Mortality and Non-Fatal Clinical Outcomes After the Most Common Cancers in People with HIV: A Multicohort Collaboration

Background/Objectives: Whilst cancer is a leading cause of death in people with HIV, less is known about clinical outcomes after cancer. Methods: Participants from the RESPOND and D:A:D cohorts with the five most common cancers (Kaposi's sarcoma (KS); non-Hodgkin lymphoma (NHL); and lung, anal and prostate cancers) were followed from first cancer diagnosis after 2006/2012 [D:A:D/RESPOND] until death, final follow-up or administrative censoring (2016/2021). Incidence rates (IR) were calculated for post-cancer mortality; for non-fatal events (cardiovascular disease, diabetes, another primary cancer, AIDS events) individually and as a non-fatal composite clinical outcome (CCO). Predictors or mortality and CCO were assessed using Poisson regression with generalized estimating equations. Results: Amongst 2485 participants with cancer, mortality and CCO IRs were highest after lung cancer (445.4/1000 person years [95% CI 399.7, 494.9], 117.1 [94.3, 143.8], respectively) compared to other cancers and lowest after KS (21.3 [16.9, 26.6], 43.9 [37.5, 51.3]). The most common non-fatal outcomes were AIDS events after NHL and KS, diabetes after lung and prostate cancer and another primary cancer after anal cancer. Among people with NHL and anal cancer, a diagnosis in more recent years was associated with lower mortality risk. Increasing the time-updated CD4 count reduced mortality by 15-40% (per 100 cells/µL) after NHL and anal and lung cancers and reduced CCO risk by 17-28% after KS and NHL. Smoking, low BMI and multimorbidity increased CCO risks by two to three times after KS and NHL. Conclusions: Risk of post-cancer mortality and non-fatal outcomes varies by cancer type and risk profile, suggesting the need for personalized post-cancer clinical monitoring.