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Published on: March 30, 2014
Antiretroviral therapy is associated with a decrease in unintegrated HIV-1 DNA in pediatric patients
R M Donovan1, C E Bush, S M Smereck
1Department of Infectious Diseases, Henry Ford Hospital, Detroit, Michigan 48202.
Insights
Unintegrated HIV-1 DNA (uDNA) reliably decreases with antiretroviral therapy in children. This study suggests uDNA is a promising marker for monitoring treatment efficacy in pediatric HIV patients.
Area of Science:
- Virology
- Pediatric Infectious Diseases
- Immunology
Background:
- Effective monitoring of antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) is crucial for optimizing treatment outcomes.
- Current biomarkers for assessing ART efficacy in pediatric populations are limited, necessitating the evaluation of novel markers.
Purpose of the Study:
- To investigate the impact of ART on various markers of HIV-1, including unintegrated DNA (uDNA), integrated DNA (iDNA), immune complex dissociated (ICD) p24 antigenemia, and plasma viral titer.
- To identify reliable indicators for monitoring ART efficacy in children living with HIV-1.
Main Methods:
- Longitudinal study of seven children initiating ART, with sample collection at baseline, 3 months, and 10 months.
- Quantification of HIV-1 uDNA, iDNA, ICD p24 antigen, and plasma viral load at each time point.
- Statistical analysis to assess changes in measured parameters following ART initiation.
Main Results:
- A significant decrease in the percentage of HIV-1 uDNA was observed, from an average of 43% at baseline to 18% at 3 months (p=0.01) and 1% at 10 months.
- HIV-1 iDNA levels remained relatively constant throughout the study period.
- ICD p24 antigen levels showed variable responses, decreasing in three patients and remaining unchanged in four.
- Plasma viral cultures were positive in only one child pre-therapy.
Conclusions:
- Measurement of HIV-1 uDNA is a reliable indicator that decreases following nucleoside-based antiretroviral therapy in children.
- Unintegrated HIV-1 DNA shows potential as a valuable biomarker for monitoring ART efficacy in pediatric HIV management.
Abstract:
Good markers for monitoring the efficacy of antiretroviral therapy in children do not currently exist. This study examined the effect of antiretroviral therapy on human immunodeficiency virus (HIV-1) unintegrated DNA (uDNA), integrated DNA (iDNA), percent uDNA, immune complex dissociated (ICD) p24 antigenemia, and plasma viral titer. Seven children were followed at therapy initiation and at approximately 3- and 10-month intervals. HIV-1 uDNA was detected in all children prior to start of therapy (average percent uDNA, 43%). At 3 months, the percent HIV uDNA decreased in all patients to an average of 18% (p = 0.01) and at 10 months decreased to an average of 1%. In contrast, the amount of HIV iDNA was relatively constant after initiation of therapy. ICD HIV p24 antigen was detected in all patients prior to therapy (average, 538 pg/ml). Over the study period, the ICD p24 antigen level decreased in three patients and remained relatively unchanged in four patients. Plasma cultures of HIV-1 were positive in only one of the seven patients prior to therapy. Among the methods evaluated, measurement of uDNA was the only parameter which reliable decreased after initiation of nucleoside therapy.
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