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


Ruggiero, Alessandra, De Spiegelaere, Ward, Cozzi-Lepri, Alessandro, Kiselinova, Maja, Pollakis, Georgios ORCID: 0000-0002-9659-5461, Beloukas, Apostolos ORCID: 0000-0001-5639-0528, Vandekerckhove, Linos, Strain, Matthew, Richman, Douglas, Phillips, Andrew et al (show 1 more authors) (2015) 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. EBIOMEDICINE, 2 (9). pp. 1153-1159.

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Abstract

<h4>Background</h4>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).<h4>Method</h4>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.<h4>Results</h4>Integrated HIV-1 DNA load (per 10(6) peripheral blood mononuclear cells) was median 1.9 log10 copies (interquartile range 1.7-2.2) and showed a mean difference of 0.2 log10 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 log10 copies higher for each 50% higher frequency of CD8(+)HLA-DR/DP/DQ(+) cells (95% confidence interval 0.2, 0.9; p = 0.01).<h4>Conclusions</h4>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.

Item Type: Article
Uncontrolled Keywords: Suppression, Reservoir, Persistence, Integration, Activation
Depositing User: Symplectic Admin
Date Deposited: 14 Oct 2015 08:55
Last Modified: 16 Dec 2022 01:26
DOI: 10.1016/j.ebiom.2015.07.025
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/2031561
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