I calculated the intra-network and inter-network signatures in order to look for differences between HIV+ well-controlled, HIV + uncontrolled, and HIV- individuals. Here are their compositions:

These cohorts aren’t particularly well matched, so we will control for differences in age, sex, and education throughout the analysis.

##                                    Stratified by Group
##                                     Control          UnControlled     
##   n                                    224               117          
##   Group (%)                                                           
##      Control                           224 (100.0)         0 (  0.0)  
##      UnControlled                        0 (  0.0)       117 (100.0)  
##      WellControlled                      0 (  0.0)         0 (  0.0)  
##   participant_age (mean (sd))        37.83 (17.15)     39.80 (16.76)  
##   gender_check = 1 (%)                 115 ( 51.3)        23 ( 19.7)  
##   blood_pressure (mean (sd))        119.07 (15.49)    122.66 (15.42)  
##   race (%)                                                            
##      1                                   2 (  0.9)         1 (  0.9)  
##      2                                   0 (  0.0)         1 (  0.9)  
##      4                                   4 (  1.8)         1 (  0.9)  
##      7                                 116 ( 51.8)        81 ( 69.2)  
##      8                                 102 ( 45.5)        33 ( 28.2)  
##      9                                   0 (  0.0)         0 (  0.0)  
##   education (mean (sd))             460.20 (6680.54)   13.09 (2.20)   
##   bmi (mean (sd))                    26.87 (5.82)      25.95 (6.30)   
##   duration_of_infection (mean (sd))   0.00 (0.00)      87.83 (99.69)  
##   recent_cd4 (mean (sd))               NaN (NA)       408.12 (305.48) 
##   nadir_cd4 (mean (sd))                NaN (NA)       245.58 (204.90) 
##   recent_viral_load (mean (sd))        NaN (NA)      1461.11 (2384.83)
##   recent_cd8 (mean (sd))               NaN (NA)       872.00 (417.40) 
##   Hepatitis_A = 1 (%)                    1 (  0.4)         4 (  3.4)  
##   Hepatitis_B = 1 (%)                    0 (  0.0)         1 (  0.9)  
##   Hepatitis_C = 1 (%)                    0 (  0.0)         5 (  4.3)  
##                                    Stratified by Group
##                                     WellControlled   p      test
##   n                                    310                      
##   Group (%)                                          <0.001     
##      Control                             0 (  0.0)              
##      UnControlled                        0 (  0.0)              
##      WellControlled                    310 (100.0)              
##   participant_age (mean (sd))        48.03 (14.33)   <0.001     
##   gender_check = 1 (%)                  85 ( 27.4)   <0.001     
##   blood_pressure (mean (sd))        123.19 (13.57)    0.054     
##   race (%)                                            0.005     
##      1                                   4 (  1.3)              
##      2                                   1 (  0.3)              
##      4                                   0 (  0.0)              
##      7                                 209 ( 67.4)              
##      8                                  95 ( 30.6)              
##      9                                   1 (  0.3)              
##   education (mean (sd))             336.86 (5687.99)  0.777     
##   bmi (mean (sd))                    26.74 (5.81)     0.367     
##   duration_of_infection (mean (sd)) 162.56 (108.65)  <0.001     
##   recent_cd4 (mean (sd))            644.98 (297.76)  <0.001     
##   nadir_cd4 (mean (sd))             230.31 (206.76)   0.544     
##   recent_viral_load (mean (sd))      21.87 (5.97)    <0.001     
##   recent_cd8 (mean (sd))            852.74 (390.70)   0.876     
##   Hepatitis_A = 1 (%)                   25 (  8.1)   <0.001     
##   Hepatitis_B = 1 (%)                   38 ( 12.3)   <0.001     
##   Hepatitis_C = 1 (%)                   23 (  7.4)   <0.001

Analysis

For all subsequent analysis, the figures show the uncorrected p value where we do not control for age/sex/education. The blocks of text show the anova and subsequent Tukey’s HSD level test to look for differences in group. These values are corrected for differences in age/sex/educaion, as well as for the fact that we make 3 comparisons.

There is a significant difference between Well-controlled and uncontrolled individuals in Intra-network signature (but weirdly not between our healthy controls and either well- or poorly controlled individuals).

##                  Df Sum Sq Mean Sq F value   Pr(>F)    
## Group             2   30.8    15.4   6.000  0.00262 ** 
## gender_check      1   99.5    99.5  38.804 8.46e-10 ***
## participant_age   1  570.5   570.5 222.524  < 2e-16 ***
## education         1    0.2     0.2   0.074  0.78597    
## Residuals       644 1651.0     2.6                     
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
##   Tukey multiple comparisons of means
##     95% family-wise confidence level
## 
## Fit: aov(formula = Intra_Signature ~ Group + gender_check + participant_age + education, data = df.now)
## 
## $Group
##                                   diff         lwr       upr     p adj
## UnControlled-Control        -0.3209899 -0.75003324 0.1080534 0.1849092
## WellControlled-Control       0.2652537 -0.06481264 0.5953200 0.1429920
## WellControlled-UnControlled  0.5862436  0.17794916 0.9945381 0.0022708

There is also a significant difference between well controlled and poorly controlled individuals in the global inter-network signature; however, there is no difference between HIV+ individuals of any categorization and healthy controls.

##                  Df Sum Sq Mean Sq F value   Pr(>F)    
## Group             2     84    41.8   3.282  0.03818 *  
## gender_check      1    121   120.8   9.495  0.00215 ** 
## participant_age   1    348   348.2  27.369 2.28e-07 ***
## education         1      2     1.6   0.125  0.72395    
## Residuals       644   8194    12.7                     
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
##   Tukey multiple comparisons of means
##     95% family-wise confidence level
## 
## Fit: aov(formula = Inter_Signature ~ Group + gender_check + participant_age + education, data = df.now)
## 
## $Group
##                                   diff         lwr       upr     p adj
## UnControlled-Control        -0.8046994 -1.76050333 0.1511045 0.1185301
## WellControlled-Control       0.1801879 -0.55511950 0.9154952 0.8331662
## WellControlled-UnControlled  0.9848873  0.07530669 1.8944679 0.0300885

There’s no difference in DMN x DMN

##                  Df Sum Sq Mean Sq F value   Pr(>F)    
## Group             2    1.7    0.83   0.906  0.40446    
## gender_check      1    7.1    7.13   7.780  0.00544 ** 
## participant_age   1   47.8   47.80  52.156 1.45e-12 ***
## education         1    0.5    0.52   0.566  0.45218    
## Residuals       644  590.3    0.92                     
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
##   Tukey multiple comparisons of means
##     95% family-wise confidence level
## 
## Fit: aov(formula = DMN_x_DMN ~ Group + gender_check + participant_age + education, data = df.now)
## 
## $Group
##                                    diff        lwr       upr     p adj
## UnControlled-Control         0.08581745 -0.1707193 0.3423542 0.7118768
## WellControlled-Control      -0.05276768 -0.2501234 0.1445881 0.8047296
## WellControlled-UnControlled -0.13858513 -0.3827156 0.1055454 0.3770593

There’s no difference in DANxDAN.

##                  Df Sum Sq Mean Sq F value   Pr(>F)    
## Group             2    2.2   1.087   1.139  0.32073    
## gender_check      1    8.3   8.329   8.726  0.00325 ** 
## participant_age   1   27.9  27.931  29.262 8.92e-08 ***
## education         1    0.4   0.437   0.458  0.49874    
## Residuals       644  614.7   0.955                     
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
##   Tukey multiple comparisons of means
##     95% family-wise confidence level
## 
## Fit: aov(formula = DAN_x_DAN ~ Group + gender_check + participant_age + education, data = df.now)
## 
## $Group
##                                     diff        lwr        upr     p adj
## UnControlled-Control         0.144573010 -0.1172233 0.40636934 0.3972096
## WellControlled-Control      -0.009605131 -0.2110071 0.19179681 0.9931041
## WellControlled-UnControlled -0.154178141 -0.4033138 0.09495754 0.3140955

There’s no significant difference in SM x SM, although there is a trend to suggest that uncontrolled individuals have worse connectivity than either healthy controls or well-controlled individuals.

##                  Df Sum Sq Mean Sq F value   Pr(>F)    
## Group             2    5.3    2.63   2.777   0.0630 .  
## gender_check      1   33.7   33.69  35.588 4.02e-09 ***
## participant_age   1    3.9    3.94   4.157   0.0419 *  
## education         1    0.0    0.00   0.000   0.9849    
## Residuals       644  609.7    0.95                     
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
##   Tukey multiple comparisons of means
##     95% family-wise confidence level
## 
## Fit: aov(formula = SM_x_SM ~ Group + gender_check + participant_age + education, data = df.now)
## 
## $Group
##                                    diff         lwr        upr     p adj
## UnControlled-Control         0.24617359 -0.01455534 0.50690252 0.0689178
## WellControlled-Control       0.02362942 -0.17695136 0.22421021 0.9586645
## WellControlled-UnControlled -0.22254416 -0.47066407 0.02557574 0.0891955

There’s no difference in SM lat x SM lat.

##                  Df Sum Sq Mean Sq F value   Pr(>F)    
## Group             2    3.5    1.73   2.017 0.133845    
## gender_check      1   10.9   10.91  12.724 0.000388 ***
## participant_age   1   74.7   74.70  87.160  < 2e-16 ***
## education         1    0.0    0.00   0.001 0.975038    
## Residuals       644  552.0    0.86                     
## ---
## Signif. codes:  0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
##   Tukey multiple comparisons of means
##     95% family-wise confidence level
## 
## Fit: aov(formula = SM_lat_x_SM_lat ~ Group + gender_check + participant_age + education, data = df.now)
## 
## $Group
##                                    diff        lwr        upr     p adj
## UnControlled-Control         0.01528718 -0.2327851 0.26335945 0.9885133
## WellControlled-Control      -0.14043002 -0.3312739 0.05041389 0.1952965
## WellControlled-UnControlled -0.15571720 -0.3917925 0.08035812 0.2685975