Supplementary Table 1.Patients characteristics

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.

2Age at cohort registration was missing in 345 patients (68 among patients at risk to develop CMV retinitis).

3Median maximal HIV RNA load was missing in 39 patients (4 among patients at risk to develop CMV retinitis).

4Median CD4 slope was missing in 551 patients (11 among patients at risk to develop CMV retinitis).

5HCV co-infection was missing in 119 patients (16 among patients at risk to develop CMV retinitis).

6Active HBV infection was missing in 206 patients (41 among patients at risk to develop CMV retinitis).

7CMV 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).

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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
IFNL3/4rs368234815
(-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.

Stepwise (i.e. backward) regression (P<0.2) was used to determine which variables were independently associated with the endpoint.

1The 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)

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Supplementary Table 3.Association between CMV retinitis and rs368234815using 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.

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