For a study recently published in the Journal of Acquired Immune Deficiency Syndromes, my colleagues and I assessed the morbidity and mortality associated with a set of potentially life-threatening events (labeled grade 4 events) in people with HIV and how these events relate to inflammation. We defined grade 4 events to not include events traditionally considered as primary outcomes in HIV studies (eg, AIDS events, cardiovascular disease (CVD), and non-AIDS cancer). To examine these associations, we combined data from two large international HIV studies, SMART and ESPRIT, resulting in a set of 3,568 HIV-infected participants who were on suppressive antiretroviral therapy.

We found that grade 4 events were more common than AIDS, CVD, or non-AIDS cancer events, and that they were associated with a similar risk of death as AIDS events. We classified each grade 4 event as inflammatory or not, and found that nearly half of all participants with a grade 4 event had an inflammatory event. Additionally, higher levels of interleukin 6 and D-dimer were associated with an increased risk of grade 4 events overall; these associations grew stronger when only considering the inflammatory events.

Many grade 4 events appear to have a significant inflammatory component. Future research should seek to determine if treatments that reduce inflammatory biomarkers also lead to a reduced risk of inflammatory grade 4 events. Our findings suggest that such treatments might impact the risk of many conditions aside from AIDS, CVD, and non-AIDS cancer events. Confirmation of our findings could lead to more efficient trial designs of novel anti-inflammatory agents.