Next generation DNA sequencing is used to determine the HLA-A, -B, -C, -DRB1, and -DQB1 assignments of 1472 unrelated volunteers for the unrelated donor registry in Argentina. The analysis characterized all HLA exons and introns for class I alleles; at least exons 2, 3 for HLA-DRB1; and exons 2 to 6 for HLA-DQB1. Of the distinct alleles present, there are 330 class I and 98 class II. The majority (~98%) of the cumulative allele frequency at each locus is contributed by alleles that appear at a frequency of at least 1 in 1000. Fourteen (18.2%) of the 77 novel class I and II alleles carry nonsynonymous variation within their exons; 52 (75.4%) class I novel alleles carry only single, apparently random, nucleotide variation within their introns/untranslated regions. Alleles encoding protein variation not usually detected by typing focused only on the exons encoding the antigen recognition domain are 1.0% of the class I assignments and 7.3% of the class II assignments (predominantly DQB1*02:02:01, DQB1*03:19:01, and DRB1*14:54:01). Updates to the common and well documented list of alleles include 10 alleles previously thought to be uncommon but that are found at least 30 times. Five locus haplotypes estimated using the expectation-maximization algorithm as present 3 or more times total 187. While the known HLA diversity continues to increase, the conservation of known allele sequences is remarkable. Overall, the HLA diversity observed in the Argentinian population reflects its European and Native American ancestry.
Next generation DNA sequencing is used to determine the HLA‐A, ‐B, ‐C, ‐DRB1, ‐DRB3/4/5, and ‐DQB1 assignments of 1009 unrelated volunteers for the unrelated donor registry in The Netherlands. The analysis characterizes all HLA exons and introns for class I alleles; at least exons 2 to 3 for HLA‐DRB1; and exons 2 to 6 for HLA‐DQB1. Of the distinct alleles present, there are 229 class I and 71 class II; 36 of these alleles are novel. The majority (approximately 98%) of the cumulative allele frequency at each locus is contributed by alleles that appear three or more times. Alleles encoding protein variation outside of the antigen recognition domains are 0.6% of the class I assignments and 5.3% of the class II assignments.
ABSTRACT. Objective. To describe the extent of adherence to the recommended neonatal zidovudine (ZDV) regimen administered to infants who have been exposed to the human immunodeficiency virus (HIV) to prevent mother-to-child transmission of HIV and to determine which maternal factors are associated with compliance.Methods. HIV-infected women (n ؍ 87) who were participating in a larger study of perinatal transmission at 3 inner-city New York City hospitals were interviewed 2 to 6 weeks' postpartum to assess adherence to neonatal prophylaxis, social support, social network factors, and depression. In addition, plasma samples of 45 of their infants were assayed for ZDV levels.Results. A majority of women (71%) administered all of the prescribed 4 daily doses in the previous week, as measured by interview; self-reported adherence was not associated with any maternal characteristics. In contrast, poor adherence, as measured by lower infant ZDV plasma levels, was associated with asymptomatic HIV illness in the mother and having 2 or more other children; good adherence, as indicated by higher ZDV levels, was associated with the presence of a maternal social support network, disclosure of HIV infection, and mothers' adherence to their own ZDV regimens during pregnancy. In multivariate regression analyses, maternal asymptomatic status ( ؍ ؊0.40) was associated with lower infant ZDV levels, and maternal adherence during pregnancy ( ؍ 0.37) was associated with higher levels.Conclusions. Women who are HIV asymptomatic and lack a social support network are more likely not to comply with the recommended neonatal prophylactic regimen of antiretroviral therapy. Future studies should address the prenatal period and social network factors, such as disclosure of serostatus, and the custody of other children. Pediatrics 2002;110(3). URL: http://www. pediatrics.org/cgi/content/full/110/3/e35; adherence, mother-to-child transmission, zidovudine, perinatal HIV infection. Prophylactic treatment of all infected pregnant women and their infants with the 076 regimen was subsequently recommended by the US Public Health Service 2 and rapidly became the standard of care. A later study indicated reduced transmission rates in infants who were treated with ZDV within 48 hours of birth, even in the absence of maternal treatment. 3 The current prophylaxis for full-term HIV-exposed infants includes a 6-week course of oral ZDV 4 times daily in doses of 2 mg/kg body weight, initiated as soon as possible, and within 12 to 24 hours of delivery. 2 Understanding factors that are associated with adherence to neonatal prophylaxis has become increasingly important as greater proportions of HIV-exposed infants are being identified and treated as a result of more aggressive prenatal HIV testing policies 4 and recent advances in rapid HIV testing technology that could expedite the initiation of treatment for exposed neonates. 5 In August 1999, New York became the first state to legislate universal testing of women with undocumented HIV status or their...
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