Inflammation predicts vascular disease in treated HIV, with ‘important’ sex differences
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There are distinct inflammatory pathways that predict vascular disease in patients being treated for HIV, according to study results presented at the Conference on Retroviruses and Opportunistic Infections.
Researchers also uncovered “important biological sex differences” in the study of almost 1,000 people, including that women with HIV had higher levels of inflammation than men with HIV, and that inflammation “tended to predict several diseases more so in women than in men,” said Samuel Schnittman, MD, a research fellow in the department of medicine at the University of California, San Francisco.
“Our study adds to the knowledge of the specific inflammatory pathways that predict vascular diseases,” Schnittman told Healio. “Ultimately, we need a clinical trial that proves that an intervention reduces disease.”
Schnittman and colleagues assessed a random subset of 979 patients with HIV after 1 year of ART who had available blood plasma and all patients (also suppressed for 1 year or more) who had a diagnosis of type 1 or 2MI (T1MI, T2MI) ischemic stroke or venous thromboembolism (VTE). They analyzed the relationship between plasma biomarkers and sex and the risk for these events.
Of the patients, 76 had T1MI, 56 had T2MI, 30 had ischemic stroke, 80 had VTE, and 70 died. Women had a 1.3 to 2.7 fold interquartile range (IQR) higher C-reactive protein (CRP) and a total of 11 out of 13 inflammatory markers measured compared to men (P < .04), and the differences were even larger among older women. Higher CRP, IL-6, LPS-binding protein (LBP), kynurenine-to-tryptophan (KT) ratio, suPAR, sTNFR1, and CMV IgG titer were associated with T1MI (P < .03). Higher CRP, IL-6, LBP, suPAR, sTNFR1, and CMV IgG titer were associated with VTE (P < .03). Virtually all biomarkers were associated with a greater hazard of T2MI and death.
Overall, biomarkers tended to be associated with cardiovascular disease more often in women than in men, but the opposite effect was seen with VTE events where the biomarkers were more strongly predictive in men than in women, which Schnittman said may be related to the sex hormone’s effects on clotting.
“We need an ‘atlas’ of pathways that predict specific diseases for rational clinical trial design, and this study contributes to this goal,” Schnittman said.
Schnittman said the study also highlights that inflammation is an “important problem for women, particularly postmenopausal women with treated HIV.”
“While more men than women are living with HIV in the United States, globally, more women than men have HIV,” he said. “Yet women in general tend to be underrepresented in clinical trials of immune-based interventions. Our field simply needs to do a better job of enrolling women in clinical trials.”
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Schnittman SR, et al. Abstract 98. Presented at: Conference on Retroviruses and Opportunistic Infections; March 6-10, 2021 (virtual meeting).
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