Table S1 Relative hazard of clinical progression from fitting a Cox proportional hazard regression model according to alternative analysis i) – all patients.
Crude and adjusted relative hazards of clinical progression
Biomarker Crude RH (95% CI) p-value AdjustedMRH (95% CI) p-value AdjustedMMRH (95% CI) p-value a) biomarkers fitted as categorical variables
IL-6, pg/ml
<¼1 1.0 1.0 1.0
>1 0.85 (0.60, 1.20) 0.346 1.06 (0.74, 1.50) 0.765 1.08 (0.74, 1.58) 0.694
not measured 0.81 (0.50, 1.29) 0.370 0.94 (0.58, 1.52) 0.798 1.01 (0.37, 2.79) 0.981
LPS, pg/ml
<¼110 1.0 1.0 1.0
>110 1.87 (1.27, 2.76) 0.002 1.79 (1.20, 2.68) 0.004 1.69 (1.11, 2.58) 0.014
not measured 0.91 (0.61, 1.35) 0.631 0.82 (0.54, 1.23) 0.335 0.70 (0.43, 1.14) 0.149
sCD14,mg/ml
<¼3 1.0 1.0 1.0
>3 1.38 (0.97, 1.96) 0.073 1.32 (0.92, 1.89) 0.132 1.30 (0.90, 1.89) 0.164
not measured 1.20 (0.73, 1.97) 0.479 1.08 (0.65, 1.79) 0.771 1.13 (0.37, 3.40) 0.830
TNF-alfa, pg/ml
<¼2.5 1.0 1.0 1.0
>2.5 1.38 (0.96, 1.98) 0.078 1.29 (0.89, 1.85) 0.173 1.27 (0.87, 1.86) 0.211
not measured 1.46 (0.95, 2.24) 0.088 1.29 (0.83, 2.00) 0.255 1.65 (0.83, 3.26) 0.151
Patients were grouped according to whether their value of the biomarker was above or below the median.MAll models (a separate one for each biomarker) adjusted forage, CD4, VL, HCV/HBV, year of test, duration of HIV infection at the date of the test
MMFurther mutually adjusted for all biomarkers.
b) biomarkers fitted as continuous variables in the logescale IL-6, pg/ml
per logehigher 0.90 (0.78, 1.03) 0.124 0.94 (0.80, 1.09) 0.400 0.93 (0.73, 1.17) 0.528 LPS, pg/ml
per logehigher 1.37 (1.15, 1.64) <.001 1.40 (1.16, 1.69) <.001 1.45 (1.19, 1.77) <.001 sCD14,mg/ml
per logehigher 1.32 (0.98, 1.77) 0.069 1.14 (0.84, 1.55) 0.392 1.09 (0.73, 1.63) 0.658 TNF-alfa, pg/ml
per logehigher 1.41 (1.03, 1.93) 0.034 1.25 (0.90, 1.74) 0.187 1.23 (0.81, 1.86) 0.329
MAll models (a separate one for each biomarker) adjusted forage, CD4, VL, HCV/HBV, year of test, duration of HIV infection at the date of the test
MMFurther mutually adjusted for all biomarkers.
Table S2 Relative hazard of clinical progression from fitting a Cox proportional hazard regression model according alternative analysis ii) – all patients.
Crude and adjusted relative hazards of clinical progression
Biomarker Crude RH (95% CI) p-value AdjustedMRH (95% CI) p-value AdjustedMMRH (95% CI) p-value a) biomarkers fitted as categorical variables
IL-6, pg/ml
<¼1 1.0 1.0 1.0
>1 0.71 (0.38, 1.31) 0.268 1.00 (0.53, 1.89) 0.991 0.97 (0.48, 1.93) 0.923
not measured 0.55 (0.22, 1.36) 0.198 0.98 (0.38, 2.50) 0.966 0.67 (0.06, 6.97) 0.739
LPS, pg/ml
<¼110 1.0 1.0 1.0
>110 1.44 (0.70, 2.97) 0.321 1.18 (0.55, 2.56) 0.669 1.04 (0.47, 2.33) 0.919
not measured 0.70 (0.35, 1.40) 0.313 0.68 (0.33, 1.40) 0.299 0.54 (0.23, 1.29) 0.165
sCD14,mg/ml
<¼3 1.0 1.0 1.0
>3 1.62 (0.86, 3.06) 0.138 1.63 (0.85, 3.13) 0.140 1.68 (0.85, 3.34) 0.136
not measured 1.05 (0.41, 2.72) 0.916 1.40 (0.53, 3.69) 0.492 1.79 (0.21, 15.44) 0.595
TNF-alfa, pg/ml
<¼2.5 1.0 1.0 1.0
>2.5 1.83 (0.97, 3.43) 0.061 1.99 (1.02, 3.88) 0.044 2.24 (1.10, 4.55) 0.026
not measured 1.35 (0.59, 3.09) 0.472 1.63 (0.70, 3.76) 0.257 2.45 (0.60, 9.97) 0.210
Patients were grouped according to whether their value of the biomarker was above or below the median.MAll models (a separate one for each biomarker) adjusted forage, CD4, VL, HCV/HBV, year of test, duration of HIV infection at the date of the test
MMFurther mutually adjusted for all biomarkers.
b) biomarkers fitted as continuous variables in the logescale IL-6, pg/ml
per logehigher 0.89 (0.64, 1.23) 0.486 0.99 (0.68, 1.44) 0.961 0.93 (0.58, 1.50) 0.762 LPS, pg/ml
per logehigher 1.23 (0.83, 1.85) 0.305 1.18 (0.77, 1.82) 0.439 1.16 (0.74, 1.82) 0.515 sCD14,mg/ml
per logehigher 2.13 (1.19, 3.84) 0.011 1.78 (0.99, 3.21) 0.054 2.00 (0.86, 4.69) 0.109 TNF-alfa, pg/ml
per logehigher 1.88 (1.07, 3.30) 0.027 1.86 (0.96, 3.59) 0.064 2.37 (0.96, 5.85) 0.062
MAll models (a separate one for each biomarker) adjusted forage, CD4, VL, HCV/HBV, year of test, duration of HIV infection at the date of the test
MMFurther mutually adjusted for all biomarkers.
Table S3 Relative hazard of clinical progression from fitting a Cox proportional hazard regression model according to main analysis – patients with baseline CD4 count >300 cells/ml.
Crude and adjusted relative hazards of clinical progression
Biomarker Crude RH (95% CI) p-value AdjustedMRH (95% CI) p-value AdjustedMMRH (95% CI) p-value a) biomarkers fitted as categorical variables
IL-6, pg/ml
<¼1 1.0 1.0 1.0
>1 0.86 (0.64, 1.14) 0.282 1.02 (0.77, 1.36) 0.888 1.02 (0.75, 1.39) 0.898
not measured 1.01 (0.71, 1.43) 0.959 1.20 (0.83, 1.72) 0.329 1.19 (0.53, 2.65) 0.671
LPS, pg/ml
<¼110 1.0 1.0 1.0
>110 1.89 (1.37, 2.63) <.001 1.79 (1.28, 2.51) <.001 1.73 (1.22, 2.46) 0.002
not measured 1.29 (0.94, 1.76) 0.111 1.18 (0.86, 1.62) 0.309 1.00 (0.68, 1.47) 0.991
sCD14,mg/ml
<¼3 1.0 1.0 1.0
>3 1.28 (0.96, 1.70) 0.091 1.12 (0.84, 1.50) 0.442 1.12 (0.83, 1.52) 0.442
not measured 1.34 (0.93, 1.94) 0.119 1.25 (0.86, 1.83) 0.242 1.03 (0.43, 2.47) 0.956
TNF-alfa, pg/ml
<¼2.5 1.0 1.0 1.0
>2.5 1.27 (0.94, 1.70) 0.114 1.14 (0.85, 1.54) 0.379 1.11 (0.81, 1.51) 0.521
not measured 1.49 (1.07, 2.07) 0.018 1.37 (0.98, 1.92) 0.065 1.32 (0.74, 2.36) 0.351
Patients were grouped according to whether their value of the biomarker was above or below the median.MAll models (a separate one for each biomarker) adjusted forage, CD4, VL, HCV/HBV, year of test, duration of HIV infection at the date of the test
MMFurther mutually adjusted for all biomarkers.
b) biomarkers fitted as continuous variables in the logescale IL-6, pg/ml
per logehigher 0.86 (0.75, 1.00) 0.044 0.89 (0.76, 1.04) 0.147 0.89 (0.73, 1.09) 0.259 LPS, pg/ml
per logehigher 1.38 (1.18, 1.61) <.001 1.34 (1.14, 1.58) <.001 1.37 (1.14, 1.64) <.001 sCD14,mg/ml
per logehigher 1.34 (1.02, 1.76) 0.033 1.12 (0.85, 1.48) 0.436 1.32 (0.90, 1.94) 0.154 TNF-alfa, pg/ml
per logehigher 1.36 (1.04, 1.77) 0.023 1.22 (0.92, 1.61) 0.172 1.16 (0.81, 1.68) 0.422
MAll models (a separate one for each biomarker) adjusted forage, CD4, VL, HCV/HBV, year of test, duration of HIV infection at the date of the test
MMFurther mutually adjusted for all biomarkers.
Table S4 Relative hazard of clinical progression from fitting a Cox proportional hazard regression model according to main analysis restricted to 140 patients after controlling for parameters of T-cell activation (i.e. CD8þCD38þ, CD8þHLA-DRþ).
Crude and adjusted relative hazards of clinical progression
Biomarker Crude RH (95% CI) p-value AdjustedMRH (95% CI) p-value AdjustedMMRH (95% CI) p-value a) biomarkers fitted as categorical variables
CD8þCD38þ, %
<¼70 1.0 1.0 1.0
>70 0.80 (0.53, 1.19) 0.265 0.87 (0.58, 1.30) 0.500 0.84 (0.51, 1.36) 0.473
not measured 0.70 (0.50, 1.00) 0.047 0.67 (0.47, 0.96) 0.027 0.73 (0.48, 1.09) 0.124
IL-6, pg/ml
<¼1 1.0 1.0 1.0
>1 0.91 (0.69, 1.20) 0.507 1.12 (0.85, 1.47) 0.436 1.07 (0.79, 1.44) 0.670
not measured 1.03 (0.74, 1.45) 0.858 1.28 (0.91, 1.82) 0.157 1.41 (0.66, 3.03) 0.374
LPS, pg/ml
<¼110 1.0 1.0 1.0
>110 1.90 (1.39, 2.60) <.001 1.92 (1.39, 2.66) <.001 1.93 (1.38, 2.70) <.001
not measured 1.31 (0.97, 1.76) 0.077 1.32 (0.97, 1.79) 0.077 1.21 (0.83, 1.75) 0.318
sCD14,mg/ml
<¼3 1.0 1.0 1.0
>3 1.32 (1.00, 1.74) 0.046 1.12 (0.84, 1.48) 0.439 1.11 (0.83, 1.49) 0.486
not measured 1.35 (0.95, 1.93) 0.098 1.28 (0.89, 1.84) 0.183 1.00 (0.43, 2.34) 0.995
TNF-alfa, pg/ml
<¼2.5 1.0 1.0 1.0
>2.5 1.36 (1.03, 1.80) 0.033 1.22 (0.92, 1.62) 0.170 1.14 (0.85, 1.54) 0.383
not measured 1.54 (1.12, 2.11) 0.008 1.43 (1.04, 1.98) 0.028 1.16 (0.65, 2.06) 0.615
HLA-DR, pg/ml
<¼50 1.0 1.0 1.0
>50 0.93 (0.62, 1.40) 0.733 1.02 (0.68, 1.54) 0.925 1.26 (0.77, 2.08) 0.356
not measured 0.78 (0.54, 1.11) 0.161 0.74 (0.51, 1.06) 0.103 0.73 (0.48, 1.09) 0.124
MAll models (a separate one for each biomarker) adjusted forage, CD4, VL, HCV/HBV, year of test, duration of HIV infection at the date of the test.
MMFurther mutually adjusted for all biomarkers.
b) biomarkers fitted as continuous variables in the logescale CD8þCD38þ, %
per logehigher 0.93 (0.32, 2.70) 0.891 0.87 (0.29, 2.57) 0.798 1.02 (0.19, 5.52) 0.979 IL-6, pg/ml
per logehigher 0.90 (0.78, 1.03) 0.124 0.94 (0.80, 1.09) 0.400 0.70 (0.53, 0.93) 0.013 LPS, pg/ml
per logehigher 1.38 (1.20, 1.60) <.001 1.37 (1.18, 1.60) <.001 1.37 (0.95, 1.97) 0.090 sCD14,mg/ml
per logehigher 1.41 (1.10, 1.82) 0.007 1.15 (0.89, 1.49) 0.287 1.22 (0.67, 2.22) 0.507 TNF-alfa, pg/ml
per logehigher 1.44 (1.12, 1.85) 0.005 1.24 (0.95, 1.61) 0.122 1.27 (0.75, 2.15) 0.379 HLA-DR, pg/ml
per logehigher 0.97 (0.76, 1.24) 0.829 0.99 (0.76, 1.29) 0.952 0.85 (0.55, 1.33) 0.485
MAll models (a separate one for each biomarker) adjusted forage, CD4, VL, HCV/HBV, year of test, duration of HIV infection at the date of the test.
MMFurther mutually adjusted for all biomarkers.