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CXCR4 or CCR5 tropism of human immunodeficiency virus type 1 isolates does not determine the immunological milieu in patients responding to antiretroviral therapy.

Price P, Keane N, Gray L, Lee S, Gorry PR, French MA

  • Journal Viral immunology

  • Published 28 Feb 2007

  • Volume 19

  • ISSUE 4

  • Pagination 734-40

  • DOI 10.1089/vim.2006.19.734


Here we address whether CCR5 or CXCR4 tropism of the predominant viral strain detected before or on combination antiretroviral therapy (ART) explains why some human immunodeficiency virus (HIV)-infected patients who begin ART with advanced HIV disease retain low interferon (IFN)-gamma responses, despite recovery of CD4(+) T cell counts. Tropism was determined by culture and confirmed by gp120 V3 loop sequence of multiple plasma samples in eight adult male patients who began treatment with <50 CD4(+) T cells/microL. Four patients had mixed infections, one had only R5 HIV, and three had only X4 HIV. Of these, two carried CCR5Delta32. Viral tropism was not related to CD4(+) T cell counts or HIV RNA levels. When immunological responses were monitored over several years, IFN-gamma responses to cytomegalovirus were below the median value of uninfected controls and similar in patients with R5, X4, or mixed infection. Interleukin-5 responses were low and plasma soluble CD30 levels were high at treatment onset, but resolved with control of HIV replication irrespective of HIV tropism. Levels of LAG-3 (lymphocyte activation gene-3 protein) were elevated in patients with uncontrolled HIV replication. Hence the immunological milieu did not reflect HIV tropism.