptation of viruses to host functional constraints.

SUBMITTER: Mboumba Bouassa RS

PROVIDER: S-EPMC7295550 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Purifying Selection in Human Immunodeficiency Virus-1 <i>pol</i> Gene in Perinatally Human Immunodeficiency Virus-1-Infected Children Harboring Discordant Immunological Response and Virological Nonresponse to Long-Term Antiretroviral Therapy.

Mboumba Bouassa Ralph-Sydney RS Pere Helene H Mossoro-Kpinde Christian Diamant CD Roques Pierre P Gody Jean Chrysostome JC Moussa Sandrine S Veyer David D Gresenguet Gerard G Charpentier Charlotte C Jenabian Mohammad-Ali MA Djoba Siawaya Joel Fleury JF Belec Laurent L

Journal of clinical medicine research 20200604 6

<h4>Background</h4>Biological monitoring of antiretroviral treatment (ART) in human immunodeficiency virus (HIV)-infected pediatric population remains challenging. The aim of the present study was to assess the long-term HIV-1 genetic diversity in <i>pol</i> gene in HIV-1-infected children in virological failure under antiretroviral regimen adapted according to the successive World Health Organization (WHO) guidelines for resource-constrained settings.<h4>Methods</h4>HIV-1 diversity in <i>pol</i ...[more]

PMID: 32587653

Similar Datasets

Project description:BackgroundFatigue is common among adults living with human immunodeficiency virus (HIV) as well as children with a chronic disease (CCD). Fatigue can have disastrous effects on health status, including health related quality of life (HRQOL). Even so, fatigue is underexplored in children and adolescents perinatally infected with HIV (PHIV+) in the Netherlands. The objective of this observational study is to explore fatigue in PHIV+ and its association with their HRQOL.MethodsWe measured HRQOL and fatigue using the Pediatric Quality of Life Inventory™ (PedsQL 4.0) and the PedsQL Multidimensional Fatigue Scale (MFS). The PedsQL MFS encompasses three subscales: general fatigue, sleep/rest fatigue and cognitive fatigue, and a total fatigue score. We compared outcomes of PHIV+ children and adolescents in the Amsterdam University Medical Centre with three groups: 1) HIV-uninfected controls (HIV-) matched for age, sex, region of birth, socioeconomic status and adoption status, 2) CCD, and 3) the general Dutch population. Within the PHIV+ group we explored associations between fatigue and HRQOL.ResultsWe enrolled 14 PHIV+ (median age 10.2 years [IQR 9.2-11.4]) and 14 HIV-. Compared to CCD, PHIV+ significantly reported less general fatigue (mean difference 13.0, 95% CI 1.3 to 24.8). PHIV+ did not score significantly different on any of the other PedsQL MFS scales compared to HIV-, CCD or the general Dutch population. PHIV children scored relatively low on the cognitive fatigue scale in comparison to HIV-uninfected matched controls, CCD and the general population, although these differences did not reach significance. Among PHIV+, a lower score on total fatigue, general fatigue and cognitive fatigue was associated with a lower HRQOL score.ConclusionsThe results of this study suggest that PHIV children and adolescents do not experience more symptoms of fatigue than their healthy peers. However, PHIV children and adolescents may be more likely to experience cognitive fatigue. Fatigue in PHIV also appears to be associated with children's HRQOL. Further research should confirm these exploratory findings.

Project description:ObjectiveTo evaluate associations between human immunodeficiency virus (HIV) disease severity and psychiatric and functional outcomes in youth with perinatal HIV infection.DesignCross-sectional analysis of entry data from an observational,prospective 2-year study.Logistic and linear regression models adjusted for potential confounders were used.SettingTwenty-nine sites of the International Maternal Pediatrics Adolescent AIDS Clinical Trials Group study in the United States and Puerto Rico.ParticipantsYouth aged 6 to 17 years who had HIV infection (N=319).Main exposuresAntiretroviral treatment and perinatal HIV infection.Main outcome measuresYouth and primary caregivers were administered an extensive battery of measures that assessed psychiatric symptoms; cognitive, social,and academic functioning; and quality of life.ResultsCharacteristics of HIV were a current CD4 percentage of 25% or greater (74% of participants), HIV RNA levels of less than 400 copies/mL (59%), and current highly active antiretroviral therapy (81%). Analyses indicated associations of past and current Centers for Disease Control and Prevention class C designation with less severe attention-deficit/hyperactivity disorder inattention symptoms,older age at nadir CD4 percentage and lower CD4 percentage at study entry with more severe conduct disorder symptoms,higher RNA viral load at study entry with more severe depression symptoms, and lower CD4 percentage atstudy entry with less severe symptoms of depression. There was little evidence of an association between specific antiretroviral therapy and severity of psychiatric symptoms.A lower nadir CD4 percentage was associated with lower quality of life, worse Wechsler Intelligence Scale for Children Coding Recall scores, and worse social functioning.ConclusionHuman immunodeficiency virus illness severity markers are associated with the severity of some psychiatric symptoms and, notably, with cognitive, academic,and social functioning, all of which warrant additional study.

Dataset Information

Purifying Selection in Human Immunodeficiency Virus-1 pol Gene in Perinatally Human Immunodeficiency Virus-1-Infected Children Harboring Discordant Immunological Response and Virological Nonresponse to Long-Term Antiretroviral Therapy.

Publications

Purifying Selection in Human Immunodeficiency Virus-1 <i>pol</i> Gene in Perinatally Human Immunodeficiency Virus-1-Infected Children Harboring Discordant Immunological Response and Virological Nonresponse to Long-Term Antiretroviral Therapy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets