Intracellular HIV-1 RNA and CD4+ T-cell activation in patients starting antiretrovirals. (19th June 2017) - El-Diwany, Ramy
Abstract : Objective: To assess if the reduction in HIV-1 RNA in CD4 + T cells is correlated with the persistence of immune activation following early antiretroviral therapy (ART). Design: Clinical trial (NCT01285050). Methods: Next-generation sequencing was used to study total RNA from activated CD4 + T cells (CD38 and human leukocyte antigen - antigen D related (HLA-DR) expressing) collected from 19 treatment-naïve HIV-1/hepatitis C virus-infected patients before and early after ART initiation (≥12 weeks after plasma HIV-1 RNA <50 copies/ml). To validate comparisons, pre and post-ART measures were adjusted for input RNA and overall read number. Results: As expected, ART use was associated with a median [interquartile range (IQR)] 4.3% (2.2–8.3) reduction in the proportion of activated CD4 + T cells ( P = 0.0008). Whereas in those activated CD4 + T cells no consistent differences in overall gene expression were detected, interferon-stimulated gene expression declined ( P < 2 × 10 −16 ). Pre-ART, sorted activated CD4 + T cells contained a median (IQR) of 959 (252–1614) HIV-1 reads/10 7 reads compared with 72 (55–152) HIV-1 reads/10 7 reads after at least 12 weeks of suppressive ART ( P = 8 × 10 −5 ). The decrease in HIV-1 reads in activated CD4 + T cells was associated with the change in plasma HIV-1 RNA levels ( r = 0.77, P = 2 × 10 −4 ) and the change in the proportion of activated CD4 + T cells ( r = 0.70, P = 0.0016). Conclusion: Months of ART led to a marked decrease in cell-associated HIV-1 RNA and interferon-stimulated genes expression in activated CD4 + T cells that were strongly associated with the reduction in the proportion of activated CD4 + T cells. Abstract : Supplemental Digital Content is available in the text