Early Combination Antiretroviral Therapy Limits Exposure to HIV-1 Replication and Cell-Associated HIV-1 DNA Levels in Infants.
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.
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
Margaret
M
McManus
Department of Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
Eric
E
Mick
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
Richard
R
Hudson
The Elizabeth Glaser Pediatric AIDS Foundation, Washington DC, United States of America.
Lynne M
LM
Mofenson
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
John L
JL
Sullivan
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
Mohan
M
Somasundaran
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America.
Katherine
K
Luzuriaga
D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D002675:Child, Preschool; D056915:DNA Copy Number Variations; D004279:DNA, Viral / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D015658:HIV Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007223:Infant; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000821:virology; D008137:Longitudinal Studies; D008297:Male; D012367:RNA, Viral / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D061665:Time-to-Treatment; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects* / Q000235:genetics
D044966:Anti-Retroviral Agents; D004279:DNA, Viral; D012367:RNA, Viral