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Effects of antiretroviral agents during pregnancy on liver enzymes and amylase in HIV-exposed, uninfected newborn infants
El Beitune, Patrícia;Duarte, Geraldo;Campbell, Oona;Quintana, Silvana Maria;Rodrigues, Laura C.;
Brazilian Journal of Infectious Diseases , 2007, DOI: 10.1590/S1413-86702007000300003
Abstract: this study assessed the effect of antiretroviral drugs administered to pregnant women on amylase and liver enzymes of the neonate. a prospective study was conducted on 52 neonates divided into three groups: infants born to hiv-infected mothers taking zidovudine (zdv group, n = 18), infants born to mothers taking zidovudine + lamivudine + nelfinavir (tt group, n = 22) and infants born to normal women (control group, n = 12). umbilical cord blood from the newborn infant was used to determine liver transaminases and amylase. data were analyzed statistically by nonparametric tests, with the level of significance set at p<0.05. the median levels for tt group newborns were 33.3 u/l for oxaloacetic transaminase, 21.5 u/l for pyruvic transaminase, 1.9 mg/dl for total bilirubin, 153 mg/dl for alkaline phosphatase, and 9.6 u/l for amylase. these results did not differ from those obtained for control newborns or newborns exposed to zdv alone. no association was observed between the use of antiretroviral drugs during pregnancy and adverse effects on neonatal amylase and hepatic parameters at birth.
Growth and Development of the HIV Exposed Uninfected Children below 5 Years in Developing Countries: Focus on Nutritional Challenges, Mortality and Neurocognitive Function  [PDF]
Patience Kuona, Gwendoline Kandawasvika, Felicity Gumbo, Kusum Nathoo, Babill Stray-Pedersen
Food and Nutrition Sciences (FNS) , 2014, DOI: 10.4236/fns.2014.520211
Abstract: The future of any population is children. Resource limited settings with a high prevalence of HIV infection notably also have an excessive burden of malnutrition. The advances in prevention of mother to child HIV transmission programmes have led to very effective combination antiretroviral regimens resulting in growing numbers of HIV exposed but uninfected children. The mortality of HIV exposed but uninfected children below 5 years is high in resource limited settings. It is also important to pay particular attention to their longitudinal growth and neurodevelopmental outcomes. In these settings, the contribution of feeding practices, choice of complementary foods and micronutrient deficiencies, to health outcomes of HIV exposed uninfected children are not clearly defined. This review highlights some gaps in research that need to be addressed in areas with increasing numbers of HIV exposed but uninfected children. Interventions to reduce mortality, improve growth and neurodevelopmental outcomes in HIV exposed uninfected children from resource limited areas should be prioritized.
HIV and pregnancy: Maternal and neonatal evolution
Cecchini,Diego; Urue?a,Analía; Trinidad,Patricia; Vesperoni,Fernando; Mecikovsky,Débora; Bologna,Rosa;
Medicina (Buenos Aires) , 2011,
Abstract: data regarding epidemiological aspects, antiretroviral drug safety, and outcomes of hiv-infected pregnant women and their newborns are limited in argentina. we underwent a retrospective analysis of registries of hiv-infected pregnant women assisted at helios salud, buenos aires, argentina (1997-2006). variables associated with preterm delivery and neonatal complications were analyzed by univariate and logistic regression analyses. a total of 204 mother-child binomium were included. maternal age (median): 29 years; 32.5% without prior diagnosis of hiv-infection. baseline median cd4 t-cell count: 417 cell/μl; 98% received antiretroviral drugs during pregnancy [2 nucleoside analogs plus either nevirapine (55%) or a protease inhibitor (32%)]. overall incidence of toxicity was 12.5%: rash (8%), anemia (3.5%) and hepatotoxicity (1%). rash was associated with exposure to nevirapine. eighty one percent and 50% reached hiv-viral loads <1000 and <50 copies/ml at the end of pregnancy, respectively. twenty six percent had obstetric complications and 16% had preterm delivery. of the newborns, 1.6% had congenital defects and 9% had neonatal complications. overall neonatal mortality was 1% and perinatal transmission was 0.7%. protease inhibitor use and obstetric complications were associated to preterm delivery while obstetric complications were associated with neonatal complications. in our population, hepatotoxicity was low despite frequent use of nevirapine. protease inhibitor use was associated to preterm delivery. a favorable virological response and a low rate of perinatal transmission was observed, what supports the consensus that antiretroviral therapy benefits during pregnancy outweigh risks of maternal and neonatal adverse events.
Neurodevelopmental status of HIV-exposed but uninfected children: A pilot study
P Springer, B Laughton, M Tomlinson, J Harvey, M Esser
South African Journal of Child Health , 2012,
Abstract: Introduction. HIV affects children both directly and indirectly, with evidence of increased infectious mortality and morbidity in the HIV-exposed but uninfected (HEU) infant. There is little published research on neurodevelopmental outcome of HEU infants in Africa. Following the introduction of successful prevention of mother-to-child transmission programmes, it has become important to determine whether differences exist between HEU infants and infants born to HIV-negative mothers in order to guide current management policies of this rapidly growing group of infants. Objectives. To compare the developmental outcome of infants exposed to HIV in utero who remained uninfected (HEU) with that of infants unexposed to HIV in utero (HUU). Methodology. This was a prospective, blinded, hospital-based study. Infants aged between 17 and 19 months were assessed on the Griffiths Mental Developmental Scales (GMDS). Birth history, previous hospitalisation, maternal and infant characteristics, antiretroviral exposure, anthropometric measurements and abnormal clinical findings were documented. Results. Of the original 55 infants enrolled at 2 weeks of age, 37 (17 HEU and 20 HUU) underwent neurological and developmental assessment. There were no significant differences between the groups with regard to the GMDS general quotient or other subscales, apart from the Personal/social subscale, where the HEU group performed significantly more poorly than the HUU participants (p=0.026). This difference is probably a result of cultural differences between the groups, as 76% of HEU and only 15% of HUU participants were of Xhosa origin. Discussion. There was no difference in neurodevelopmental outcome at 18 months between the HEU and HUU groups.
Low Birth Weight in Perinatally HIV-Exposed Uninfected Infants: Observations in Urban Settings in Cameroon  [PDF]
Casimir Ledoux Sofeu, Josiane Warszawski, Francis Ateba Ndongo, Ida Calixte Penda, Suzie Tetang Ndiang, Georgette Guemkam, Nicaise Makwet, Félicité Owona, Anfumbom Kfutwah, Patrice Tchendjou, Ga?tan Texier, Maurice Tchuente, Albert Faye, Mathurin Cyrille Tejiokem, The ANRS-PEDIACAM study group
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0093554
Abstract: Background The consequences of maternal HIV infection for fetal growth are controversial. Here, we estimated the frequency of small for gestational age and gender (SGAG) among neonates born to HIV-infected or uninfected mothers and assessed the contribution, if any, of maternal HIV to the risk of SGAG. Methods The data used were obtained from the ANRS-Pediacam cohort in Cameroon. Pairs of newborns, one to a HIV-infected mother and the other to an uninfected mother, were identified during the first week of life, and matched on gender and recruitment site from 2007–2010. SGAG was defined in line with international recommendations as a birth weight Z-score adjusted for gestational age at delivery and gender more than two standard deviations below the mean (?2SD). Considering the matched design, logistic regression modeling was adjusted on site and gender to explore the effect of perinatal HIV exposure on SGAG. Results Among the 4104 mother-infant pairs originally enrolled, no data on birth weight and/or gestational age were available for 108; also, 259 were twins and were excluded. Of the remaining 3737 mother-infant pairs, the frequency of SGAG was 5.3% (95%CI: 4.6–6.0), and was significantly higher among HIV-infected infants (22.4% vs. 6.3%; p<.001) and lower among HIV-unexposed uninfected infants (3.5% vs. 6.3%; p<.001) than among HIV-exposed uninfected infants. Similarly, SGAG was significantly more frequent among HIV-infected infants (aOR: 4.1; 2.0–8.1) and less frequent among HIV-unexposed uninfected infants (aOR: 0.5; 0.4–0.8) than among HIV-exposed uninfected infants. Primiparity (aOR: 1.9; 1.3–2.7) and the presence of any disease during pregnancy (aOR: 1.4; 1.0–2.0) were identified as other contributors to SGAG. Conclusion Maternal HIV infection was independently associated with SGAG for HIV-exposed uninfected infants. This provides further evidence of the need for adapted monitoring of pregnancy in HIV-infected women, especially if they are symptomatic, to minimize additional risk factors for SGAG.
Leukocyte Telomere Length in HIV-Infected and HIV-Exposed Uninfected Children: Shorter Telomeres with Uncontrolled HIV Viremia  [PDF]
Hélène C. F. C?té, Hugo Soudeyns, Anona Thorne, Ariane Alimenti, Valérie Lamarre, Evelyn J. Maan, Beheroze Sattha, Joel Singer, Normand Lapointe, Deborah M. Money, John Forbes, the CIHR Emerging Team in HIV therapy, aging (CARMA)
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0039266
Abstract: Objectives Nucleoside reverse transcriptase inhibitors (NRTIs) used in HIV antiretroviral therapy can inhibit human telomerase reverse transcriptase. We therefore investigated whether in utero or childhood exposure to NRTIs affects leukocyte telomere length (LTL), a marker of cellular aging. Methods In this cross-sectional CARMA cohort study, we investigated factors associated with LTL in HIV -1-infected (HIV+) children (n = 94), HIV-1-exposed uninfected (HEU) children who were exposed to antiretroviral therapy (ART) perinatally (n = 177), and HIV-unexposed uninfected (HIV?) control children (n = 104) aged 0–19 years. Univariate followed by multivariate linear regression models were used to examine relationships of explanatory variables with LTL for: a) all subjects, b) HIV+/HEU children only, and c) HIV+ children only. Results After adjusting for age and gender, there was no difference in LTL between the 3 groups, when considering children of all ages together. In multivariate models, older age and male gender were associated with shorter LTL. For the HIV+ group alone, having a detectable HIV viral load was also strongly associated with shorter LTL (p = 0.007). Conclusions In this large study, group rates of LTL attrition were similar for HIV+, HEU and HIV? children. No associations between children’s LTL and their perinatal ART exposure or HIV status were seen in linear regression models. However, the association between having a detectable HIV viral load and shorter LTL suggests that uncontrolled HIV viremia rather than duration of ART exposure may be associated with acceleration of blood telomere attrition.
Pathogenic lower genital tract organisms in HIV-infected and uninfected women, and their association with postpartum infectious morbidity
HM Sebitloane, J Moodley, TM Esterhuizen
South African Medical Journal , 2011,
Abstract: Objectives. To determine the prevalence of vaginal pathogens during pregnancy and their impact on postpartum infectious morbidity among antiretroviral-na ve HIV-infected, and HIVuninfected, women. Methods. Vaginal swabs were obtained during early labour by speculum examination prior to digital vaginal examination, and sent for microscopy and culture. Women were assessed for infectious complications within 24 - 72 hours of delivery, and up to 2 weeks postpartum. Results. Laboratory results were available for 801 women who delivered vaginally (418 HIV infected and 383 uninfected). The baseline characteristics of the two groups were comparable, and the median CD4 count for HIV-infected women (N=391) was 416/μl. Fifty-five per cent (54.8%) of women had positive cultures (439/801), more among those who were HIV infected than uninfected (60% v. 49.1%, p=0.002). Women with positive cultures had slightly higher rates of infectious morbidity than those without (20.5% v. 15.2%, p=0.052). Trichomonas vaginalis and group B streptococci were significantly associated with sepsis (p=0.023 and <0.001, respectively), whereas the presence of Candida species seemed to be protective (relative risk 0.69, p=0.014). Conclusion. The study shows that a high proportion of pregnant women have pathogenic organisms in the lower genital tract that are associated with development of postpartum infectious morbidity.
The impact of maternal HIV infection on cord blood lymphocyte subsets and cytokine profile in exposed non-infected newborns
Eliane Borges-Almeida, Helaine MBPM Milanez, Maria Marluce S Vilela, Fernanda GP Cunha, Beatriz M Abramczuk, Suiellen C Reis-Alves, Konradin Metze, Irene Lorand-Metze
BMC Infectious Diseases , 2011, DOI: 10.1186/1471-2334-11-38
Abstract: In a prospective, controlled study, 36 mother-child pairs from HIV+ mothers and 15 HIV-uninfected mothers were studied. Hematological features and cytokine profiles of mothers at 35 weeks of pregnancy were examined. Maternal and cord lymphocyte subsets as well as B-cell maturation in cord blood were analyzed by flow cytometry. The non-stimulated, as well as BCG- and PHA-stimulated production of IL2, IL4, IL7, IL10, IL12, IFN-γ and TNF-alpha in mononuclear cell cultures from mothers and infants were quantified using ELISA.After one year follow-up none of the exposed infants became seropositive for HIV. An increase in B lymphocytes, especially the CD19/CD5+ ones, was observed in cord blood of HIV-exposed newborns. Children of HIV+ hard drug using mothers had also an increase of immature B-cells. Cord blood mononuclear cells of HIV-exposed newborns produced less IL-4 and IL-7 and more IL-10 and IFN-γ in culture than those of uninfected mothers. Cytokine values in supernatants were similar in infants and their mothers except for IFN-γ and TNF-alpha that were higher in HIV+ mothers, especially in drug abusing ones. Cord blood CD19/CD5+ lymphocytes showed a positive correlation with cord IL-7 and IL-10. A higher maternal age and smoking was associated with a decrease of cord blood CD4+ cells.in uninfected infants born to HIV+ women, several immunological abnormalities were found, related to the residual maternal immune changes induced by the HIV infection and those associated with antiretroviral treatment. Maternal smoking was associated to changes in cord CD3/CD4 lymphocytes and maternal hard drug abuse was associated with more pronounced changes in the cord B cell line.HIV infection is associated with a complex pattern of changes in the hemopoietic and the immune systems, resulting in abnormalities of peripheral blood (PB) counts and changes in T and B lymphocytes. Decrease of T helper and increase of cytotoxic lymphocytes, profound changes in the cytokine profile and a
Effect of antiretroviral drugs on maternal CD4 lymphocyte counts, HIV-1 RNA levels, and anthropometric parameters of their neonates
El Beitune, Patrícia;Duarte, Geraldo;Machado, Alcyone Artioli;Quintana, Silvana Maria;Figueiró-Filho, Ernesto A.;Abduch, Renata;
Clinics , 2005, DOI: 10.1590/S1807-59322005000300005
Abstract: purpose: to study the effect of antiretroviral drugs administered during pregnancy on cd4 lymphocyte counts and hiv-1 rna levels of pregnant women and on the anthropometric parameters of their neonates. methods: a prospective study was conducted on 57 pregnant women and their neonates divided into 3 groups: zdv group, hiv-infected mothers taking zidovudine (n = 20); triple therapy (tt) group, mothers taking zidovudine + lamivudine + nelfinavir (n = 25), and control group, normal women (n = 12). cd4 lymphocyte counts and hiv-1 rna levels of pregnant women were analyzed during two periods of pregnancy. the perinatal prognosis took into account preterm rates, birth weight, intrauterine growth restriction, perinatal death, and vertical transmission of hiv-1. data were analyzed statistically using the nonparametric chi-square, mann-whitney, friedman, kruskal-wallis, and wilcoxon matched pairs tests, with the level of significance set at p <.05. results: the major maternal demographic and anthropometric data were homogeneous for the various groups. hiv-1 viral burden, which was initially elevated, median of 14,370 copies/ml, was significantly reduced in the tt group, reaching 40 copies/ml. with respect to t-cd4+ lymphocyte counts, there was a significant recovery in group tt at the end of pregnancy, this value being significantly different from that for the zdv group (p =.0052). there was no difference between groups regarding gestation length, apgar scores, or neonatal anthropometric classification. there was no case of vertical hiv-1 transmission. conclusions: the results obtained for the present series demonstrate the efficiency and suggest safety of the use of antiretroviral drugs during pregnancy as revealed by anthropometric parameters of the neonate.
HIV and pregnancy: Maternal and neonatal evolution HIV y embarazo: Evolución materna y neonatal  [cached]
Diego Cecchini,Analía Urue?a,Patricia Trinidad,Fernando Vesperoni
Medicina (Buenos Aires) , 2011,
Abstract: Data regarding epidemiological aspects, antiretroviral drug safety, and outcomes of HIV-infected pregnant women and their newborns are limited in Argentina. We underwent a retrospective analysis of registries of HIV-infected pregnant women assisted at Helios Salud, Buenos Aires, Argentina (1997-2006). Variables associated with preterm delivery and neonatal complications were analyzed by univariate and logistic regression analyses. A total of 204 mother-child binomium were included. Maternal age (median): 29 years; 32.5% without prior diagnosis of HIV-infection. Baseline median CD4 T-cell count: 417 cell/μl; 98% received antiretroviral drugs during pregnancy [2 nucleoside analogs plus either nevirapine (55%) or a protease inhibitor (32%)]. Overall incidence of toxicity was 12.5%: rash (8%), anemia (3.5%) and hepatotoxicity (1%). Rash was associated with exposure to nevirapine. Eighty one percent and 50% reached HIV-viral loads <1000 and <50 copies/ml at the end of pregnancy, respectively. Twenty six percent had obstetric complications and 16% had preterm delivery. Of the newborns, 1.6% had congenital defects and 9% had neonatal complications. Overall neonatal mortality was 1% and perinatal transmission was 0.7%. Protease inhibitor use and obstetric complications were associated to preterm delivery while obstetric complications were associated with neonatal complications. In our population, hepatotoxicity was low despite frequent use of nevirapine. Protease inhibitor use was associated to preterm delivery. A favorable virological response and a low rate of perinatal transmission was observed, what supports the consensus that antiretroviral therapy benefits during pregnancy outweigh risks of maternal and neonatal adverse events. La información sobre aspectos epidemiológicos, seguridad de drogas antirretrovirales y evolución de mujeres embarazadas HIV positivas y sus hijos es limitada en la Argentina. Realizamos un análisis retrospectivo de registros de embarazadas HIV positivas asistidas en Helios Salud, Buenos Aires, Argentina (1997-2006). Las variables asociadas con parto prematuro y complicaciones neonatales se estudiaron mediante análisis univariado y regresión logística. Estudiamos 204 binomios madre-hijo. Edad materna (mediana): 29 a os, 32.5% sin diagnóstico previo de HIV. Recuento de linfocitos T CD4+ (mediana): 417 células/μl. El 98% recibió tratamiento antirretroviral durante el embarazo [dos análogos de nucleósidos más nevirapina (55%) o un inhibidor de proteasa (32%)]. La incidencia global de toxicidad fue 12.5%: erupción cutánea (8%), anemia (3
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