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.
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Citation: PLoS One. 2016 Apr 22;11(4):e0154391. doi: 10.1371/journal.pone.0154391. eCollection 2016. Link to article on publisher's site
DOI of Published Version
UMCCTS funding, HIV-1, DNA replication, Viral replication, Infants, Blood plasma, Antiretroviral therapy, T cells, Polymerase chain reaction
McManus, Margaret M.; Mick, Eric O.; Hudson, Richard W. Jr.; Mofenson, Lynne M.; Sullivan, John L.; Somasundaran, Mohan; Luzuriaga, Katherine; and PACTG 356 Investigators, "Early Combination Antiretroviral Therapy Limits Exposure to HIV-1 Replication and Cell-Associated HIV-1 DNA Levels in Infants" (2016). Open Access Articles. 2910.
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