Rising HIV-1 viral load set point at a population level coincides with a fading impact of host genetic factors on HIV-1 control.
| Autor: | van Manen D; Department of Experimental Immunology, Sanquin Research, Landsteiner Laboratory, Center for Infectious Diseases and Immunity Amsterdam at the Academic Medical Center of the University of Amsterdam, The Netherlands., Gras L, Boeser-Nunnink BD, van Sighem AI, Maurer I, Mangas Ruiz MM, Harskamp AM, Steingrover R, Prins JM, de Wolf F, van 't Wout AB, Schuitemaker H |
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| Jazyk: | angličtina |
| Zdroj: | AIDS (London, England) [AIDS] 2011 Nov 28; Vol. 25 (18), pp. 2217-26. |
| DOI: | 10.1097/QAD.0b013e32834bec9c |
| Abstrakt: | Objective: Heterozygosity for a 32 base pair deletion in the CCR5 gene (CCR5wt/Δ32) and the minor alleles of a single-nucleotide polymorphism in the HCP5 gene (rs2395029) and in the HLA-C gene region (-35HLA-C; rs9264942) has been associated with a lower viral load set point. Recent studies have shown that over calendar time, viral load set point has significantly increased at a population level. Here we studied whether this increase coincides with a fading impact of above-mentioned host genetic markers on HIV-1 control. Methods: We compared the association between viral load set point and HCP5 rs2395029, -35HLA-C rs9264942, and the CCR5wt/Δ32 genotype in HIV-1-infected individuals in the Netherlands who had seroconverted between 1982 and 2002 (pre-2003 seroconverters, n = 459) or between 2003 and 2009 (post-2003 seroconverters, n = 231). Results: Viral load set point in post-2003 seroconverters was significantly higher than in pre-2003 seroconverters (P = 4.5 × 10(-5)). The minor alleles for HCP5 rs2395029, -35HLA-C rs9264942 and CCR5wt/Δ32 had a similar prevalence in both groups and were all individually associated with a significantly lower viral load set point in pre-2003 seroconverters. In post-2003 seroconverters, this association was no longer observed for HCP5 rs2395029 and CCR5wt/Δ32. The association between viral load set point and HCP5 rs2395029 had significantly changed over time, whereas the change in impact of the CCR5wt/Δ32 genotype over calendar time was not independent from the other markers under study. Conclusion: The increased viral load set point at a population level coincides with a lost impact of certain host genetic factors on HIV-1 control. (2011 Wolters Kluwer Health | Lippincott Williams & Wilkins) |
| Databáze: | MEDLINE |
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