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      Anemia and Red Blood Cell Abnormalities in HIV-Infected and HIV-Exposed Breastfed Infants: A Secondary Analysis of the Kisumu Breastfeeding Study

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          Abstract

          Background

          Anemia results in increased morbidity and mortality, underscoring the need to better understand its pathophysiology amongst HIV-exposed and infected children in sub-Saharan Africa, the region where most infant HIV exposure and infections occur.

          Methods

          This analysis used samples obtained from children in the Kisumu Breastfeeding Study (KiBS). KiBS was a longitudinal phase IIB, open-label, one-arm clinical trial, designed to investigate the safety, tolerability and effectiveness of a maternal triple-antiretroviral (ARV) regimen for prevention of mother-to-child transmission (PMTCT) of HIV, during late pregnancy and early infancy while breastfeeding. Blood samples from 482 children were obtained at birth, 2, 6, 10 and 14 weeks and 6, 9, 12, 18 and 24 months. Severity of anemia was graded using the NIH Division of AIDS (DAIDS) toxicity tables. We describe the proportion of children with anemia and anomalies in red blood cell parameters at various time points over 24 months and compare rates of anemia between HIV-infected and HIV-uninfected children and by mothers’ ARV regimen and infant malaria infection.

          Results

          The proportion of children with anemia significantly increased after the breastfeeding period in both HIV-infected and HIV-uninfected children with higher proportion among HIV-infected children compared to HIV-uninfected children (RR: 1.72; CI: 1.22–2.44, p = 0.002). Maternal triple-antiretroviral regimen was not associated with infant anemia (p = 0.11). There was no significant difference in mean hemoglobin between HIV-uninfected children with and without malaria at each time point except at 24 months.

          Conclusion

          A relatively lower proportion of children with severe anemia during the breastfeeding period suggest that exposure to mother’s triple antiretroviral combinations through breast milk, posed minimal risk of hematologic toxicity.

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          Most cited references31

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          Binomial regression in GLIM: estimating risk ratios and risk differences.

          Although an estimate of the odds ratio adjusted for other covariates can be obtained by logistic regression, until now there has been no simple way to estimate other interesting parameters such as the risk ratio and risk difference multivariately for prospective binomial data. These parameters can be estimated in the generalized linear model framework by choosing different link functions or transformations of binomial or binary data. Macros for use with the program GLIM provide a simple method to compute parameters other than the odds ratio while adjusting for confounding factors. A data set presented previously is used as an example.
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            Effect of co-trimoxazole prophylaxis, antiretroviral therapy, and insecticide-treated bednets on the frequency of malaria in HIV-1-infected adults in Uganda: a prospective cohort study.

            HIV-1 and malaria are common infections in Africa, and cause substantial morbidity and mortality. HIV infection has been associated with an increased incidence of malaria, and more severe disease. Our aim was to assess the effect of antiretroviral treatment (ART) on the frequency of clinical malaria in people with HIV, and to measure the additive effects of co-trimoxazole (trimethoprim and sulfamethoxazole) prophylaxis, ART, and insecticide-treated bednets. In 2001, we enrolled 466 HIV-infected individuals aged 18 years or older in Uganda in a prospective cohort study that provided co-trimoxazole prophylaxis to 399 participants after 5 months of no intervention. In 2003, we enrolled 138 survivors from the initial study, and 897 new participants from the same community, to take antiretroviral therapy (ART) in addition to co-trimoxazole prophylaxis. The ART was in most cases a combination of stavudine, lamivudine, and nevirapine or efavirenz. In 2004, we also gave participants insecticide-treated bednets. Households were visited weekly by study staff to record fever, illness, or death in the preceding 7 days. In cases of reported fever in the previous 2 days, we took blood to test for malaria parasites. We compared the frequency of clinical malaria, adjusting for CD4-cell count, age, sex, and season. 1035 individuals were given co-trimoxazole and ART (median age 38 years, 74% female, and median CD4-cell count 124 cells/microL); 985 of these, plus four new participants, received co-trimoxazole, ART, and bednets. There were 166 cases of clinical malaria in the study. Compared with a baseline malaria incidence of 50.8 episodes per 100 person-years, co-trimoxazole prophylaxis was associated with 9.0 episodes per 100 person-years (adjusted incidence rate ratio [IRR] 0.24, 95% CI 0.15-0.38); ART and co-trimoxazole with 3.5 episodes per 100 person-years (0.08, 0.04-0.17); and co-trimoxazole, ART, and bednets with 2.1 episodes per 100 person-years (0.05, 0.03-0.08). Malaria incidence was significantly lower during ART and co-trimoxazole than during co-trimoxazole alone (IRR 0.36 [95% CI 0.18-0.74], p=0.0056). A combination of co-trimoxazole, antiretroviral therapy, and insecticide-treated bednets substantially reduced the frequency of malaria in adults with HIV.
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              Blood transfusion for severe anaemia in children in a Kenyan hospital.

              Severe anaemia often secondary to malaria is a major contributor to child mortality in sub-Saharan Africa. We have confirmed that use of simple clinical and laboratory criteria can identify those children likely to benefit most from treatment. We have also shown that the speed of response may be critical. The quality and capacity of blood transfusion services could therefore have a major, direct effect on inpatient child mortality.
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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
                3 November 2015
                2015
                : 10
                : 11
                : e0141599
                Affiliations
                [1 ]Centre for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya
                [2 ]Division of HIV/AIDS Prevention, U.S. Centers for Disease Control and Prevention (CDC), Kisumu, Kenya
                [3 ]Center for Poverty-related Communicable Diseases, Department of Internal Medicine, Center for Infection and Immunity, Amsterdam Institute for Global Health and Development, University of Amsterdam, Amsterdam, Netherlands
                [4 ]Jaramogi Oginga Odinga Teaching and Referral Hospital, Kisumu, Kenya
                [5 ]Family Health International, Nairobi, Kenya
                [6 ]Division of HIV/AIDS Prevention, National Center for HIV, Viral Hepatitis, STD, and TB Prevention, CDC, Atlanta, GA, United States of America
                University of Pittsburgh Center for Vaccine Research, UNITED STATES
                Author notes

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

                Conceived and designed the experiments: TT CZ RM PW. Performed the experiments: BA P. Omolo HL. Analyzed the data: CO JW TT CZ PW P. Ondoa. Contributed reagents/materials/analysis tools: JO JW P. Ondoa. Wrote the paper: CO CZ TT PW JW P. Ondoa. Reviewed the manuscript: CO CZ P. Ondoa P. Omolo BA HL RL JW JO RM PW TT.

                [¤]

                Current address: U.S. Centers for Disease Control and Prevention (CDC), Addis Ababa, Ethiopia

                ¶ Membership of the KiBS Study Team is listed in the Acknowledgments.

                Article
                PONE-D-15-26717
                10.1371/journal.pone.0141599
                4631368
                26529316
                0614b30d-ec39-4d96-8103-855d8af6c11c

                This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication

                History
                : 18 June 2015
                : 9 October 2015
                Page count
                Figures: 3, Tables: 2, Pages: 14
                Funding
                This study received funding from the Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, Georgia, USA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Custom metadata
                All relevant data are within the paper.

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