Decreased HIV type 1 transcription in CCR5-Δ32 heterozygotes during suppressive antiretroviral therapy

抑制性抗逆转录病毒疗法期间 CCR5-Δ32 杂合子中的 HIV 1 型转录降低

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作者:Charlene Wang, Mohamed Abdel-Mohsen, Matthew C Strain, Steven M Lada, Steven Yukl, Leslie R Cockerham, Christopher D Pilcher, Frederick M Hecht, Elizabeth Sinclair, Teri Liegler, Douglas D Richman, Steven G Deeks, Satish K Pillai

Abstract

Individuals who are heterozygous for the CCR5-Δ32 mutation provide a natural model to examine the effects of reduced CCR5 expression on human immunodeficiency virus (HIV) persistence. We evaluated the HIV reservoir in 18 CCR5-Δ32 heterozygotes and 54 CCR5 wild-type individuals during suppressive antiretroviral therapy. Cell-associated HIV RNA levels (P=.035), RNA to DNA transcriptional ratios (P=.013), and frequency of detectable HIV 2-long terminal repeat circular DNA (P=.013) were significantly lower in CD4+ T cells from CCR5-Δ32 heterozygotes. Cell-associated HIV RNA was significantly correlated with CCR5 surface expression on CD4+ T cells (r2=0.136; P=.002). Our findings suggest that curative strategies should further explore manipulation of CCR5.

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