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Early Combination Antiretroviral Therapy Limits Exposure to HIV-1 Replication and Cell-Associated HIV-1 DNA Levels in

Margaret McManus1, Eric Mick2, Richard Hudson1

  • 1Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.

Plos One
|April 23, 2016
PubMed

Insights

Early combination antiretroviral therapy (cART) initiation in infants and children with HIV-1 is linked to lower viral DNA persistence. Initiating cART earlier in life is crucial for reducing long-term HIV-1 DNA levels in children.

Area of Science:

  • Pediatric Infectious Diseases
  • Virology
  • Immunology

Background:

  • HIV-1 persistence in children on combination antiretroviral therapy (cART) remains a significant challenge.
  • Understanding factors influencing HIV-1 DNA levels post-therapy is crucial for optimizing treatment strategies in pediatric populations.

Purpose of the Study:

  • To quantify HIV-1 DNA persistence in peripheral blood mononuclear cells (PBMCs) of infants and children after one year of cART.
  • To evaluate the impact of early versus late cART initiation on HIV-1 DNA levels and decline rates.
  • To assess the association between HIV-1 replication exposure and PBMC HIV-1 DNA levels.

Main Methods:

  • Quantification of PBMC HIV-1 DNA before and after one year of cART in 30 children.
  • Stratification of children into early (ET, <3 months) and late (LT, >3 months-2 years) cART initiation groups.
  • Analysis of plasma HIV-1 RNA levels (AUC) to estimate viral replication exposure.

Main Results:

  • PBMC HIV-1 DNA levels significantly declined after one year of cART in both ET and LT groups, with no significant difference in decline rates between groups.
  • Higher pre-therapy PBMC HIV-1 DNA levels correlated with higher pre-therapy plasma HIV-1 levels.
  • HIV-1 replication exposure during the first year of cART was significantly associated with higher PBMC HIV-1 DNA levels at one year.
  • PBMC HIV-1 DNA levels at 1 and 4 years of cART correlated with younger age at cART initiation and virologic control.

Conclusions:

  • Reducing HIV-1 replication exposure and initiating cART at a younger age are associated with lower PBMC HIV-1 DNA levels in children.
  • These findings support the early diagnosis and initiation of cART in infants to minimize HIV-1 persistence.
  • Earlier cART initiation may lead to better long-term control of HIV-1 reservoirs in children.

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