During Stably Suppressive Antiretroviral Therapy Integrated HIV-1 DNA Load in Peripheral Blood is Associated with the Frequency of CD8 Cells Expressing HLA-DR/DP/DQ

作者：Ruggiero Alessandra; De Spiegelaere Ward; Cozzi Lepri Alessandro; Kiselinova Maja; Pollakis Georgios; Beloukas Apostolos; Vandekerckhove Linos; Strain Matthew; Richman Douglas; Phillips Andrew; Geretti Anna Maria^*

来源：EBioMedicine, 2015, 2(9): 1153-1159.

DOI：10.1016/j.ebiom.2015.07.025

• Suppression
• Reservoir
• Persistence
• Integration
• Activation

Background: Characterising the correlates of HIV persistence improves understanding of disease pathogenesis and guides the design of curative strategies. This study investigated factors associated with integrated HIV-1 DNA load during consistently suppressive first-line antiretroviral therapy (ART).
Method: Total, integrated, and 2-long terminal repeats (LTR) circular HIV-1 DNA, residual plasma HIV-1 RNA, T-cell activation markers, and soluble CD14 (sCD14) were measured in peripheral blood of 50 patients that had received 1-14 years of efavirenz-based or nevirapine-based therapy.
Results: Integrated HIV-1 DNA load (per 106 peripheral blood mononuclear cells) was median 1.9 log(10) copies (interquartile range 1.7-2.2) and showed a mean difference of 0.2 log(10) copies per 10 years of suppressive ART (95% confidence interval -0.2, 0.6; p = 0.28). It was positively correlated with total HIV-1 DNA load and frequency of CD8(+) HLA-DR/DP/DQ(+) cells, and was also higher in subjects with higher sCD14 levels, but showed no correlation with levels of 2-LTR circular HIV-1 DNA and residual plasma HIV-1 RNA, or the frequency of CD4(+) CD38(+) and CD8(+) CD38(+) cells. Adjusting for pre-ART viral load, duration of suppressive ART, CD4 cell counts, residual plasma HIV-1 RNA levels, and sCD14 levels, integrated HIV-1 DNA load was mean 0.5 log(10) copies higher for each 50% higher frequency of CD8(+) HLA-DR/DP/DQ(+) cells (95% confidence interval 0.2, 0.9; p= 0.01).
Conclusions: The observed positive association between integrated HIV-1 DNA load and frequency of CD8(+) DR/DP/DQ(+) cells indicates that a close correlation between HIV persistence and immune activation continues during consistently suppressive therapy. The inducers of the distinct activation profile warrant further investigation.

• 出版日期2015-9