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

AIDS. 2014 Feb 20;28(4):543-7. doi: 10.1097/QAD.0000000000000065.

Abstract

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.

MeSH terms

  • Anti-Retroviral Agents / therapeutic use*
  • Child
  • Child, Preschool
  • Female
  • Genetic Predisposition to Disease*
  • Germany
  • HIV Infections / congenital*
  • HIV Infections / drug therapy
  • HIV Infections / genetics*
  • HIV Infections / virology
  • HIV-1 / isolation & purification*
  • HLA-DQ beta-Chains / genetics*
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Receptors, CCR5 / genetics*
  • Surveys and Questionnaires

Substances

  • Anti-Retroviral Agents
  • CCR5 protein, human
  • HLA-DQ beta-Chains
  • HLA-DQB1 antigen
  • Receptors, CCR5