BACKGROUND: CXCR4-using virus is associated with higher viral load and accelerated human immunodeficiency virus (HIV) disease progression. Additionally, CCR5 antagonists may not reduce the HIV-1 RNA load when mixed/dual-tropic or CXCR4-using virus is present. The determination of coreceptor tropism may be required before CCR5 or CXCR4 antagonists are initiated, unless reliable predictive markers of coreceptor use are established. METHODS: Samples from treatment-naive and -experienced HIV-1-positive individuals with date-matched CD4 and CD8 cell counts and HIV-1 RNA, clade, and pol sequences were assessed for coreceptor usage, by use of the ViroLogic PhenoSense assay. RESULTS: Coreceptor use determination was successful in 563 of 861 samples. Non-clade B virus was present in 18.6% of samples. CXCR4 or mixed/dual-tropic CCR5/CXCR4 virus was present in 112 of samples (19.9%). Only 4 samples (0.7%) showed exclusive CXCR4 use. In a multivariate model, higher CD4 cell count, lower viral load, and higher natural killer cell counts were significantly associated with CCR5 usage. No associations with treatment experience, clade, or pol gene mutations were observed. CONCLUSION: The prevalence of CCR5-tropic HIV-1 phenotype declines with decreasing CD4 cell count and increasing viral load. Mixed/dual tropic virus is found in all CD4 cell count and viral load strata. Coreceptor usage is not influenced by viral clade.
BACKGROUND:CXCR4-using virus is associated with higher viral load and accelerated human immunodeficiency virus (HIV) disease progression. Additionally, CCR5 antagonists may not reduce the HIV-1 RNA load when mixed/dual-tropic or CXCR4-using virus is present. The determination of coreceptor tropism may be required before CCR5 or CXCR4 antagonists are initiated, unless reliable predictive markers of coreceptor use are established. METHODS: Samples from treatment-naive and -experienced HIV-1-positive individuals with date-matched CD4 and CD8 cell counts and HIV-1 RNA, clade, and pol sequences were assessed for coreceptor usage, by use of the ViroLogic PhenoSense assay. RESULTS: Coreceptor use determination was successful in 563 of 861 samples. Non-clade B virus was present in 18.6% of samples. CXCR4 or mixed/dual-tropic CCR5/CXCR4 virus was present in 112 of samples (19.9%). Only 4 samples (0.7%) showed exclusive CXCR4 use. In a multivariate model, higher CD4 cell count, lower viral load, and higher natural killer cell counts were significantly associated with CCR5 usage. No associations with treatment experience, clade, or pol gene mutations were observed. CONCLUSION: The prevalence of CCR5-tropic HIV-1 phenotype declines with decreasing CD4 cell count and increasing viral load. Mixed/dual tropic virus is found in all CD4 cell count and viral load strata. Coreceptor usage is not influenced by viral clade.
Authors: Jeffrey M Jacobson; Jacob P Lalezari; Melanie A Thompson; Carl J Fichtenbaum; Michael S Saag; Barry S Zingman; Paul D'Ambrosio; Nancy Stambler; Yakov Rotshteyn; Andre J Marozsan; Paul J Maddon; Stephen A Morris; William C Olson Journal: Antimicrob Agents Chemother Date: 2010-07-26 Impact factor: 5.191
Authors: Jessica D Church; Wei Huang; Anthony Mwatha; Philippa Musoke; J Brooks Jackson; Danstan Bagenda; Saad B Omer; Deborah Donnell; Clemensia Nakabiito; Chineta Eure; Laura A Guay; Allan Taylor; Paul M Bakaki; Flavia Matovu; Michelle McConnell; Mary Glenn Fowler; Susan H Eshleman Journal: Curr HIV Res Date: 2010-10 Impact factor: 1.581
Authors: Jeannette M Whitcomb; Wei Huang; Signe Fransen; Kay Limoli; Jonathan Toma; Terri Wrin; Colombe Chappey; Linda D B Kiss; Ellen E Paxinos; Christos J Petropoulos Journal: Antimicrob Agents Chemother Date: 2006-11-20 Impact factor: 5.191