CMV co‐infection and risk of AIDS and non‐AIDS events in a large cohort of HIV‐infected patients
Authors: Lichtner M , Cicconi P , Vita S , Cozzi‐Lepri A , Galli M , Lo Caputo S , Angarano G , De Luca A , Moioli F , Maggiolo F , Marchetti G , Vullo V , d'Arminio Monforte A ,   Icona Foundation Study
Published: November 2012

In HIV‐positive patients (pts), CMV co‐infection has been proposed as a key factor in sustaining immune activation, which in turn could play a role in determining immune senescence. We evaluated the prevalence and predictors of CMV co‐infection in a cohort of HIV+ pts and assessed the impact of CMV co‐infection on the risk of AIDS and non‐AIDS events. We included pts in the ICONA study with<1 month follow‐up and<1 CMVIgG (CMV) test available without active CMV disease. Pts' characteristics at time of the first CMV test (baseline) were compared in those tested positive (CMV+) and negative (CMV‐) using X2/Wilcoxon tests. Factors associated with CMV+ were identified by logistic regression. A prospective analysis was also performed with endpoints AIDS/AIDS‐related death and severe non‐AIDS (SNA: cardio‐cerebrovascular, neurologic disease, renal failure, non‐AIDS tumours)/death due to SNA. Time to event was estimated by Kaplan‐Meier curves and Cox regression (multivariable model included: age, gender, ethnicity, risk factor for HIV, HCVAb and HBsAg, AIDS and CD4 at baseline, initiation of ART prior to baseline). 6,053 pts were included; 83.7% were tested CMV+ a median of 17 (IQR 6–45) months after enrolment. As compared to CMV‐, CMV+ were older (adjusted odds ratio (AOR) 1.03 per 1 year older [95% CI 1.02–1.04]), HIV infected by homosexual route (MSM) (AOR 1.39 [95% CI 1.06–1.82]), less frequently Caucasian (AOR 0.56 [95% CI 0.42–0.76]), with higher CD4 count at baseline (AOR per 1 cell higher 1.035 [95% CI 1.00–1.06] By 10 years from first CMV test, 402 (12.6% [95% CI 11.1–13.6]) CMV+ and 74 (10.1% [95% CI 7.7–12.5]) CMV‐ pts developed AIDS/AIDS‐related death (log‐rank p=0.43). After adjustment for potential confounders, CMV+was still not associated with the risk of AIDS/AIDS‐related death (adjusted hazard ratio (AHR) 1.23 [95% CI 0.96–1.60]). By 10 years, 339 (10.6% [95% CI 9.4–11.9]) CMV+ and 41 (6.4% [95% CI 6.1–6.6]) CMV‐ pts experienced a non‐AIDS event/non‐AIDS death (log‐rank p=0.0006): 151 cancers, 128 CVD, 33 neurological, 1 renal. The association was still significant after controlling for a number of potential confounders: AHR 1.77 [95% CI 1.25–2.51] p=0.001; Table). In our study population, CMV/HIV co‐infection was associated with the risk of non‐AIDS events/deaths independently of other prognostic factors, supporting a potential role of CMV infection in vascular/ degenerative organ disorders commonly associated with chronic immune activation and aging.

Characteristic
AHR
95% CI
p‐value

CMVIgg+vs. CMVIgg−
1.77
1.25–2.51
0.001

Age, per 10 years older
1.64
1.46–1.84
0.0001

Female vs. male
1.43
1.12–1.83
0.004

Caucasian vs. Other
0.64
0.40–1.02
0.06

Homosexuals vs. IVDU
0.84
0.55–1.28
0.42

Heterosexuals vs. IVDU
0.87
0.60–1.26
0.47

HCVAb+vs. HCVAb−
1.28
0.92–1.78
0.13

HBsAg+vs HBsAg−
1.05
0.67–1.62
0.83

AIDS at baseline
0.94
0.67–1.32
0.75

CD4/µL at baseline per 100 cells/µL higher
0.97
0.93–1.01
0.16

HIV‐RNA at baseline per log10 cp/mL higher
1.05
0.96–1.16
0.26

Years from HIV diagnosis per 5 years longer
1.02
0.90–1.17
0.69

ART experienced vs. naïve at baseline
0.94
0.66–1.36
0.77