Despite cancer being a leading comorbidity amongst individuals with HIV, there are limited data assessing cancer trends across different antiretroviral therapy (ART)-eras. We calculated age-standardised cancer incidence rates (IRs) from 2006–2021 in two international cohort collaborations (D:A:D and RESPOND). Poisson regression was used to assess temporal trends, adjusted for potential confounders. Amongst 64,937 individuals (31% ART-naïve at baseline) and 490,376 total person-years of follow-up (PYFU), there were 3763 incident cancers (IR 7.7/1000 PYFU [95% CI 7.4, 7.9]): 950 AIDS-defining cancers (ADCs), 2813 non-ADCs, 1677 infection-related cancers, 1372 smoking-related cancers, and 719 BMI-related cancers (groups were not mutually exclusive). Age-standardised IRs for overall cancer remained fairly constant over time (8.22/1000 PYFU [7.52, 8.97] in 2006–2007, 7.54 [6.59, 8.59] in 2020–2021). The incidence of ADCs (3.23 [2.79, 3.72], 0.99 [0.67, 1.42]) and infection-related cancers (4.83 [4.2, 5.41], 2.43 [1.90, 3.05]) decreased over time, whilst the incidence of non-ADCs (4.99 [4.44, 5.58], 6.55 [5.67, 7.53]), smoking-related cancers (2.38 [2.01, 2.79], 3.25 [2.63–3.96]), and BMI-related cancers (1.07 [0.83, 1.37], 1.88 [1.42, 2.44]) increased. Trends were similar after adjusting for demographics, comorbidities, HIV-related factors, and ART use. These results highlight the need for better prevention strategies to reduce the incidence of NADCs, smoking-, and BMI-related cancers.

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.