Abstract
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.
Highlights
Control of HIV-1 replication following the initiation of combination antiretroviral therapy in the first few months following birth preserves CD4+ T cell counts and general immune function and prevents HIV-1 associated disease progression in infants [1, 2]
Pre-therapy Peripheral blood mononuclear cell (PBMC) HIV-1 log10 DNA levels correlated with pre-therapy plasma log10 HIV-1 RNA levels (r = 0.59, p
Serial measurement of PBMC HIV-1 DNA levels in children with sustained virologic response allowed for the evaluation of continued decay of PBMC HIV-1 DNA levels up to 4 years following cART
Summary
Control of HIV-1 replication following the initiation of combination antiretroviral therapy (cART) in the first few months following birth preserves CD4+ T cell counts and general immune function and prevents HIV-1 associated disease progression in infants [1, 2]. While cART may control HIV-1 replication to the point that plasma HIV-1 RNA levels are undetectable by routine and ultrasensitive assays, HIV-1 DNA remains detectable in circulating CD4+ T cells. Data quantifying HIV-1 persistence in children before and immediately following early cART are limited. We undertook this study to quantify PBMC HIV-1 DNA levels before and up to four years following early cART in children, with the specific goal of examining the relationships between circulating PBMC HIV-1 DNA levels to the timing of cART initiation and the duration of viremic exposure over the first year of treatment
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
