The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH

The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. DNA declined significantly after 1 year of cART (Overall: -0.910.08 log10 copies per million PBMC, p 0.001; ET: -1.040.11 log10 DNA copies per Cetrimonium Bromide(CTAB) 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 more youthful 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. Introduction 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]. Early combination antiretroviral therapy can also markedly reduce HIV-1 associated mortality [3]. Current guidelines [4, 5] thus recommend early infant diagnosis and the immediate initiation of cART in all HIV-1 infected infants under 12 months of age. While cART may control HIV-1 replication to the point that plasma HIV-1 RNA levels are Cetrimonium Bromide(CTAB) undetectable by routine and ultrasensitive assays, HIV-1 DNA remains detectable in circulating CD4+ T cells. The observation that most children, including those with stable, long-term suppression of HIV-1 replication on cART, experience a rebound in viral replication within weeks of discontinuing therapy [6, 7] is compatible with the notion that at least some of the detectable Cetrimonium Bromide(CTAB) cell-associated HIV-1 DNA is usually replication-competent; long-lived memory CD4+ T cells that harbor replication-competent HIV-1 (latent reservoir) serve as a barrier to remedy [8, 9]. Low circulating levels of HIV-1 DNA and smaller latent reservoir size have been measured in adults who have persistently controlled HIV-1 replication off cART following treatment in main contamination [10, 11]. PBMC HIV-1 DNA levels can be readily measured using the small blood volumes available from infants while viral outgrowth assays that measure the portion of replication-competent HIV-1 require relatively large blood volumes (Examined in [8]). Cross-sectional studies have exhibited lower levels of circulating HIV-1 DNA in children who suppressed HIV-1 replication prior to one year of age than after one year of age [12C14]. However, 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 associations between circulating PBMC HIV-1 DNA levels to the timing of cART initiation and the duration of viremic exposure over the first 12 months of treatment. Materials and Methods Study Cohort The study cohort included 30 HIV-1 infected children (Table 1), stratified by timing Cetrimonium Bromide(CTAB) of cART initiation (early therapy, 3 months of age, ET; late therapy, 3 months to 2 years, LT), for whom sufficient cryopreserved PBMC were available to measure HIV-1 DNA prior to and after 1 year of cART. Twenty-eight children received cART through an open-label, Phase I/II clinical trial (Pediatric AIDS Clinical Trials Group Protocol, PACTG 356 (“type”:”clinical-trial”,”attrs”:”text”:”NCT00000872″,”term_id”:”NCT00000872″NCT00000872, [6]) and two were treated by open prescription. HIV-1 DNA levels were measured yearly thereafter up to 4 years following cART initiation in 21 children who achieved plasma HIV-1 RNA levels of 400 copies/ml by 48 weeks of therapy and who sustained plasma HIV-1 RNA 50 copies/ml thereafter (virologic responders). Children were excluded from analyses when plasma HIV-1 RNA was again detected at levels 50 copies/ml. Institutional Review Boards Cetrimonium Bromide(CTAB) at the University or college of Massachusetts Medical School and at the clinical sites participating in PACTG 356 approved this study. Signed informed consent was obtained from Rabbit Polyclonal to SNX3 all study participants guardians. Table 1 Study Cohort: Pre-therapy Viral.