HIV-1 viral load and CD4 cell count in untreated children with vertically acquired asymptomatic or mild disease.

Background: Plasma HIV-1 RNA levels are high in vertically infected infants. Information in older children is limited, particularly in those who have not received antiretroviral therapy. Objectives: To describe the relationships between HIV-1 RNA, age and CD4 cell count in untreated vertically infected children. Design: HIV-1 RNA was measured in 70 children [median age, 3.5 years (range, 0.4-11.9 years); median CD4 cell count, 881 x 10(6)/l (interquartile range, 576-1347 x 10(6) cells/l)] enrolled in a randomized placebo-controlled trial comparing immediate with deferred zidovudine in asymptomatic or mildly symptomatic vertically infected children (PENTA-1 trial). Short-term variability was assessed by comparing HIV-1 RNA at -2 and 0 weeks (prior to randomization). The relationship between age and HIV-1 RNA, and CD4 cell count was analysed using data from all children prior to randomization and sequential samples from 35 remaining on placebo for up to 105 weeks, by fitting mixed linear models. Results: The within-individual SD in viral load was 0.26 log(10) copies/ml. The median plasma HIV-1 RNA at enrolment was 4.61 log(10) (range, 2.3-6.56 log(10) copies/ml), significantly higher in children aged less than or equal to 2 years (median, 5.23 log(10) copies/ml) than in those aged > 2 years (4.51 log(10) copies/ml; P < 0.0001). Mean HIV-1 RNA fell by 0.38 log(10) copies/ml per year up to 2 years of age, by 0.21 log(10) copies/ml per year from 2 to 4 years of age, and by 0.03 log(10) copies/ml per year from 4 to 6 years of age reaching a nadir of 4.25 log(10) copies/ml at 6 years. Mean log(10) CD4 cell count declined steadily with age and was not significantly correlated with HIV-1 RNA, although there was some evidence that the rate of log(10) CD4 cell decline was negatively correlated with the initial rate of HIV-1 RNA decline. No mutations associated with resistance to zidovudine were observed. Conclusions: Age is a key factor in the interpretation of both viral load and CD4 cell count in vertically infected children

Author Correction: Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing.

Risk for late-onset Alzheimer's disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94,437 individuals). We confirm 20 previous LOAD risk loci and identify five new genome-wide loci (IQCK, ACE, ADAM10, ADAMTS1, and WWOX), two of which (ADAM10, ACE) were identified in a recent genome-wide association (GWAS)-by-familial-proxy of Alzheimer's or dementia. Fine-mapping of the human leukocyte antigen (HLA) region confirms the neurological and immune-mediated disease haplotype HLA-DR15 as a risk factor for LOAD. Pathway analysis implicates immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein (APP) metabolism, showing that genetic variants affecting APP and Aβ processing are associated not only with early-onset autosomal dominant Alzheimer's disease but also with LOAD. Analyses of risk genes and pathways show enrichment for rare variants (P = 1.32 × 10-7), indicating that additional rare variants remain to be identified. We also identify important genetic correlations between LOAD and traits such as family history of dementia and education

Author Correction: Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Genetic meta-analysis of diagnosed Alzheimer's disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing.

Risk for late-onset Alzheimer's disease (LOAD), the most prevalent dementia, is partially driven by genetics. To identify LOAD risk loci, we performed a large genome-wide association meta-analysis of clinically diagnosed LOAD (94,437 individuals). We confirm 20 previous LOAD risk loci and identify five new genome-wide loci (IQCK, ACE, ADAM10, ADAMTS1, and WWOX), two of which (ADAM10, ACE) were identified in a recent genome-wide association (GWAS)-by-familial-proxy of Alzheimer's or dementia. Fine-mapping of the human leukocyte antigen (HLA) region confirms the neurological and immune-mediated disease haplotype HLA-DR15 as a risk factor for LOAD. Pathway analysis implicates immunity, lipid metabolism, tau binding proteins, and amyloid precursor protein (APP) metabolism, showing that genetic variants affecting APP and Aβ processing are associated not only with early-onset autosomal dominant Alzheimer's disease but also with LOAD. Analyses of risk genes and pathways show enrichment for rare variants (P = 1.32 × 10-7), indicating that additional rare variants remain to be identified. We also identify important genetic correlations between LOAD and traits such as family history of dementia and education

Author Correction: Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing (Nature Genetics, (2019), 51, 3, (414-430), 10.1038/s41588-019-0358-2)

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Author Correction: Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing (Nature Genetics, (2019), 51, 3, (414-430), 10.1038/s41588-019-0358-2)

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Author Correction: Genetic meta-analysis of diagnosed Alzheimer\u2019s disease identifies new risk loci and implicates A\u3b2, tau, immunity and lipid processing (Nature Genetics, (2019), 51, 3, (414-430), 10.1038/s41588-019-0358-2)

An amendment to this paper has been published and can be accessed via a link at the top of the paper