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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 A, De Spiegelaere W, Cozzi-Lepri A, Kiselinova M, Pollakis G, Beloukas A, Vandekerckhove L, Strain M, Richman D, Phillips A, Geretti AM, ERAS Study Gro - EBioMedicine (2015)

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Infection, Microbiology and Immunology (CIMI), Institute of Infection and Global Health (IGH), University of Liverpool, 8 West Derby Street, Liverpool L697BE, United Kingdom.

ABSTRACT

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 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).

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.

No MeSH data available.


Related in: MedlinePlus

Correlation between integrated HIV-1 DNA load and a) total HIV-1 DNA load, b) residual plasma HIV-1 RNA levels, c) 2-LTR circular HIV-1 DNA levels, d) frequency of CD8+HLA-DR/DP/DQ+ cells, e) frequency of CD8+CD38+ cells, and f) levels of sCD14. Scatter plots with predicted HIV-1 DNA by the fitted fractional polynomial curves (with 95% confidence interval) and Spearman's rho (with p values) are shown.
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f0005: Correlation between integrated HIV-1 DNA load and a) total HIV-1 DNA load, b) residual plasma HIV-1 RNA levels, c) 2-LTR circular HIV-1 DNA levels, d) frequency of CD8+HLA-DR/DP/DQ+ cells, e) frequency of CD8+CD38+ cells, and f) levels of sCD14. Scatter plots with predicted HIV-1 DNA by the fitted fractional polynomial curves (with 95% confidence interval) and Spearman's rho (with p values) are shown.

Mentions: Integrated HIV-1 DNA load was positively correlated with total HIV-1 DNA load (p < 0.0001), frequency of CD8+HLA-DR/DP/DQ+ cells (p = 0.01), and sCD14 levels (p = 0.04), but not with the levels of residual plasma HIV-1 RNA (p = 0.81) and 2-LTR circular HIV-1 DNA (p = 0.50), or the frequency of CD8+CD38+ cells (p = 0.33) (Fig. 1). The associations were also tested by univariate and multivariable linear regression analysis (Table 4). A first model was built including pre-ART viral load, duration of suppressive ART, CD4 cell counts, residual plasma HIV-1 RNA levels, frequency of CD8+HLA-DR/DP/DQ+ cells, and sCD14 levels. In this adjusted model, integrated HIV-1 DNA load was a mean of 0.5 log10 copies higher for each 50% increment in the frequency of CD8+HLA-DR/DP/DQ+ cells (95% CI 0.2, 0.9; p = 0.01) (Table 4).


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 A, De Spiegelaere W, Cozzi-Lepri A, Kiselinova M, Pollakis G, Beloukas A, Vandekerckhove L, Strain M, Richman D, Phillips A, Geretti AM, ERAS Study Gro - EBioMedicine (2015)

Correlation between integrated HIV-1 DNA load and a) total HIV-1 DNA load, b) residual plasma HIV-1 RNA levels, c) 2-LTR circular HIV-1 DNA levels, d) frequency of CD8+HLA-DR/DP/DQ+ cells, e) frequency of CD8+CD38+ cells, and f) levels of sCD14. Scatter plots with predicted HIV-1 DNA by the fitted fractional polynomial curves (with 95% confidence interval) and Spearman's rho (with p values) are shown.
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4588402&req=5

f0005: Correlation between integrated HIV-1 DNA load and a) total HIV-1 DNA load, b) residual plasma HIV-1 RNA levels, c) 2-LTR circular HIV-1 DNA levels, d) frequency of CD8+HLA-DR/DP/DQ+ cells, e) frequency of CD8+CD38+ cells, and f) levels of sCD14. Scatter plots with predicted HIV-1 DNA by the fitted fractional polynomial curves (with 95% confidence interval) and Spearman's rho (with p values) are shown.
Mentions: Integrated HIV-1 DNA load was positively correlated with total HIV-1 DNA load (p < 0.0001), frequency of CD8+HLA-DR/DP/DQ+ cells (p = 0.01), and sCD14 levels (p = 0.04), but not with the levels of residual plasma HIV-1 RNA (p = 0.81) and 2-LTR circular HIV-1 DNA (p = 0.50), or the frequency of CD8+CD38+ cells (p = 0.33) (Fig. 1). The associations were also tested by univariate and multivariable linear regression analysis (Table 4). A first model was built including pre-ART viral load, duration of suppressive ART, CD4 cell counts, residual plasma HIV-1 RNA levels, frequency of CD8+HLA-DR/DP/DQ+ cells, and sCD14 levels. In this adjusted model, integrated HIV-1 DNA load was a mean of 0.5 log10 copies higher for each 50% increment in the frequency of CD8+HLA-DR/DP/DQ+ cells (95% CI 0.2, 0.9; p = 0.01) (Table 4).

Bottom Line: 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).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.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Infection, Microbiology and Immunology (CIMI), Institute of Infection and Global Health (IGH), University of Liverpool, 8 West Derby Street, Liverpool L697BE, United Kingdom.

ABSTRACT

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 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).

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.

No MeSH data available.


Related in: MedlinePlus