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      Anthropometric Improvement among HIV Infected Pre-School Children Following Initiation of First Line Anti-Retroviral Therapy: Implications for Follow Up

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          Abstract

          Background

          Antiretroviral therapy (ART) is a lifesaving intervention for HIV infected children. There is a scarcity of data on immunological recovery and its relation with growth indicators among HIV infected young children. The current study aims to assess the pattern of anthropometric Z-score improvement following initiation of first-line ART among under-five children and the relationship between anthropometric Z-score improvement and immunologic recovery.

          Methods

          We included under-five children who were on first-line ART at five major hospitals in Addis Ababa, Ethiopia. We measured anthropometry and collected clinical and laboratory data at follow up, and we retrieved clinical and anthropometric data at ART initiation from records. Z-scores for each of the anthropometric indices were calculated based on WHO growth standards using ENA for SMART 2011 software. Linear regression was used to assess the relationship between time on ART and anthropometric Z-score improvement; and the relationship between anthropometric Z-score improvement and immunologic recovery. Multiple linear regression was used to assess the independent predictors of anthropometric Z-score change.

          Results

          The median age of the participants was 4.1 (Interquartile range (IQR): 3.3–4.9) years. More than half (52.48%) were female. The median duration of follow up was 1.69 (IQR: 1.08–2.63) years. There was a significant improvement in all anthropometric indices at any follow up after initiation of first-line ART (underweight; 39.5% vs16.5%, stunting; 71.3% vs 62.9% and wasting; 16.3% vs 1.0%; p-value< 0.0001). There was an inverse relationship between improvement in weight for age Z-score (WAZ) and duration of ART (R 2 = 0.04; F (1, 158); p = 0.013). Height for age Z-score (HAZ) both at the time of ART initiation and follow up has a positive linear relationship with CD4 percentage at follow up (Coef. = 1.92; R 2 = 0.05; p-value = 0.002). Duration on ART ( Std. Err. = 0.206, t = -1.99, p-value = 0.049) and level of maternal education ( Std. Err. = 0.290, t = 2.64, p-value = 0.009) were the only independent predictors of the change in WAZ and change in HAZ at any follow up visit respectively.

          Conclusion

          There was a significant improvement in all anthropometric indices at any follow-up after initiation of first-line ART among under-five children. HAZ was linearly related with immunologic recovery following ART initiation. The findings indicate that anthropometric indices could be taken as proxy indicators of immunologic recovery for under-five children.

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          Most cited references23

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          The interaction between nutrition and infection.

          Infection and malnutrition have always been intricately linked. Malnutrition is the primary cause of immunodeficiency worldwide, and we are learning more and more about the pathogenesis of this interaction. Five infectious diseases account for more than one-half of all deaths in children aged <5 years, most of whom are undernourished. Micronutrient deficiencies have effects such as poor growth, impaired intellect, and increased mortality and susceptibility to infection. The worldwide magnitude of parasite infection is enormous. It is understood that parasites may lead to malnutrition, but the extent to which malnutrition causes increased parasite infestation is not known; thus, the conditions need to be addressed together. Nutritional deficiencies associated with pregnancy are associated with poor immune response to infection. Because this immune deficiency is partially compensated by breast-feeding, this is the single best way to protect infants from infection. Malnutrition and nutritional alterations, common complications of human immunodeficiency virus infection, include disorders of food intake, nutrient absorption, and intermediary metabolism and play a significant and independent role in morbidity and mortality. The 21st century provides new information and new challenges. With new technologies and political changes, it is hoped that a healthier, more disease-free, and better-nourished population will emerge.
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            The impact of malnutrition on survival and the CD4 count response in HIV-infected patients starting antiretroviral therapy.

            The impact that malnutrition at the time of starting antiretroviral therapy (ART) has on survival and the CD4 count response is not known. A retrospective cohort study of patients attending the national HIV referral centre in Singapore who had a CD4 count less than 250 cells/microL and a measurement of body weight performed at the time of starting ART was carried out. Demographic and clinical variables were extracted from an existing database. Body mass index (BMI) was calculated from the weight in kilograms divided by the square of the height in metres. Moderate to severe malnutrition was defined as BMI less than 17 kg/m(2). Intent-to-treat Cox models were used to determine the predictors of survival. A total of 394 patients were included in the analysis, of whom 79 died during a median study follow-up of 2.4 years. Moderate to severe malnutrition was present in 16% of patients at the time of starting ART, and was found to be a significant independent predictor of death [hazard ratio (HR) 2.19, 95% confidence interval (CI) 1.29-3.73, P=0.004 for those with BMI 18.5] as were stage of disease (HR 2.47, 95% CI 1.20-5.07, P=0.014 for those who were at stage C compared with those at stage A) and the type of ART [HR 0.50, 95% CI 0.27-0.93, P=0.03 for highly active antiretroviral therapy (HAART) compared with non-HAART treatment]. Malnutrition did not impair the magnitude of the increase in CD4 count at 6 or 12 months. Malnutrition at the time of starting ART was significantly associated with decreased survival, but the effect appeared not to be mediated by impaired immune reconstitution. Given the increasing access to ART in developing countries and the high frequency of HIV-associated wasting, studies of nutritional therapy as an adjunct to the initiation of HAART are urgently needed.
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              Energy expenditure in HIV infection.

              Energy intake recommendations for adults should be based preferably on direct measurements of total daily energy expenditure (TDEE) in corresponding populations who are maintaining healthy body weight and satisfactory physical activity levels. During adolescence, pregnancy, and lactation, energy requirements should be based on TDEE plus the additional energy required to advance these physiologic states. With illness, energy expenditure and energy intake change, but nutritional intervention is not necessarily beneficial. This article reviews data on energy expenditure in HIV infection with a focus on adults, adolescents aged ≥14 y, and pregnant and lactating women. Resting energy expenditure (REE) in adults with untreated asymptomatic HIV is ~ 10% higher than in healthy control subjects. In asymptomatic adults receiving antiretroviral therapy, REE may be similarly increased. HIV wasting and secondary infections are also associated with increased REE. In contrast, TDEE is typically normal in asymptomatic HIV and decreased in HIV wasting and secondary infection. No direct measurements of REE or TDEE are available in adolescents or in pregnant or lactating women with HIV. On the basis of current data, energy intake may need to increase by ~ 10% in adults with asymptomatic HIV to maintain body weight. In adolescents and in pregnant and lactating women with asymptomatic HIV, energy requirements should approximate recommendations for their uninfected counterparts until further data are available. In the resource-rich world, the energy expenditure changes associated with HIV are unlikely to contribute to significant weight loss. More data are needed on energy expenditure in HIV-infected populations from developing nations, where concurrent malnutrition and coinfections are common.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                28 December 2016
                2016
                : 11
                : 12
                : e0167565
                Affiliations
                [1 ]St Paul’s Hospital Millennium Medical College, Addis Ababa, Ethiopia
                [2 ]Hawassa University, Department of Pediatrics, Hawassa, Ethiopia
                [3 ]Addis Ababa University, School of Medicine, Addis Ababa, Ethiopia
                [4 ]ALERT Medical Center, Addis Ababa, Ethiopia
                UNAIDS, GUYANA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: AMT BTT.

                • Data curation: AMT BTT.

                • Formal analysis: BTT AMT.

                • Investigation: AMT AZG DS MG.

                • Methodology: AMT BTT.

                • Project administration: AMT MG DS AZG.

                • Resources: AMT BTT AZG DS MG.

                • Software: BTT AMT.

                • Supervision: AMT DS AZG MG.

                • Validation: AMT BTT DS MG AZG.

                • Visualization: BTT AMT.

                • Writing – original draft: BTT AMT.

                • Writing – review & editing: BTT AMT MG DS AZG.

                Author information
                http://orcid.org/0000-0003-4005-8605
                Article
                PONE-D-16-15483
                10.1371/journal.pone.0167565
                5193336
                28030557
                9438d9c2-1a88-4971-b0b5-1d9589883584
                © 2016 Tekleab et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 17 April 2016
                : 16 November 2016
                Page count
                Figures: 4, Tables: 5, Pages: 14
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                Social Sciences
                Anthropology
                Physical Anthropology
                Anthropometry
                Biology and Life Sciences
                Physical Anthropology
                Anthropometry
                Medicine and health sciences
                Infectious diseases
                Viral diseases
                HIV infections
                People and Places
                Population Groupings
                Age Groups
                Children
                People and Places
                Population Groupings
                Families
                Children
                Biology and Life Sciences
                Nutrition
                Malnutrition
                Medicine and Health Sciences
                Nutrition
                Malnutrition
                Medicine and Health Sciences
                Pediatrics
                Pediatric Infections
                Medicine and health sciences
                Diagnostic medicine
                HIV diagnosis and management
                Biology and Life Sciences
                Immunology
                Vaccination and Immunization
                Antiviral Therapy
                Antiretroviral Therapy
                Medicine and Health Sciences
                Immunology
                Vaccination and Immunization
                Antiviral Therapy
                Antiretroviral Therapy
                Medicine and Health Sciences
                Public and Occupational Health
                Preventive Medicine
                Vaccination and Immunization
                Antiviral Therapy
                Antiretroviral Therapy
                Research and Analysis Methods
                Mathematical and Statistical Techniques
                Statistical Methods
                Regression Analysis
                Linear Regression Analysis
                Physical Sciences
                Mathematics
                Statistics (Mathematics)
                Statistical Methods
                Regression Analysis
                Linear Regression Analysis
                Custom metadata
                Due to concerns related to participant confidentiality, the data are available upon request. Interested researchers may contact Dr Birkneh Tilahun Tadesse at: birknehtilahun@ 123456gmail.com , or Dr Atnafu Mekonnen Tekleab at: atnemekonnen@ 123456yahoo.com .

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