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      Absence of neurocognitive disadvantage associated with paediatric HIV subtype A infection in children on antiretroviral therapy

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          Abstract

          Introduction

          Infection with HIV subtype A has been associated with poorer neurocognitive outcomes compared to HIV subtype D in Ugandan children not eligible for antiretroviral therapy ( ART). In this study, we sought to determine whether subtype‐specific differences are also observed among children receiving ART.

          Materials and Methods

          Children were recruited from a clinical trial in which they were randomized to receive either lopinavir ( LPV)‐ or non‐nucleoside reverse transcriptase inhibitor ( NNRTI)‐ based ART (NCT00978068). Age at initiation of ART ranged from six months to six years. HIV subtype was determined by PCR amplification and population sequencing of the pol region derived from peripheral blood mononuclear cell DNA, followed by application of the REGA and Recombinant Identification Programme algorithms. General cognition was assessed using the Kaufman Assessment Battery for Children (Second Edition), attention using the Test of Variables of Attention, and motor skills using the Bruininks‐Oseretsky Test of Motor Proficiency (Second Edition). Home environment was assessed using the Home Observation for the Measurement of the Environment ( HOME). Age‐adjusted test z‐scores were entered into a regression model that adjusted for sex, socio‐economic status score, HOME score, years of schooling, and ART treatment type.

          Results

          One hundred and five children were tested; median (interquartile range) age was 7.05 years (6.30 to 8.44), CD4 count was 867.7 cells/mm 3 (416.0 to 1203.5), and duration on ART was 4.03 years (3.55 to 4.23). Seventy‐eight children had HIV subtype A and 27 had subtype D; the groups had comparable home and socio‐economic status, except that there were more males among children infected with subtype A than D (64.7% vs. 35.3%, p = 0.02). There were no differences between the subtypes in general cognition (estimated mean difference: 0.20; 95% CI: −0.11 to 0.50); p = 0.21), attention (−0.18, 95% CI: −0.60 to 0.24, p = 0.41) and motor skills (1.60, 95% CI: −0.84 to 4.04, p = 0.20).

          Conclusions

          Our results imply that ART may diminish the neurocognitive disadvantage seen in treatment‐naïve HIV‐infected children with subtype A.

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          Most cited references31

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          Methods to explain the clinical significance of health status measures.

          One can classify ways to establish the interpretability of quality-of-life measures as anchor based or distribution based. Anchor-based measures require an independent standard or anchor that is itself interpretable and at least moderately correlated with the instrument being explored. One can further classify anchor-based approaches into population-focused and individual-focused measures. Population-focused approaches are analogous to construct validation and rely on multiple anchors that frame an individual's response in terms of the entire population (eg, a group of patients with a score of 40 has a mortality of 20%). Anchors for population-based approaches include status on a single item, diagnosis, symptoms, disease severity, and response to treatment. Individual-focused approaches are analogous to criterion validation. These methods, which rely on a single anchor and establish a minimum important difference in change in score, require 2 steps. The first step establishes the smallest change in score that patients consider, on average, to be important (the minimum important difference). The second step estimates the proportion of patients who have achieved that minimum important difference. Anchors for the individual-focused approach include global ratings of change within patients and global ratings of differences between patients. Distribution-based methods rely on expressing an effect in terms of the underlying distribution of results. Investigators may express effects in terms of between-person standard deviation units, within-person standard deviation units, and the standard error of measurement. No single approach to interpretability is perfect. Use of multiple strategies is likely to enhance the interpretability of any particular instrument.
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            A computer program designed to screen rapidly for HIV type 1 intersubtype recombinant sequences.

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                Author and article information

                Contributors
                pbangirana@yahoo.com
                Journal
                J Int AIDS Soc
                J Int AIDS Soc
                10.1002/(ISSN)1758-2652
                JIA2
                Journal of the International AIDS Society
                John Wiley and Sons Inc. (Hoboken )
                1758-2652
                20 October 2017
                October 2017
                : 20
                : 2 ( doiID: 10.1111/jia2.2017.20.issue-2 )
                : e25015
                Affiliations
                [ 1 ] Department of Psychiatry Makerere University College of Health Sciences Kampala Uganda
                [ 2 ] Department of Pediatrics University of California San Francisco CA USA
                [ 3 ] Department of Psychiatry Michigan State University East Lansing MI USA
                [ 4 ] Blood Systems Research Institute San Francisco CA USA
                [ 5 ] Department of Laboratory Medicine University of California San Francisco CA USA
                [ 6 ] Federal University of São Paulo São Paulo Brazil
                [ 7 ] Department of Statistics and Probability Michigan State University East Lansing MI USA
                [ 8 ] Disease Control and Elimination Theme Medical Research Council Unit Banjul The Gambia
                Author notes
                [*] [* ]Corresponding author: Paul Bangirana, Makerere University, Department of Psychiatry, Upper Mulago Hill Road, Box 7072, Kampala, Uganda. Tel: +256 772 673831. ( pbangirana@ 123456yahoo.com )
                Author information
                http://orcid.org/0000-0002-7136-0594
                Article
                JIA225015
                10.1002/jia2.25015
                5810341
                29052340
                507059ab-6fe8-4ea7-b3f3-3e62055fc926
                © 2017 The Authors. Journal of the International AIDS Society published by John Wiley & sons Ltd on behalf of the International AIDS Society.

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 11 April 2017
                : 28 September 2017
                Page count
                Figures: 0, Tables: 4, Pages: 6, Words: 5372
                Funding
                Funded by: International AIDS Society
                Funded by: National Institutes of Health
                Award ID: R01HD070723
                Categories
                Short Report
                Short Reports
                Custom metadata
                2.0
                jia225015
                October 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.3.2.2 mode:remove_FC converted:13.02.2018

                Infectious disease & Microbiology
                hiv subtype,neurocognition,children,antiretroviral therapy
                Infectious disease & Microbiology
                hiv subtype, neurocognition, children, antiretroviral therapy

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