Program in Molecular Medicine; Department of Quantitative Health Sciences; Department of Pediatrics, Division of Immunology/Infectious Disease
Immunology and Infectious Disease | Immunoprophylaxis and Therapy | Infectious Disease | Pediatrics | Virus Diseases
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.
UMCCTS funding, HIV-1, DNA replication, Viral replication, Infants, Blood plasma, Antiretroviral therapy, T cells, Polymerase chain reaction
DOI of Published Version
PLoS One. 2016 Apr 22;11(4):e0154391. doi: 10.1371/journal.pone.0154391. eCollection 2016. Link to article on publisher's site
McManus MM, Mick EO, Hudson RW, Mofenson LM, Sullivan JL, Somasundaran M, Luzuriaga K, PACTG 356 Investigators. (2016). Early Combination Antiretroviral Therapy Limits Exposure to HIV-1 Replication and Cell-Associated HIV-1 DNA Levels in Infants. Open Access Articles. https://doi.org/10.1371/journal.pone.0154391. Retrieved from https://escholarship.umassmed.edu/oapubs/2910
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