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Evolution of human immunodeficiency virus type 1 in perinatally infected infants with rapid and slow progression to disease.

ABSTRACT: We addressed the relationship between the origin and evolution of human immunodeficiency virus type 1 (HIV-1) variants and disease outcome in perinatally infected infants by studying the V3 regions of viral variants in samples obtained from five transmitting mothers at delivery and obtained sequentially over the first year of life from their infected infants, two of whom (rapid progressors) rapidly progressed to having AIDS. Phylogenetic analyses disclosed that the V3 sequences from each mother-infant pair clustered together and were clearly distinct from those of the other pairs. Within each pair, the child's sequences formed a monophyletic group, indicating that a single variant initiated the infection in both rapid and slow progressors. Plasma HIV-1 RNA levels increased in all five infants during their first months of life and then declined within the first semester of life only in the three slow progressors. V3 variability increased over time in all infants, but no differences in the pattern of V3 evolution in terms of potential viral phenotype were observed. The numbers of synonymous and nonsynonymous substitutions varied during the first semester of life regardless of viral load, CD4+-cell count, and disease progression. Conversely, during the second semester of life the rate of nonsynonymous substitutions was higher than that of synonymous substitutions in the slow progressors but not in the rapid progressors, thus suggesting a stronger host selective pressure in the former. In view of the proposal that V3 genetic evolution is driven mainly by host immune constraints, these findings suggest that while the immune response to V3 might contribute to regulating viral levels after the first semester of life, it is unlikely to play a determinant role in the initial viral decline soon after birth.

SUBMITTER: Salvatori F

PROVIDER: S-EPMC191691 | biostudies-other | 1997 Jun

REPOSITORIES: biostudies-other

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Evolution of human immunodeficiency virus type 1 in perinatally infected infants with rapid and slow progression to disease.

Salvatori F F Masiero S S Giaquinto C C Wade C M CM Brown A J AJ Chieco-Bianchi L L De Rossi A A

Journal of virology 19970601 6

We addressed the relationship between the origin and evolution of human immunodeficiency virus type 1 (HIV-1) variants and disease outcome in perinatally infected infants by studying the V3 regions of viral variants in samples obtained from five transmitting mothers at delivery and obtained sequentially over the first year of life from their infected infants, two of whom (rapid progressors) rapidly progressed to having AIDS. Phylogenetic analyses disclosed that the V3 sequences from each mother- ...[more]

PMID: 9151863

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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.

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Evolution of human immunodeficiency virus type 1 in perinatally infected infants with rapid and slow progression to disease.

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Evolution of human immunodeficiency virus type 1 in perinatally infected infants with rapid and slow progression to disease.

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