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

PLoS One. 2016 Apr 22;11(4):e0154391. doi: 10.1371/journal.pone.0154391. eCollection 2016.


The primary aim of this study was to measure HIV-1 persistence following combination antiretroviral therapy (cART) in infants and children. Peripheral blood mononuclear cell (PBMC) HIV-1 DNA was quantified prior to and after 1 year of cART in 30 children, stratified by time of initiation (early, age <3 months, ET; late, age >3 months-2 years, LT). Pre-therapy PBMC HIV-1 DNA levels correlated with pre-therapy plasma HIV-1 levels (r = 0.59, p<0.001), remaining statistically significant (p = 0.002) after adjustment for prior perinatal antiretroviral exposure and age at cART initiation. PBMC HIV-1 DNA declined significantly after 1 year of cART (Overall: -0.91±0.08 log10 copies per million PBMC, p<0.001; ET: -1.04±0.11 log10 DNA copies per million PBMC, p<0.001; LT: -0.74 ±0.13 log10 DNA copies per million PBMC, p<0.001) but rates of decline did not differ significantly between ET and LT. HIV-1 replication exposure over the first 12 months of cART, estimated as area-under-the-curve (AUC) of circulating plasma HIV-1 RNA levels, was significantly associated with PBMC HIV-1 DNA at one year (r = 0.51, p = 0.004). In 21 children with sustained virologic suppression after 1 year of cART, PBMC HIV-1 DNA levels continued to decline between years 1 and 4 (slope -0.21 log10 DNA copies per million PBMC per year); decline slopes did not differ significantly between ET and LT. PBMC HIV-1 DNA levels at 1 year and 4 years of cART correlated with age at cART initiation (1 year: p = 0.04; 4 years: p = 0.03) and age at virologic control (1 and 4 years, p = 0.02). Altogether, these data indicate that reducing exposure to HIV-1 replication and younger age at cART initiation are associated with lower HIV-1 DNA levels at and after one year of age, supporting the concept that HIV-1 diagnosis and cART initiation in infants should occur as early as possible.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Retroviral Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active
  • Child, Preschool
  • DNA Copy Number Variations
  • DNA, Viral / antagonists & inhibitors*
  • DNA, Viral / biosynthesis
  • DNA, Viral / genetics
  • Female
  • HIV Infections / diagnosis
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV-1 / drug effects*
  • HIV-1 / physiology
  • Humans
  • Infant
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / virology
  • Longitudinal Studies
  • Male
  • RNA, Viral / antagonists & inhibitors*
  • RNA, Viral / biosynthesis
  • RNA, Viral / genetics
  • Time-to-Treatment
  • Treatment Outcome
  • Viral Load / drug effects
  • Virus Replication / drug effects*
  • Virus Replication / genetics


  • Anti-Retroviral Agents
  • DNA, Viral
  • RNA, Viral