Intact HIV DNA decays in children with and without complete viral load suppression

Area of Science:

• Virology
• Immunology
• Pediatric Infectious Diseases

Background:

• HIV persistence during antiretroviral therapy (ART) is a major barrier to curing HIV in children.
• Understanding the dynamics of HIV reservoirs in children is crucial for developing effective cure strategies.

Purpose of the Study:

• To elucidate the dynamics and mechanisms of HIV persistence in children living with HIV (CWH) during ART.
• To investigate the decay kinetics of intact and defective HIV DNA and their relationship with immune responses.

Main Methods:

• Longitudinal study of 120 Kenyan CWH initiating ART between 1-12 months of age.
• Measurement of plasma HIV RNA, CD4+ T cell count, and intact/defective HIV DNA using the cross-subtype intact proviral DNA assay (CS-IPDA).
• Mathematical modeling to analyze decay kinetics of HIV RNA and DNA, and T cell receptor (TCR) beta clones.

Main Results:

• Early ART (0-1 year) showed rapid decay of plasma RNA and HIV DNA with half-lives of 3 months (intact) and 9 months (defective).
• After viral suppression (1-8 years), intact HIV DNA decay slowed (22-month half-life), while defective DNA decay ceased.
• Individual CD4+ TCRβ clones varied, but average kinetics aligned with defective DNA and CD4 count, suggesting selective pressures influence intact DNA decay.
• Brief ART interruptions were linked to transient HIV DNA rises but did not significantly impact long-term intact reservoirs.

Conclusions:

• HIV DNA decay kinetics in children on ART are biphasic, with slower decay of intact proviruses over longer periods.
• Differential decay rates of intact and defective HIV DNA are influenced by selective pressures on CD4+ T cells.
• Brief interruptions in ART may not substantially increase HIV reservoirs in children, offering insights for treatment strategies and potential cure interventions.