Supplementary Table 1. Patients characteristics
All
Patients at risk to develop CMV retinitis1
Proportion N=4884 N=1134
Male sex 3842 (0.79) 885 (0.78)
Median age (IQR)
At cohort registration2 37 (14) 37 (15)
At estimated date of infection 31 (14) 31 (14)
HIV risk factors
MSM 2299 (0.47) 491 (0.43)
Heterosexual 1467 (0.30) 362 (0.32)
Drug user 952 (0.19) 241 (0.21)
Other 166 (0.03) 40 (0.04)
Median CD4+ T cells nadir (per mm3, IQR) 171 (184) 39.5 (47) Median maximal HIV RNA (copies/ml, IQR)3 5.15 (0.91) 5.39 (0.80)
Median CD4 slope4 -2.11 (1.21) -2.66 (0.97)
HAART 4680 (0.96) 1128 (0.99)
HCV co-infection5 2244 (0.47) 619 (0.55)
Active HBV infection6 200 (0.04) 61 (0.06)
CMV positive serology7 3962 (0.83) 1134 (1.00)
CMV disease (other than retinitis) 48 (0.01) 31 (0.03)
CMV retinitis1 43 (0.01) 40 (0.04)
IFNL3/4 rs368234815, minor allele frequency 0.32 0.31
Values are the number and proportion of patients with indicated characteristics, unless otherwise indicated. MSM stands for male having sex with male; HAART, highly active antiretroviral therapy; HCV, hepatitis C virus; HBV, hepatitis B virus; CMV, cytomegalovirus; IQR, interquartile range.
1 Risk to develop CMV retinitis was defined by a positive CMV serology and a CD4 T cell nadir <100/mm3. Three patients with CMV retinitis who did not have an estimable date of infection were not included.
2 Age at cohort registration was missing in 345 patients (68 among patients at risk to develop CMV retinitis).
3 Median maximal HIV RNA load was missing in 39 patients (4 among patients at risk to develop CMV retinitis).
4 Median CD4 slope was missing in 551 patients (11 among patients at risk to develop CMV retinitis).
5 HCV co-infection was missing in 119 patients (16 among patients at risk to develop CMV retinitis).
6 Active HBV infection was missing in 206 patients (41 among patients at risk to develop CMV retinitis).
7 CMV serology was missing in 93 patients. There was no association between rs368234815 and CMV serostatus (CMV seropositivity 85% among -G-G carriers versus 82.3% among TT/TT or TT/-G patients, P=0.14).
1
Supplementary Table 2. Detailed statistical analyses.
Univariate
Model Multivariate model 1
(HAART included) Multivariate model 2 (HAART not included)
Variable HR (95% CI)
P sign.
Proport.
hazard P1 HR (95% CI)
P sign.
Proport.
hazard
P HR (95% CI)
P sign.
Proport.
hazard P Sex
0.72 (0.32-
1.64) 0.44 0.73
Age at estimated date of infection (continuous)
1.00 (0.97-
1.03) 0.99 0.09
CD4 nadir (sqrt transformed,
continuous) 0.71 (0.63-
0.81) <0.001 0.26 0.73 (0.64-
0.84) <0.001 0.15 0.70 (0.61-
0.80) <0. 001 0.17
CD4 slope (continuous)
0.64 (0.45-
0.92) 0.01 0.15
0.73 (0.49-
1.07) 0.11 0.17
Maximal HIV RNA load
(continuous) 1.38 (0.87-
2.17) 0.17 0.79
HAART
(time-dependant covariate)
0.48 (0.24-
0.97) 0.04 0.03
0.40 (0.18-
0.88) 0.02 0.04
Risk factors
MSM Ref. Ref. Ref.
Hetero
0.57 (0.27-
1.20) 0.14 0.65
0.51 (0.23-
1.09) 0.08 0.66
0.53 (0.25-
1.14) 0.10 0.75
Drug user
0.40 (0.15-
1.06) 0.06 0.68
0.35 (0.13-
0.93) 0.04 0.51
0.39 (0.15-
1.01) 0.053 0.64
other 0.53 (0.07-
3.93) 0.54 0.96
HCV co-infection
1.03 (0.55-
1.93) 0.92 0.75
Active HBV infection
0.88 (0.21-
3.63) 0.86 0.77
IFNL3/4 rs368234815 (-G/-G versus TT/TT or TT/- G)
2.59 (1.26-
5.29) 0.009 0.24
2.31 (1.09-
4.92) 0.03 0.22
2.53 (1.20-
5.35) 0.015 0.23
HR stands for hazard ratio; CI, confidence interval; MSM, male having sex with male; HAART, highly active antiretroviral therapy; HCV, hepatitis C virus; HBV, hepatitis B virus.
2
Stepwise (i.e. backward) regression (P<0.2) was used to determine which variables were independently associated with the endpoint.
1 The proportional hazard assumption was tested by using the stphtest command implemented in Stata. The global proportional hazard assumption test P value was 0.0515 for the first multivariate model (including HAART as a covariate) and 0.5 for the second multivariate model (without HAART)
3
Supplementary Table 3. Association between CMV retinitis and rs368234815 using different modes of inheritance
CMV retinitis
Mode of inheritance P*
rs368234815 Absent
(N=1094)
Present (N=40)
TT/TT 535 16 Additive 0.39
TT/-G 438 14 Dominant 0.27
-G/-G 121 10 Recessive 0.009
P values were calculated by using a logistic regression model by using the indicated mode of inheritance.
