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HIV-exposed uninfected

Jennifer Jao, Rohan Hazra, Claude A Mellins, Robert H Remien, Elaine J Abrams
INTRODUCTION: The tremendous success of antiretroviral therapy has resulted in a diminishing population of perinatally HIV-infected children on the one hand and a mounting number of HIV-exposed uninfected (HEU) children on the other. As the oldest of these HEU children are reaching adolescence, questions have emerged surrounding the implications of HEU status disclosure to these adolescents. This article outlines the arguments for and against disclosure of a child's HEU status. DISCUSSION: Disclosure of a child's HEU status, by definition, requires disclosure of maternal HIV status...
2016: Journal of the International AIDS Society
Bahaa Abu-Raya, Tobias R Kollmann, Arnaud Marchant, Duncan M MacGillivray
Infants born to human immunodeficiency virus (HIV) infected women are HIV-exposed but the majority remains uninfected [i.e., HIV-exposed uninfected (HEU)]. HEU infants suffer greater morbidity and mortality from infections compared to HIV-unexposed (HU) peers. The reason(s) for these worse outcomes are uncertain, but could be related to an altered immune system state. This review comprehensively summarizes the current literature investigating the adaptive and innate immune system of HEU infants. HEU infants have altered cell-mediated immunity, including impaired T-cell maturation with documented hypo- as well as hyper-responsiveness to T-cell activation...
2016: Frontiers in Immunology
Vanessa M Oddo, Parul Christian, Joanne Katz, Li Liu, Naoko Kozuki, Robert E Black, Robert Ntozini, Jean Humphrey
BACKGROUND: In sub-Saharan Africa, one-third of all births are small for gestational age (SGA), and 4.4 million children are stunted; both conditions increase the risk of child mortality. SGA has also been shown to increase the risk of stunting. OBJECTIVE: We tested whether the association between SGA and postneonatal mortality is mediated by stunting. METHODS: We used longitudinal data from children aged 6 wk to 24 mo (n = 12,155) enrolled in the ZVITAMBO (Zimbabwe Vitamin A for Mothers and Babies) trial...
October 12, 2016: Journal of Nutrition
K J Alcock, Amina Abubakar, Charles R Newton, Penny Holding
BACKGROUND: HIV infection has been associated with impaired language development in prenatally exposed children. Although most of the burden of HIV occurs in sub-Saharan Africa, there have not been any comprehensive studies of HIV exposure on multiple aspects of language development using instruments appropriate for the population. METHODS: We compared language development in children exposed to HIV in utero to community controls (N = 262, 8-30 months) in rural Kenya, using locally adapted and validated communicative development inventories...
October 12, 2016: BMC Research Notes
Sophie Desmonde, Tessa Goetghebuer, Claire Thorne, Valériane Leroy
PURPOSE OF REVIEW: The number of HIV-exposed but uninfected (HEU) infants exposed to both HIV and multiple antiretroviral drugs in utero and during prolonged breastfeeding is increasing in low-income countries where HIV prevalence is the highest. We review recent evidence on the effects of perinatal/postnatal exposure to maternal HIV and combined antiretroviral therapy (cART) on health outcomes of HEU children (mitochondrial and metabolic toxicity, adverse pregnancy outcomes, neurodevelopment, growth, infectious morbidity, and mortality)...
September 2016: Current Opinion in HIV and AIDS
Kenneth K Mugwanya, Craig W Hendrix, Nelly R Mugo, Mark Marzinke, Elly T Katabira, Kenneth Ngure, Nulu B Semiyaga, Grace John-Stewart, Timothy R Muwonge, Gabriel Muthuri, Andy Stergachis, Connie L Celum, Jared M Baeten
BACKGROUND: As pre-exposure prophylaxis (PrEP) becomes more widely used in heterosexual populations, an important consideration is its safety in infants who are breastfed by women taking PrEP. We investigated whether tenofovir and emtricitabine are excreted into breast milk and then absorbed by the breastfeeding infant in clinically significant concentrations when used as PrEP by lactating women. METHODS AND FINDINGS: We conducted a prospective short-term, open-label study of daily oral emtricitabine-tenofovir disoproxil fumarate PrEP among 50 HIV-uninfected breastfeeding African mother-infant pairs between 1-24 wk postpartum (ClinicalTrials...
September 2016: PLoS Medicine
A L Slogrove, L Frigati, D M Gray
With improved prevention of mother to child transmission of HIV, paediatric HIV disease is less common. However, the number of HIV exposed but uninfected infants is growing. Exposure to maternal HIV impacts infant respiratory health through an increase in known risk factors such as increased preterm birth and low birth weight, suboptimal breastfeeding, increased psychosocial stressors and increased exposure to infective pathogens. Exposure to the HIV virus and altered maternal immune environment result in immunologic changes in the infant that may contribute to respiratory disease risk...
August 19, 2016: Paediatric Respiratory Reviews
Myron J Levin, Jane C Lindsey, Susan S Kaplan, Werner Schimana, Jody Lawrence, Monica M McNeal, Mutsa Bwakura-Dangarembizi, Anthony Ogwu, Evans M Mpabalwani, Paul Sato, George Siberry, Margaret Nelson, Darcy Hille, Geoffrey A Weinberg, Adriana Weinberg
OBJECTIVE: Although many HIV-infected (HIV+) and HIV-exposed but uninfected (HEU) infants have received live rotavirus vaccines since the World Health Organization recommended universal administration of these vaccines to infants, there has been limited prospective information on their safety and immunogenicity in either group of infants. DESIGN/METHODS: We performed a randomized, double-blinded, placebo-controlled trial of the safety and immunogenicity of oral pentavalent rotavirus vaccine (RV5) administered to HIV+ and HEU infants in 4 African countries...
September 20, 2016: AIDS
Mira Hleyhel, Stéphanie Goujon, Jeanne Sibiude, Stephane Blanche, Josiane Warszawski
Ethyl methyl sulfone (EMS) contained in nelfinavir between 2007 and 2008 accidentally exposed embryos and fetuses to a powerful mutagen. We report data for 101 HIV-uninfected children exposed in utero included in the French prospective national cohort. The incidence of malformation was similar to that in the cohort as a whole with different drug exposures; no children had developed cancer after 9 years of follow up.
September 20, 2016: AIDS
Tamsen J Rochat, Joanie Mitchell, Alan Stein, Ntombizodumo Brilliant Mkwanazi, Ruth M Bland
Advances in access to HIV prevention and treatment have reduced vertical transmission of HIV, with most children born to HIV-infected parents being HIV-uninfected themselves. A major challenge that HIV-infected parents face is disclosure of their HIV status to their predominantly HIV-uninfected children. Their children enter middle childhood and early adolescence facing many challenges associated with parental illness and hospitalization, often exacerbated by stigma and a lack of access to health education and support...
2016: Frontiers in Public Health
Bahaa Abu-Raya, Kinga K Smolen, Fabienne Willems, Tobias R Kollmann, Arnaud Marchant
The transfer of maternal immune factors to the newborn is critical for protection from infectious disease in early life. Maternally acquired passive immunity provides protection until the infant is beyond early life's increased susceptibility to severe infections or until active immunity is achieved following infant's primary immunization. However, as reviewed here, human immunodeficiency virus (HIV) infection alters the transfer of immune factors from HIV-infected mothers to the HIV-exposed newborns and young infants...
2016: Frontiers in Immunology
Stephen A Spector, Sean S Brummel, Caroline M Nievergelt, Adam X Maihofer, Kumud K Singh, Murli U Purswani, Paige L Williams, Rohan Hazra, Russell Van Dyke, George R Seage
The Pediatric HIV/AIDS Cohort Study (PHACS), the largest ongoing longitudinal study of perinatal HIV-infected (PHIV) and HIV-exposed, uninfected (PHEU) children in the United States, comprises the Surveillance Monitoring of Antiretroviral Therapy [ART] Toxicities (SMARTT) Study in PHEU children and the Adolescent Master Protocol (AMP) that includes PHIV and PHEU children ≥7 years. Although race/ethnicity is often used to assess health outcomes, this approach remains controversial and may fail to accurately reflect the backgrounds of ancestry-diverse populations as represented in the PHACS participants...
September 2016: Medicine (Baltimore)
Rebecca M Zash, Roger L Shapiro, Jean Leidner, Carolyn Wester, Alexander J McAdam, Richard L Hodinka, Ibou Thior, Claire Moffat, Joseph Makhema, Kenneth McIntosh, Max Essex, Shahin Lockman
BACKGROUND: Diarrhoea and pneumonia are common causes of childhood death in sub-Saharan Africa but there are few studies describing specific pathogens. OBJECTIVES: The study aimed to describe the pathogens associated with diarrhoea, pneumonia and oropharyngeal colonization in children born to HIV-infected women (HIV-exposed infants). METHODS: The Mashi Study randomized 1200 HIV-infected women and their infants to breastfeed for 6 months with ZDV prophylaxis or formula-feed with 4 weeks of ZDV...
August 2016: Paediatrics and International Child Health
Candice Ruck, Brian A Reikie, Arnaud Marchant, Tobias R Kollmann, Fatima Kakkar
HIV-exposed uninfected (HEU) infants experience increased overall mortality from infectious causes when compared to HIV-unexposed uninfected (HU) infants. This is the case in both the resource-rich and resource-limited settings. Here, we explore the concept that specific types of infectious diseases that are more common among HEU infants could provide clues as to the potential underlying immunological abnormalities. The most commonly reported infections in HEU vs. HU infants are caused by encapsulated bacteria, suggesting the existence of a less effective humoral (antibody, complement) immune response...
2016: Frontiers in Immunology
Sandra Hernandez, Constanza Moren, Marc Catalán-García, Marta Lopez, Mariona Guitart-Mampel, Oriol Coll, Laura Garcia, Jose Milisenda, Angela Justamante, Josep Maria Gatell, Francesc Cardellach, Eduard Gratacos, Òscar Miro, Gloria Garrabou
To assess the impact of HIV-infection and highly active anti-retroviral treatment in mitochondria and apoptotic activation of caspases during pregnancy and their association with adverse perinatal outcome. Changes of mitochondrial parameters and apoptotic caspase activation in maternal peripheral blood mononuclear cells were compared at first trimester of pregnancy and delivery in 27 HIV-infected and -treated pregnant women versus 24 uninfected pregnant controls. We correlated immunovirological, therapeutic and perinatal outcome with experimental findings: mitochondrial DNA (mtDNA) content, mitochondrial protein synthesis, mitochondrial function and apoptotic caspase activation...
August 30, 2016: Journal of Cellular and Molecular Medicine
Catherine Sabourin-Poirier, Lyvia Fourcade, Josiane Chagnon-Choquet, Annie-Claude Labbé, Michel Alary, Fernand Guédou, Johanne Poudrier, Michel Roger
We have previously shown that excess B lymphocyte Stimulator (BLyS)/BAFF in plasma and on surface of blood dendritic cells (DC) of HIV-infected progressors coincides with B-cell dysregulations and increased frequencies of "precursor" innate marginal zone (MZ)-like B-cells. In contrast, both blood BLyS levels and frequencies of this population remained unaltered in HIV elite-controllers. Based on these observations, we hypothesized that control of BLyS and innate B-cell status could be associated with natural immunity against HIV infection...
2016: Scientific Reports
Meghan K Eberhardt, Ashlesha Deshpande, Joseph Fike, Rebecca Short, Kimberli A Schmidt, Shelley A Blozis, Mark R Walter, Peter A Barry
: There is accumulating evidence that the viral interleukin-10 (vIL-10) ortholog of both human and rhesus cytomegalovirus (HCMV and RhCMV, respectively) suppresses the functionality of cell types that are critical to contain virus dissemination and help shape long-term immunity during the earliest virus-host interactions. In particular, exposure of macrophages, peripheral blood mononuclear cells, monocyte-derived dendritic cells, and plasmacytoid dendritic cells to vIL-10 suppresses multiple effector functions including, notably, those that link innate and adaptive immune responses...
November 1, 2016: Journal of Virology
Jennifer M Lund, Kristina Broliden, Maria N Pyra, Katherine K Thomas, Deborah Donnell, Elizabeth Irungu, Timothy R Muwonge, Nelly Mugo, Madhuri Manohar, Marianne Jansson, Romel Mackelprang, Mark A Marzinke, Jared M Baeten, Jairam R Lingappa
: Although nonhuman primate studies have shown that simian immunodeficiency virus/simian-human immunodeficiency virus (SIV/SHIV) exposure during preexposure prophylaxis (PrEP) with oral tenofovir can induce SIV immunity without productive infection, this has not been documented in humans. We evaluated cervicovaginal IgA in Partners PrEP Study participants using a subtype C primary isolate and found that women on PrEP had IgA with higher average human immunodeficiency virus type 1 (HIV-1)-neutralizing magnitude than women on placebo (33% versus 7%; P = 0...
November 1, 2016: Journal of Virology
Victor Barreto-de-Souza, Anush Arakelyan, Sonia Zicari, Leonid Margolis, Christophe Vanpouille
: Unprotected sexual intercourse with HIV-infected men is the major cause of new infections. HIV virions are released into semen by various cells of the male genital tract, as well as by infected monocytes and lymphocytes present in semen. Some of these virions may attach to the surfaces of cells, infected or uninfected. We investigated whether cells carrying attached HIV on their surfaces can transmit infection. We addressed this question in a model system of human tissue exposed ex vivo to monocytes and lymphocytes carrying HIV on their surfaces...
November 1, 2016: Journal of Virology
Catherine G Sutcliffe, Donald M Thea, Philip Seidenberg, James Chipeta, Lawrence Mwyanayanda, Somwe Wa Somwe, Julie Duncan, Magdalene Mwale, Justin Mulindwa, Musaku Mwenechenya, Rasa Izadnegahdar, William J Moss
BACKGROUND: Pneumonia is the leading infectious cause of death among children, with approximately half of deaths attributable to pneumonia occurring in limited health resource settings of sub-Saharan Africa. Clinical guidance tools and checklists have been used to improve health outcomes and standardize care. This study was conducted to evaluate the impact of a clinical guidance tool designed to improve outcomes for children hospitalized with severe pneumonia in Zambia. METHODS: This study was conducted at University Teaching Hospital in Lusaka, Zambia from October 10, 2011 to March 21, 2014 among children 1 month to 5 years of age with severe pneumonia...
2016: BMC Pediatrics
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