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HIV-1 seroreversion in HIV-1-infected children: do genetic determinants play a role?

Asang, Corinnaa; Laws, Hans-J.a; Adams, Ortwinb; Enczmann, Jürgenc; Feiterna-Sperling, Corneliad; Notheis, Gundulae; Buchholz, Berndf; Borkhardt, Arndta; Neubert, Jennifera

doi: 10.1097/QAD.0000000000000065
Clinical Science: Concise Communication

Background: HIV-1 seroreversion in infants with vertically transmitted HIV-1 infection who started ART in the first months of life has been reported in only a subset of patients. However, the reason why most infants remain seropositive despite similar treatment response is not understood. Here, we assessed whether HIV-1 seroreversion in maternally infected infants is associated with genetic determinants.

Methods: HIV-1-infected infants with a history of documented HIV-1 seroreversion were identified throughout Germany using a standardized questionnaire. At study entry immune reconstitution and anti-HIV-1 antibody expression were monitored as clinical parameters. To search for genetic determinants high-resolution HLA genotyping was performed. In addition, the coding sequence of the chemokine receptor CCR5 was analyzed by Sanger sequencing regarding potential mutations.

Results: Patients showed normal numbers and frequencies of lymphocyte subpopulations. Five out of eight patients still had seronegative HIV-1 antibody status at study entry. HLA genotyping revealed the enrichment of HLA-DQB1*03 and DQB1*06 alleles within the patient cohort. Only one patient was found to carry a 32 bp-deletion within the CCR5 gene.

Conclusion: Our results indicate that the phenotype of HIV-1 seroreversion in infants might correlate with the presence of HLA class II alleles DQB1*03 and DQB1*06. This finding supports the idea of genetic predisposition determining HIV-1 seroreversion in vertically infected infants effectively treated with ART.

aDepartment of Pediatric Oncology, Hematology and Clinical Immunology, Center for Child and Adolescent Health

bInstitute for Virology, Medical Faculty

cBone Marrow Donor Center with Eurocord Bank and Transplantation Immunology, Heinrich-Heine-University Düsseldorf, Düsseldorf

dDepartment of Pediatric Pneumology and Immunology, Charité University Medicine Berlin, Berlin

eChildren Hospital, Ludwig Maximilians University, Munich

fUniversity Medical Center Mannheim, Pediatric Clinic, Mannheim, Germany.

Correspondence to Jennifer Neubert, Heinrich-Heine-University Düsseldorf, Medical Faculty, Department of Pediatric Oncology, Hematology and Clinical Immunology, Moorenstrasse 5, 40225 Düsseldorf, Germany. Tel: +492118118297; e-mail: Jennifer.neubert@uni-duesseldorf.de

Received 28 May, 2013

Revised 3 September, 2013

Accepted 3 September, 2013

Copyright © 2014 Wolters Kluwer Health, Inc.