CMV associated with 50% increased risk of non-AIDS related mortality in HIV positive people

Coinfection with cytomegalovirus (CMV) infection may be associated with a 50% higher risk of non-AIDS defining mortality compared to HIV people who are CMV negative, according to an analysis from Italian ICONA cohort study, published in the January edition of JID. [1]

Miriam Lichtner and colleagues at Sapienza University of Rome, Italy, investigated patients from the Italian multi-centre, prospective observational ICONA Foundation Study cohort, who were naïve to ART at enrolment. Lichtner et al assessed clinical events and causes of death in a subset of 6,111 patients who had had at least one CMV IgG antibody test and had at least one follow up visit since their CMV test. Patients who had any reported CMV-related disease or non-AIDS-defining event were excluded from the study analysis.

CMV antibodies were detected in 5119 study participants (83.3%). In multivariable logistic analysis, being CMV positive was associated (adjusted odds ratio) with age per 10 year increase (aOR 1.42; 95%CI: 1.33 – 1.52, p<0.0001), MSM sex vs IV drug use (aOR 1.67; 95%CI: 1.36 – 2.06, p=0.0001) and a higher CD4 count at baseline (aOR 1.04; 95%CI: 1.02 – 1.06, p = 0.0005). Being CMV positive was negatively associated with white ethnicity (aOR, 0.51; 95%CI: 0.39 – 0.66, p=0.001).

During a median 5.2 years of follow up, 413 participants experienced an AIDS-defining event and 77 died as a result of an AIDS-related disease. No significant differences were seen in the frequency of AIDS-defining events or AIDS-related deaths between CMV-seropositive and CMV negative individuals.

In contrast, severe non-AIDS defining events or non-AIDS related deaths were significantly related to CMV coinfection. During a median 5.6 years of follow up, 326 patients experienced severe non-AIDS defining events and 12 patients died from non-AIDS related diseases. The investigators estimated the proportion of patients reaching either end point at 10 years as 6.2% (95%CI: 4.1% – 8.3%) for CMV seronegative patients and 8.9% (95%CI: 7.7% – 10.1%) for CMV seropositive patients (p = 0.0058). Even after controlling for a number of potential confounding factors (including age, sex, ethnicity, HCV or HBV status, mode of HIV transmission, time from HIV diagnosis, CDC disease stage, use of ART, CD4 count or CD4/CD8 T cell ratio), being CMV positive remained an independent risk factor for severe non-AIDS defining events or non-AIDS related deaths (adjusted hazard ratio [HR] 1.53 995% CI, 1.08 – 2.16, p=0.16).

In multivariate analysis, being CMV positive was not associated with non-AIDS related malignancies or nonvascular neurological diseases. In contrast, CMV positivity was an independent risk factor for cardiovascular and cerebrovascular diseases (adjusted HR, 2.27 [95% CI, 0.97 – 5.32, p=0.058).

The authors concluded that CMV infection might play a significant role in the non-AIDS related morbidity and mortality of HIV positive people. There was a striking association between being CMV positive and risk of cardiovascular and cerebrovascular disease. There is increasing evidence that inflammatory processes may play a role in these diseases and CMV has been directly implicated in cardiovascular disease such as atherosclerosis. It is therefore possible that subclinical CMV activity may contribute to the inflammation-mediated pathology of vascular disease in people with long-term HIV infection.

Comment

The mechanism for any association remains unclear as recent HIV studies looking at this potential therapeutic role of anti-inflammatory drugs have not shown clinical benefits.

Lichtner M et al. Cytomegalovirus co-infection is associated with an increased risk of severe non-AIDS defining events in a large cohort of HIV-infected patients. JID (2015) Jan 15;211(2):178-86. doi: 10.1093/infdis/jiu417.
http://www.ncbi.nlm.nih.gov/pubmed/25081936