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Published on: August 31, 2014
Predictors of intact HIV DNA levels among children in Kenya
Jillian Neary1, Carolyn S Fish2, Noah A J Cassidy2
1Department of Epidemiology, University of Washington.
Insights
Predictors of HIV DNA in children on antiretroviral therapy (ART) were identified. Lower pre-ART CD4+ percentage and higher cytomegalovirus (CMV) viral load predicted higher intact HIV DNA levels.
Area of Science:
- Virology
- Immunology
- Pediatric Infectious Diseases
Background:
- Understanding HIV persistence in children is crucial for eradication strategies.
- Antiretroviral therapy (ART) initiated in infancy can suppress viral replication but does not eliminate the HIV DNA reservoir.
- Factors influencing the establishment and maintenance of the HIV reservoir in pediatric populations require further investigation.
Purpose of the Study:
- To identify predictors of intact (replication-competent) and total (intact and defective) HIV DNA levels in the reservoir among children initiating ART before one year of age.
- To analyze the association of pre-ART immune status, viral load, and ART regimen with HIV DNA reservoir size.
Main Methods:
- Longitudinal quantification of intact and total HIV DNA using a novel cross-subtype intact proviral DNA assay.
- Measurement of pre-ART cytomegalovirus (CMV) viral load via quantitative PCR.
- Analysis using linear mixed-effects models to determine predictors of HIV DNA levels (log10 copies/million).
Main Results:
- Lower pre-ART CD4+ percentage and higher HIV RNA predicted higher total HIV DNA levels.
- Higher pre-ART CD4+ percentage, higher CMV viral load, and protease inhibitor-based ART regimens predicted higher intact HIV DNA levels.
- 86% of the 65 children studied had CMV viremia prior to ART initiation.
Conclusions:
- Pre-ART immunosuppression (indicated by CD4+ percentage), cytomegalovirus (CMV) viral load, and the choice of first-line ART regimen are significant factors influencing the establishment and persistence of intact HIV DNA in the reservoir.
- These findings highlight potential targets for interventions aimed at reducing the viral reservoir in children with HIV.
Objective:
We determined predictors of both intact (estimate of replication-competent) and total (intact and defective) HIV DNA in the reservoir among children with HIV.
Design:
HIV DNA in the reservoir was quantified longitudinally in children who initiated antiretroviral therapy (ART) at less than 1 year of age using a novel cross-subtype intact proviral DNA assay that measures both intact and total proviruses. Quantitative PCR was used to measure pre-ART cytomegalovirus (CMV) viral load. Linear mixed effects models were used to determine predictors of intact and total HIV DNA levels (log 10 copies/million).
Results:
Among 65 children, median age at ART initiation was 5 months and median follow-up was 5.2 years; 86% of children had CMV viremia pre-ART. Lower pre-ART CD4 + percentage [adjusted relative risk (aRR): 0.87, 95% confidence intervals (95% CI): 0.79-0.97; P = 0.009] and higher HIV RNA (aRR: 1.21, 95% CI: 1.06-1.39; P = 0.004) predicted higher levels of total HIV DNA during ART. Pre-ART CD4 + percentage (aRR: 0.76, 95% CI: 0.65-0.89; P < 0.001), CMV viral load (aRR: 1.16, 95% CI: 1.01-1.34; P = 0.041), and first-line protease inhibitor-based regimens compared with nonnucleoside reverse transcriptase-based regimens (aRR: 1.36, 95% CI: 1.04-1.77; P = 0.025) predicted higher levels of intact HIV DNA.
Conclusion:
Pre-ART immunosuppression, first-line ART regimen, and CMV viral load may influence establishment and sustainment of intact HIV DNA in the reservoir.
