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      Targeted HIV testing at birth supported by low and predictable mother‐to‐child transmission risk in Botswana

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          Abstract

          Introduction

          Most African countries perform infant HIV testing at 6 weeks or later. The addition of targeted testing at birth may improve retention in care, treatment outcomes and survival for HIV‐infected infants.

          Methods

          HIV‐exposed infants were screened as part of the Early Infant Treatment ( EIT) study in Botswana. Screened infants were ≥35 weeks gestational age and ≥2000 g at birth. Risk factors for mother‐to‐child transmission ( MTCT) were assessed by maternal obstetric card or verbally. Risk factors included <8 weeks ART in pregnancy, last known CD4 <250 cells/mm 3, last known HIV RNA >400 copies/mL, poor maternal ART adherence, lack of maternal zidovudine ( ZDV) in labour, or lack of infant post‐exposure prophylaxis. Infants underwent dried blood spot testing by Roche Cobas Ampliprep/Cobas Taqman HIV‐1 qualitative PCR.

          Results

          From April 2015 to April 2016, 2303 HIV‐exposed infants were tested for HIV in the EIT study. Of these, 369 (16%) were identified as high risk for HIV infection by information available at birth, and 12 (0.5% overall, 3.25% of high risk) were identified as HIV positive at birth. All 12 positive infants were identified as high risk at the time of screening, and only 2 risk factors were required to identify all positive infants: either <8 weeks of maternal ART in pregnancy (75%) or lack of maternal HIV suppression at last test (25%).

          Conclusions

          In utero MTCT occurred only among infants identified as high risk at delivery, using information available from the mother or obstetric record. Birth testing that targets high‐risk infants based on maternal ART receipt is likely to identify the majority of in utero HIV transmissions, and allows early ART initiation for these infants.

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          Most cited references10

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          Benefits and Risks of Antiretroviral Therapy for Perinatal HIV Prevention.

          Background Randomized-trial data on the risks and benefits of antiretroviral therapy (ART) as compared with zidovudine and single-dose nevirapine to prevent transmission of the human immunodeficiency virus (HIV) in HIV-infected pregnant women with high CD4 counts are lacking. Methods We randomly assigned HIV-infected women at 14 or more weeks of gestation with CD4 counts of at least 350 cells per cubic millimeter to zidovudine and single-dose nevirapine plus a 1-to-2-week postpartum "tail" of tenofovir and emtricitabine (zidovudine alone); zidovudine, lamivudine, and lopinavir-ritonavir (zidovudine-based ART); or tenofovir, emtricitabine, and lopinavir-ritonavir (tenofovir-based ART). The primary outcomes were HIV transmission at 1 week of age in the infant and maternal and infant safety. Results The median CD4 count was 530 cells per cubic millimeter among 3490 primarily black African HIV-infected women enrolled at a median of 26 weeks of gestation (interquartile range, 21 to 30). The rate of transmission was significantly lower with ART than with zidovudine alone (0.5% in the combined ART groups vs. 1.8%; difference, -1.3 percentage points; repeated confidence interval, -2.1 to -0.4). However, the rate of maternal grade 2 to 4 adverse events was significantly higher with zidovudine-based ART than with zidovudine alone (21.1% vs. 17.3%, P=0.008), and the rate of grade 2 to 4 abnormal blood chemical values was higher with tenofovir-based ART than with zidovudine alone (2.9% vs. 0.8%, P=0.03). Adverse events did not differ significantly between the ART groups (P>0.99). A birth weight of less than 2500 g was more frequent with zidovudine-based ART than with zidovudine alone (23.0% vs. 12.0%, P<0.001) and was more frequent with tenofovir-based ART than with zidovudine alone (16.9% vs. 8.9%, P=0.004); preterm delivery before 37 weeks was more frequent with zidovudine-based ART than with zidovudine alone (20.5% vs. 13.1%, P<0.001). Tenofovir-based ART was associated with higher rates than zidovudine-based ART of very preterm delivery before 34 weeks (6.0% vs. 2.6%, P=0.04) and early infant death (4.4% vs. 0.6%, P=0.001), but there were no significant differences between tenofovir-based ART and zidovudine alone (P=0.10 and P=0.43). The rate of HIV-free survival was highest among infants whose mothers received zidovudine-based ART. Conclusions Antenatal ART resulted in significantly lower rates of early HIV transmission than zidovudine alone but a higher risk of adverse maternal and neonatal outcomes. (Funded by the National Institutes of Health; PROMISE ClinicalTrials.gov numbers, NCT01061151 and NCT01253538 .).
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            HIV type 1 (HIV-1) proviral reservoirs decay continuously under sustained virologic control in HIV-1-infected children who received early treatment.

            Early initiation of combination antiretroviral therapy (cART) to human immunodeficiency virus type 1 (HIV-1)-infected infants controls HIV-1 replication and reduces mortality. Plasma viremia (lower limit of detection, <2 copies/mL), T-cell activation, HIV-1-specific immune responses, and the persistence of cells carrying replication-competent virus were quantified during long-term effective combination antiretroviral therapy (cART) in 4 perinatally HIV-1-infected youth who received treatment early (the ET group) and 4 who received treatment late (the LT group). Decay in peripheral blood mononuclear cell (PBMC) proviral DNA levels was also measured over time in the ET youth. Plasma viremia was not detected in any ET youth but was detected in all LT youth (median, 8 copies/mL; P = .03). PBMC proviral load was significantly lower in ET youth (median, 7 copies per million PBMCs) than in LT youth (median, 181 copies; P = .03). Replication-competent virus was recovered from all LT youth but only 1 ET youth. Decay in proviral DNA was noted in all 4 ET youth in association with limited T-cell activation and with absent to minimal HIV-1-specific immune responses. Initiation of early effective cART during infancy significantly limits circulating levels of proviral and replication-competent HIV-1 and promotes continuous decay of viral reservoirs. Continued cART with reduction in HIV-1 reservoirs over time may facilitate HIV-1 eradication strategies. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
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              Paediatric HIV infection: the potential for cure.

              Recent anecdotal reports of HIV-infected children who received early antiretroviral therapy (ART) and showed sustained control of viral replication even after ART discontinuation have raised the question of whether there is greater intrinsic potential for HIV remission, or even eradication ('cure'), in paediatric infection than in adult infection. This Review describes the influence of early initiation of ART, of immune ontogeny and of maternal factors on the potential for HIV cure in children and discusses the unique immunotherapeutic opportunities and obstacles that paediatric infection may present.
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                Author and article information

                Contributors
                rshapiro@hsph.harvard.edu
                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
                May 2018
                29 May 2018
                : 21
                : 5 ( doiID: 10.1002/jia2.2018.21.issue-5 )
                : e25111
                Affiliations
                [ 1 ] Harvard Medical School Doris Duke International Clinical Research Fellowship Boston MA USA
                [ 2 ] University of California Los Angeles David Geffen School of Medicine Los Angeles CA USA
                [ 3 ] Botswana Harvard AIDS Institute Partnership Gaborone Botswana
                [ 4 ] Department of Biostatistics Harvard T.H Chan School of Public Health Boston MA USA
                [ 5 ] Department of Immunology and Infectious Diseases Harvard T.H Chan School of Public Health Boston MA USA
                [ 6 ] Infectious Disease Division Brigham and Women's Hospital Boston MA USA
                [ 7 ] National Institute of Allergy and Infectious Diseases National Institutes of Health Bethesda MD USA
                [ 8 ] Infectious Disease Division Massachusetts General Hospital Boston MA USA
                Author notes
                [*] [* ] Corresponding author: Roger L Shapiro, Department of Immunology and Infectious Diseases, Harvard T.H Chan School of Public Health, Boston, MA, USA. Tel: 617 432 7264. ( rshapiro@ 123456hsph.harvard.edu ).
                Author information
                http://orcid.org/0000-0003-3517-6543
                Article
                JIA225111
                10.1002/jia2.25111
                5980617
                29852062
                3f18c7fc-1ecf-4526-ba6f-9f28b4cb44f3
                © 2018 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 http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 30 November 2017
                : 16 April 2018
                Page count
                Figures: 1, Tables: 3, Pages: 20, Words: 4913
                Funding
                Funded by: National Institutes of Health
                Funded by: Doris Duke Foundation
                Categories
                Research Article
                Research Articles
                Custom metadata
                2.0
                jia225111
                May 2018
                Converter:WILEY_ML3GV2_TO_NLMPMC version:version=5.4.0 mode:remove_FC converted:31.05.2018

                Infectious disease & Microbiology
                hiv,mother‐to‐child transmission,children,paediatrics,vertical transmission,viral suppression

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