Presented at CROI, investigators have identified sex-modified inflammatory predictors of cardiovascular and VTE risks among patients with HIV.
A team of investigators have observed that inflammation pathways distinctly modified by patient sex may help clinicians predict cardiovascular disease and venous thromboembolic (VTE) events in people with HIV.
The findings, presented at the Conference on Retroviruses and Opportunistic Infections (CROI) 2021 virtual sessions this week, could help investigator better discern particular cardiovascular risks among men versus women with HIV.
Presented by author Samuel R. Schnittman, MD, of the University of California San Francisco, the trial sought to interpret the treatment-resistant inflammation prevalent in patients with HIV. Specifically, events including VTE, myocardial infarction (MI), and ischemic stroke occur in different pathways, yet the sex-modified influence of such events in this patient population had not yet been fully defined.
The case-cohort assessment included a randomized sample of patients from the CFAR Network of Integrated Clinical Systems (CNICS) Network with available plasma after ≥1 year of antiretroviral therapy (ART)-mediated viral suppression of HIV. Eligible plasma samples additionally came from patients subsequently diagnosed with an incident type 1 or 2 MI (T1MI; T2MI), ischemic stroke, or VTE.
Composite cardiovascular disease events included T1MI and ischemic stroke. Schnittman and colleagues normalized the relationship between 11 plasma biomarkers to the cohort’s interquartile range (IQR).
Logistic regression was used to assess subsequent cardiovascular event risk among patients with ART-mediated viral suppression, with adjustments made for patient age, natal sex, nadir CD4, and confounders including smoking status, atherosclerotic cardiovascular disease (ASCVD) risk score, and history of hepatitis C virus.
The overall sub-cohort included 979 participants, featuring 103 cardiovascular events (75 T1MI; 30 ischemic stroke), 56 T2MI, and 80 VTE cases. Median patient age was 47 years old, with 82% being men, and 17% with a history of injection drug use (IDU).
Median risk for ASCVD risk was 4%, and median current and nadir CD4 were logged at 576 and 248, respectively.
Among a half-dozen observed inflammatory pathways, women reported a 1.4 – 2.5 fold greater IQR count than men (P <.03). Greater CRP, sCD14, and sTNFR2 levels were associated with up to 1.6-fold increased T1MI risk (P <.01). Greater CRP, suPAR, and ICAM-1 were associated with up to 1.7-fold increased VTE risk (P <.01).
All but 3 biomarkers (CRP, LBP, and CMV IgG) were linked to increased incident T2MI risk (P <.001).
Schnittman and colleagues noted that inflammatory markers generally were more strongly associated with cardiovascular events in women versus men, while men were at greater risk of inflammatory-associated VTE events.
“Nevertheless, it has remained unclear whether these sex-based differences in inflammation have clinical consequences in treating HIV,” Schnittman said in his presentation of the data at CROI. “Several studies have shown that the female advantage in cardiovascular disease risk is attenuated in HIV.”
Their findings, that immune activation may be greater in women and more linked with event risks, may explain this known association.
“As inflammation predicts CVD events more strongly in women than in men, representation of women in clinical studies of immune-based interventions in treated HIV infection is critical,” investigators concluded.