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Clinical significance of human immunodeficiency virus type 1 phenotypes in infected children
L T Spencer1, M T Ogino, W M Dankner
1Department of Pediatrics, University of California, San Diego.
Insights
Human immunodeficiency virus type 1 (HIV-1) infection in children shows varied progression. Infants with non-syncytium-inducing (NSI) HIV-1 face rapid AIDS progression, while older children with syncytium-inducing (SI) HIV-1 exhibit lower CD4 counts and zidovudine resistance.
Area of Science:
- Virology
- Pediatric Infectious Diseases
- Immunology
Background:
- Perinatally acquired human immunodeficiency virus type 1 (HIV-1) infection presents diverse clinical trajectories in children.
- Understanding the viral phenotype, specifically syncytium-inducing (SI) capacity, is crucial for predicting disease progression and treatment response.
Purpose of the Study:
- To investigate the association between HIV-1 phenotype (SI vs. non-syncytium-inducing, NSI) and clinical outcomes in perinatally infected infants and children.
- To determine if viral phenotype correlates with CD4+ T-cell counts, age at diagnosis, and in vitro zidovudine resistance.
Main Methods:
- Analysis of HIV-1 isolates from perinatally infected infants (<1 year) and children (>2 years) to determine syncytium-inducing (SI) or non-syncytium-inducing (NSI) phenotype.
- Correlation of viral phenotype with age, CD4+ T-cell counts, and in vitro zidovudine resistance.
Main Results:
- All infants (<1 year) exhibited NSI HIV-1 phenotypes; 10 progressed to AIDS and 3 died within the first year.
- Among children (>2 years), 13 had SI HIV-1 and 13 had NSI strains. SI strains were associated with significantly lower CD4+ counts and older age.
- Children with SI strains were more likely to demonstrate in vitro zidovudine resistance.
Conclusions:
- HIV-1 infection in children may follow a biphasic course, with rapid progression in infants with NSI strains.
- Older children tend to develop SI HIV-1 phenotypes, correlating with lower CD4+ counts and increased zidovudine resistance.
- Viral phenotype is a significant factor influencing disease progression and therapeutic response in pediatric HIV-1 infection.
Abstract:
Human immunodeficiency virus type 1 (HIV-1) isolates from perinatally infected infants and children were examined for syncytium-inducing (SI) capacity. All isolates from 14 infants < 1 year old had non-syncytium-inducing (NSI) HIV-1 phenotypes. Within their first year, 10 infants progressed to AIDS and 3 died. Of isolates from 26 children > 2 years old, 13 had SI HIV-1 phenotypes and 13 had NSI strains. Children with SI virus had significantly lower CD4+ cell counts standardized for age and were significantly older than those with NSI strains (P = .008 and .001, respectively); the effect of viral phenotype on CD4+ lymphocytes could not be detected independent of age. In another group, children with SI strains were more likely to show in vitro zidovudine resistance. Results suggest a biphasic response to HIV infection in children. Progression to AIDS may occur rapidly in infants with NSI HIV-1, but older children tend to have SI phenotypes and lower CD4+ lymphocyte counts and more often show zidovudine resistance.