Elite Controllers and Longterm Nonprogressors A Possible Role for Host Genes

Although most individuals infected with HIV eventually develop AIDS, approximately 1% of individuals who are infected do not develop disease. Such individuals have high CD4+ and CD8+ T cell counts, do not require therapy, and have persistent viremia but no disease for at least 10 to 15 years. On the basis of the degree of viremia, this group can be divided into two subsets: long-term non-progressors have detectable viremia of around 5000 copies of HIV-1 RNA per milliliter of blood; and a much smaller subset of "elite controllers" present with viral loads of about 50 copies or less of HIV-1 RNA per milliliter of blood. There is considerable interest in understanding the genetic basis of HIV control by examining these cohorts of individuals in detail. So far, a strong role for the MHC locus in protecting individuals and preventing progression has been suggested by genetic association studies. Specific HLA class I and even some HLA class II loci have been linked to the absence of disease progression. We have previously mentioned the importance of the inheritance of the CCR5 homozygous 32-bp deletion in protection from infection, and other genetic factors contributing to resistance are likely to be revealed in the coming years.

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