Inflammation strongly signals CV events in treated female vs male HIV patients

For HIV patients treated with antiretroviral therapy (ART), higher levels of inflammatory biomarkers help predict non-AIDS cardiovascular (CV) events more strongly in women than men, according to a study.

Presented at the virtual Conference on Retroviruses and Opportunistic Infections (CROI) 2021 by study author Dr Samuel Schnittman from the University of California San Francisco, the findings may partially explain why HIV-infected women are at higher cardiovascular risk than their male peers, even though the female sex has been associated with a more favourable risk of non-AIDS morbidities.

The sex-related discrepancy in the levels of immune activation in ART-treated patients may be driven by the effects of sex hormones as well as host genetics, he noted.

There are cases where systemic inflammation persists even after successful ART, and this predicts both non-AIDS events and mortality, according to Schnittman. However, the specific biologic pathways that mediate these events as well as the influence of sex-related differences in inflammation on outcomes are yet unclear, and the desire to define these had been their reason for conducting the study.

The analysis included 979 patients (median age, 47 years; 82 percent male) who maintained ART-induced viral suppression for at least 1 year and had available plasma samples. There were 76 type 1 myocardial infarction (MI), 56 type 2 MI, 30 ischaemic stroke, 80 venous thromboembolism (VTE), and 70 deaths documented in the cohort over 3–5 years of follow-up.

Schnittman and his colleagues examined the impact of 13 common inflammation biomarkers found that individual markers predicted distinct events. For instance, elevated levels of C-reactive protein (CRP), soluble CD14 (sCD14), and soluble tumour necrosis factor receptor 2 (sTNFR2) were associated with up to 1.6-fold increased T1MI risk (p<0.01). Meanwhile, higher concentrations of CRP, soluble urokinase-type plasminogen activator receptor (suPAR), and intercellular adhesion molecule (ICAM-1) correlated with up to 1.7-fold increased VTE risk (p<0.01). [CROI 2021, abstract 98]

CRP also predicted venous thromboembolism and mortality but not type 2 MI nor ischaemic stroke, whereas ICAM-1 was linked to type 2 MI and mortality but not the other three outcomes.

Notably, 11 inflammation markers were expressed at significantly higher levels in women. Further analysis indicated that sex could modify associations between inflammation and a vascular event, such that specific inflammatory markers more strongly predicted the corresponding vascular events in women than men. On the other hand, the association of distinct markers with VTE tended to be stronger in men.

Schnittman acknowledged that their analysis may be limited by scant data on transgender participants and sex hormone therapy, as well as plasma sex hormones. Nevertheless, he believes that their data drive home the importance of identifying “specific inflammatory signatures driving discrete disease entities” and developing “pragmatic surrogates.”

Additionally, the REPRIEVE and ACTG A5383 trials may shed light on the impact of statins and the anti-cytomegalovirus drug letermovir (MK-8228) on the observed interactions, he said. [Am Heart J 2019;212:23-35; N Engl J Med 2017;377:2433-2444]