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Predictive markers of clinical outcome in vertically HIV-1-infected infants. A prospective longitudinal study
S Resino1, D Gurbindo, J M Cano
1Division of Immunology, Hospital General Universitario Gregorio Marañón, Madrid, Spain.
Insights
Key HIV-1 markers like CD4+ T cells, CD8+ T cells, and viral load predict disease progression in infants. Lower T cell percentages and higher viral loads indicate a worse prognosis and faster advancement to AIDS.
Area of Science:
- Immunology
- Virology
- Pediatrics
Background:
- Human Immunodeficiency Virus type 1 (HIV-1) infection in infants poses significant health challenges.
- Early identification of disease progression markers is crucial for timely intervention.
Purpose of the Study:
- To investigate the relationship between immunologic and virologic markers and disease progression in HIV-1-infected infants.
- To identify predictive markers for rapid advancement to acquired immunodeficiency syndrome (AIDS).
Main Methods:
- Longitudinal collection of plasma samples from infants born to HIV-1-infected mothers.
- Assay of viral load, viral phenotype, and lymphocyte populations (CD4+ and CD8+ T cells) over time.
- Statistical analysis to determine the association between marker levels and disease progression to AIDS.
Main Results:
- Lower CD4+ T cell percentages (<25%) were associated with a 3.35-fold increased risk of AIDS progression (p=0.05).
- Lower CD8+ T cell percentages (<25%) correlated with a 4.95-fold increased risk of AIDS progression (p=0.03).
- Higher viral loads (>5.5 log10 copies/mL) significantly increased the risk of AIDS progression by 23.72-fold (p=0.0001).
- Changes in viral replication rate and phenotype also indicated disease advancement.
Conclusions:
- CD4+ and CD8+ T-lymphocyte percentages, viral load, and viral phenotype are significant predictors of rapid HIV-1 disease progression in infants.
- These markers can aid in identifying infants at high risk for developing advanced HIV-1 disease and AIDS.
Abstract:
We have investigated the relationship between disease progression and several immunologic and virologic markers of HIV infection. Plasma samples from infants born to HIV-1-infected mothers were collected at birth and at 1, 2, 4, 6, 9, 12, 15, and 18 mo of age and subsequently were assayed every 6 mo for viral load, viral phenotype, and lymphocyte populations. A cutoff level of 25% indicative of a preserved immunologic status, both of CD4+ and CD8+ blood T cells, was associated with significant differences in disease progression (p = 0.04 and 0.02, respectively). Infants with median CD4+ T cells <25% had a relative risk of progression to AIDS 3.35-fold higher than those with CD4+ above this level (p = 0.05). The relative risk of progression to AIDS for infants with median CD8+ <25% was 4.95-fold higher than for those with CD8+ percent above this threshold (p = 0.03). Similarly, a cutoff level of viral load of 5.5 log10 copies/mL was indicative of a worse prognosis. Infants with median viral load >5.5 log10 copies/mL had a relative risk of progression to AIDS 23.72-fold higher (p = 0.0001) than those with median viral load below this threshold. Interestingly, changes from a slow replication and low titer to a rapid replication and high titer of virus and from nonsyncytium-inducing to syncytium-inducing viral phenotype were indicative of progression to AIDS. Our results indicate that biologic phenotype of viral isolates and CD8+ T-lymphocyte percentages in peripheral blood as well as viral load and CD4+ T-lymphocyte percentages could predict rapid progression to advanced HIV-1 disease in HIV-1-infected infants.