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


CONCLUSIONS
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.
Corinna
C
Asang
Hans-J
HJ
Laws
Ortwin
O
Adams
Jürgen
J
Enczmann
Cornelia
C
Feiterna-Sperling
Gundula
G
Notheis
Bernd
B
Buchholz
Arndt
A
Borkhardt
Jennifer
J
Neubert
D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D005858:Germany; D015658:HIV Infections / Q000151:congenital* / Q000188:drug therapy / Q000235:genetics* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification*; D059866:HLA-DQ beta-Chains / Q000235:genetics*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D019713:Receptors, CCR5 / Q000235:genetics*; D011795:Surveys and Questionnaires
D044966:Anti-Retroviral Agents; C584933:CCR5 protein, human; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D019713:Receptors, CCR5