Virologic and host characteristics of human immunodeficiency virus type 1-infected pediatric long term survivors

Abstract

Background: There are limited data concerning determinants of varying clinical progression rates in human immunodeficiency virus type 1 (HIV-1)-infected children. Therefore, we sought to determine whether viral or host factors associated with nonprogressive HIV-1 infection in adults play a role in limiting progression of infection in 5 vertically infected youths, ages 12-18 years, who have displayed no signs of advanced HIV-1 disease or acquired immunodeficiency syndrome despite having received minimal treatment with antiretroviral drugs.

Results: The 5 individuals, whom we characterize as long term survivors, have maintained low loads of HIV-1 RNA in plasma when compared to many of their peers, and have also maintained normal and stable CD4 T-lymphocyte numbers and percentages throughout their lives. Determination of their predominant HIV-1 sequences revealed that 4 of 5 patients harbor virus with markers of resistance to their therapy (one was never treated). Furthermore 2 harbored viral isolates that contained insertions in Gag or Vif that inhibit HIV-1 replication. Moreover, 2 were found to be heterozygous for the CCR2 polymorphism 64I, a genotype associated with slower progression to acquired immunodeficiency syndrome in adults. All 5 expressed the histocompatibility leukocyte antigen DQ1 and 2 had unusual DR/DQ1 phenotypes.

Conclusions: We believe that the limited antiretroviral therapy received by the long term survivors cannot solely account for their benign clinical status. Therefore, we conclude that other factors, including gene polymorphisms that affect viral replicative capacity, account for the long term survival in some, and deduce that, as in adults, no single factor (virologic or host) can account for this clinical phenotype in all cases.