Towards Detection of Unknown GMOs

The state-of-the-art technology for detection of genetically modified organisms (GMOs) is polymerase chain reaction. The targets are novel sequences such as genes, but the insertion locus sequences are also important for GMO identification. GMOs go through a series of developmental stages, in which field trials precede commercial releases. GMO developers only exceptionally publish details on inserted novel sequences unless such publication is, for example, required by legislation. Information on novel sequences of GMOs may therefore be sparse, and in some cases completely missing, making the development and implementation of detection methods extremely difficult. In this chapter, we present an overview of the problems and proposed possible solutions to challenges associated with detection and correct identification of GMOs, with particular emphasis on unknown GMO

Neurologic signs in young children with human immunodeficiency virus infection

Neurologic and neurodevelopmental problems were investigated in a cohort of 39 human immunodeficiency virus (HIV)-infected children and 164 antibody-negative children born to HIV-positive women. All children were followed from birth for between 1 month and 4 years. Serious neurologic manifestations were present in 5 of 16 children (31%) who developed acquired immunodeficiency syndrome/acquired immunodeficiency syndrome-related complex, although in 2 the neurologic signs were probably not related to HIV. This can be compared with a prevalence of 0 of 23 in children who remained asymptomatic or who had less severe HIV-related symptoms or signs and 2 of 164 (1%) in uninfected children. Neurologic signs in the uninfected group were associated with the presence of drug withdrawal at birth and prematurity. These findings contrast with reports of a high prevalence of neurologic findings in most studies of HIV-infected children

CD4 cell response to antiretroviral therapy in children with vertically acquired HIV infection: Is it associated with age at initiation?

Background. Considerable uncertainty remains as to whether early initiation of antiretroviral therapy (ART) in children with vertically acquired human immunodeficiency virus (HIV) infection increases the benefit in terms of immunological response. Methods. The association between immunological outcome and early initiation of and/or more-potent ART was investigated, using age-standardized z scores for CD4 cell counts (hereafter, "CD4 z scores"), in 131 HIV-infected children enrolled in the European Collaborative Study, a birth cohort study. Results. Median age at initiation of the most-potent ART was 4 years (range, 0.1-15.5 years). Initiation of treatment after 5 months of age resulted in nonsignificantly lower CD4 z scores 6 months after initiation. Time to a 20% increase in CD4 z score was associated with age at initiation of the most-potent ART (adjusted hazard ratios [AHRs], 0.37 [P<.01] and 0.43 [P = .05] for 5 months-5 years of age and >5 years of age, respectively, compared with <5 months of age), ethnicity (AHR, 0.48 [P = .01], for black vs. white), and highly active ART (HAART) with or without prior ART (AHRs, 3.16 [P<.01] and 3.95 [P<.001], vs. mono or dual ART, respectively). The risk of subsequent deterioration of CD4 z score was similar for children who initiated ART in different age groups (\u3c72 = 0.824; P = .82). Conclusions. We confirm the effectiveness of HAART with respect to the recovery of CD4 cell count and suggest a benefit of initiating ART before the age of 5 months. Age at initiation of the most-potent ART was not associated with the likelihood of sustaining the recovery of CD4 cell count

Levels and patterns of neutrophil cell counts over the first 8 years of life in children of HIV-1-infected mothers

Background: Antiretroviral drugs (ARV) as prophylaxis to prevent mother-to-child transmission of HIV results in decreased haematological parameters during and shortly after exposure, with recent data suggesting a more prolonged inhibition of haematopoiesis until at least 18 months. Design: Data on 156 HIV-infected and 1533 uninfected children in the European Collaborative Study followed from birth until at least 8 years of age. Methods: Smoothers and splines were used to elucidate patterns over age; linear mixed effects allowed for repeated measurements. Covariates included the child's HIV-1 infection status, prematurity, gender, race, drug withdrawal symptoms at birth and ARV exposure; effects on neutrophil count were quantified in regression analyses using z-scores (SD from mean) of neutrophil counts obtained after modelling untransformed values using the LMS method. For HIV-infected children, progression to AIDS and ARV therapy were also included. Results: After approximately 4 months of age, neutrophil counts were consistently and substantially lower in HIV-infected children than in uninfected children; in both groups, black children had significantly lower counts than white children across the whole age range. In uninfected children, male gender and ARV exposure were associated with reduced neutrophil count until at least 8 years of age. In HIV-infected children, advanced disease and ARV treatment were significantly associated with neutrophil count. Conclusion: A considerably longer effect of exposure to ARV was shown in uninfected children than previously thought and significant associations were shown between race and gender and neutrophil count, as previously observed for lymphocyte counts. The clinical relevance of these reduced levels of neutrophils requires further investigation

Therapeutic and other interventions to reduce the risk of mother-to-child transmission of HIV-1 in Europe. The European Collaborative Study

C. Thorne, M.-L. Newell, A. Bailey, C.S. Peckham, C. Giaquinto, E. Ruga, A. De Rossi, D. Truscia, I. Grosch-Worner, A. Schafer, J. Mok, F. Johnstone, F. Omenaca, J. Jiminez, C.De Alba, M.C. Garcia-Rodriguez, I. Bates, I. De Jose, F. Hawkins, R. Martinez Zapico, F. Asensi-Botet, M.C. Otero, D. Perez-Tamarit, A. Gonzalez Molina, H. Canosa, H. Scherpbier, K. Boer, A.B. Bohlin, S. Lindgren, E. Belfrage, J. Levy, A. Alimenti, P. Barlow, A. Ferrazin, A. Dre Maria, C. Gotta, V. Maritati, A. Mur, M.T. Rovira, A. Paya, O. Coll, C. Fortuny, J. Boguna, M. Casellas Caro, Y. Canet, G. Pardi, A.E. Semprini, M. Ravizza, C. Castagna, S. Fiore, B. Guerra, S. Bianchi, L. Bovicelli, E. Prati, S. Zanelli, M. Duse, A. Soresina, G. Scaravelli, M. Stegagno, M. De Santis, M.-L. Muggiasca, P. Marchisio, A. Iasci, A. Spinillo, A. Bucceri, E. Grossi, L. Rancilio, R. Smith, A.-M. Lewi

Exposure to antiretroviral therapy in utero or early life : the health of uninfected children born to HIV infected women

Concerns have been raised over possible adverse effects of prophylactic antiretroviral therapy (ART) on the fetus and newborn. We analyzed data relating to uninfected children enrolled in the European Collaborative Study and investigated the association between ART exposure, perinatal problems, and major adverse health events later in life. Median length of follow-up was 2.2 (0-15.9) years. Of the 2414 uninfected children, 687 (28%) were exposed to ART in all three periods (antenatal, intrapartum, and neonatal). Of the 1008 infants exposed to ART at any time, 906 (90%) were exposed antenatally, 840 (83%) neonatally, and 750 (74%) both antenatally and neonatally. ART exposure was not significantly associated with pattern or prevalence of congenital abnormalities or low birth weight. In multivariate analysis, prematurity was associated with exposure to combination therapy without a protease inhibitor (PI) (OR = 2.66; 95% CI: 1.52-4.67) and with a PI (OR = 4.14; 95% CI: 2.36-7.23). ART exposure was associated with anemia in early life (p < .001). There was no evidence of an association with clinical manifestations suggestive of mitochondrial abnormalities. The absence of serious adverse events in this large cohort of uninfected children exposed to prophylactic ART in the short to medium term is reassuring

Effects of mode of delivery and infant feeding on the risk of mother-to-child transmission of hepatitis C virus

Objective To investigate the effects of mode of delivery and infant feeding on the risk of mother-to-child transmission of hepatitis C virus. Design Pooled retrospective analysis of prospectively collected data. Sample Data on hepatitis C virus seropositive mothers and their children identified around delivery were sent from 24 centres of the European Paediatric Hepatitis C Virus Network. Main outcome measures Hepatitis C virus infection status of children born to hepatitis C virus infected women. Results A total of 1,474 hepatitis C virus infected women were identified, of whom 503 (35%) were co-infected with HIV. Co-infected women were more than twice as likely to transmit hepatitis C virus to their children than women with hepatitis C virus infection alone. Overall 9.2% (136/1474) of children were hepatitis C virus infected. Among the women with hepatitis C virus infection-only, multivariate analyses did not show a significant effect of mode of delivery and breastfeeding: caesarean section vs vaginal delivery OR=1.17, P=0.66; breastfed versus non-breastfed OR=1.07, P=0.83. However, HIV co-infected women delivered by caesarean section were 60% less likely to have an infected child than those delivered vaginally (OR=0.36, P=0.01) and those who breastfed were about four times more likely to infect their children than those who did not (OR=6.41, P=0.03). HIV infected children were three to four times more likely also to be hepatitis C virus infected than children without HIV infection (crude OR=3.76, 95% CI 1.89\u20137.41). Conclusions These results do not support a recommendation of elective caesarean section or avoidance of breastfeeding for women with hepatitis C virus infection only, but the case for HIV infected women undergoing caesarean section delivery and avoiding breastfeeding is strengthened if they are also hepatitis C virus infected

Impact of human immunodeficiency virus type 1 subtypes on virologic response and emergence of drug resistance among children in the Paediatric European Network for Treatment of AIDS (PENTA) 5 trial

The association between virologic response and human immunodeficiency virus type 1 (HIV-1) subtype was investigated in 113 HIV-1-infected children randomly assigned to receive zidovudine plus lamivudine, zidovudine plus abacavir, or lamivudine plus abacavir in the Paediatric European Network for Treatment of AIDS (PENTA) 5 trial. Symptomatic children (n = 68) also received nelfinavir; asymptomatic children (n = 45) were randomly assigned to receive nelfinavir or placebo. HIV-1 subtypes A, B, C, D, F, G, H, A/E, and A/G were found in 15%, 41%, 16%, 9%, 5%, 2%, 1%, 5%, and 7% of the children, respectively. Resistance assay failure rates were higher for non-B subtypes than for B subtypes (genotype, P = .01; phenotype, P = .02). HIV-1 subtype was not associated with virologic response at 24 and 48 weeks after initiation of treatment. No differences were observed in the frequency of development of resistance mutations L90M (P = 1.00) and D30N (P = .61) in B and non-B viruses. In conclusion, no evidence that subtype determined virologic response to therapy was found