Data on cancer incidence and associated risk factors among women with HIV are limited. We investigated cancer burden among women with HIV. We included all women ≥18 years from the two large multicentre observational cohort collaborations (D:A:D and RESPOND). The primary outcomes were incidence of all cancers, HPV-related and common individual cancers including breast cancer, lung cancer, and non-Hodgkin lymphoma (NHL) from 2006 to 2021. Baseline was defined as the latest date of entry into local cohort enrolment and 1st January 2006 for D:A:D and 1st January 2012 for RESPOND. Participants were followed from baseline until the date of first cancer, final follow-up or administrative censoring—whichever occurred first. We assessed risk factors using multivariable Poisson regression by applying robust standard errors and determined a population attributable fraction (PAF) for key risk factors for cancers. Among 17,512 women included, median age at baseline was 39.5 years (interquartile range, IQR 32.5–46.0). Over 141,404 person-years (PYS) and a median 9.2 (5.5–10.1) years of follow-up, 832 women were diagnosed with any cancer; incidence rate 5.9 (95% CI 5.5–6.4)/1000 PYS, 163 HPV-related cancers (1.1 [1.0–1.3]/1000 PYS), 150 breast cancers (1.1 [0.9–1.2]/1000 PYS), 94 lung cancers (0.7 [0.5–0.8]/1000 PYS) and 72 NHL (0.5 [0.4–0.6]/1000 PYS). Older age (≥45 vs. <45 years), Southern Europe (vs. Western Europe) and smoking were associated with an increased risk of overall cancers. Lower pre-ART nadir CD4, time-updated CD4, and a prior AIDS diagnosis were associated with lung- and HPV-related cancer. In PAF analysis, smoking and HIV-related factors such as lower current CD4, nadir CD4 and HIV viremia significantly contributed to cancer risk. Our findings suggest that women with HIV older than 45 years, past or current immunosuppressed or current smokers could be candidates for intensified cancer screening and prevention. The Highly Active Antiretroviral Therapy Oversight Committee, The CHU St Pierre Brussels HIV Cohort, The Austrian HIV Cohort Study, The Australian HIV Observational Database, The AIDS Therapy Evaluation in the Netherlands national observational HIV cohort, The Brighton HIV Cohort, The National Croatian HIV Cohort, The EuroSIDA cohort, The Frankfurt HIV Cohort Study, The Georgian National AIDS Health Information System, The Nice HIV Cohort, The 10.13039/100025411 Isabel Foundation , The Modena HIV Cohort, The PISCIS Cohort Study, The Swiss HIV Cohort Study, The Swedish InfCare HIV Cohort, The Royal Free HIV Cohort Study, The San Raffaele Scientific Institute, The University Hospital Bonn HIV Cohort, The University of Cologne HIV Cohort, Merck Life Sciences, 10.13039/100010877 ViiV Healthcare , and Gilead Sciences.

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.

Objective: Whilst cancer is increasingly common in people with HIV, insight into immunological outcomes after cancer diagnosis (CaD) is limited. European guidelines recommend opportunistic infection prophylaxis (OIP) at CD4 ⁺ cell count of less than 200 cells/μl, and during chemotherapy/radiotherapy regardless of CD4 ⁺ cell count. We assessed CD4 ⁺ cell count trends and predictors of post-CaD immunosuppression across common cancers. Design: Participants from D:A:D and RESPOND with Kaposi's sarcoma, non-Hodgkin lymphoma (NHL), lung, anal or prostate cancer and at least two CD4 ⁺ cell count measurements at 6–12 months post-CaD were included. Methods: CD4 ⁺ cell count measurements were evaluated at 6-monthly intervals. Logistic regression models with generalized estimating equations assessed predictors of CD4 ⁺ cell count of less than 200 up to 3 years post-CaD. Results: Among 1670 individuals (9597 person-years of follow-up, median 5.3 years), 89% were male, median age was 51 years [interquartile range (IQR) 42–60] and median CD4 ⁺ cell count of 400 cells/μl (288–590) at CaD. The highest proportion of participants with CD4 ⁺ cell count of less than 200 cells/μl was at time of CaD for Kaposi's sarcoma (36%), at 6 months post-CaD for NHL and anal cancer (40% and 30% respectively), at 12 months post-CaD for lung (17%) and 18 months post-CaD for prostate cancer (7%). Higher CD4 ⁺ cell count at CaD was associated with lower odds of CD4 ⁺ cell count of less than 200 post-CaD [200–350: 0.12 (95% confidence interval 0.08–0.16); 350–500: 0.05 (0.03–0.07); >500: 0.02 (0.02–0.04), vs. <200]. Other predictors included disseminated disease, anal cancer, injection drug use as HIV acquisition mode and male gender/sex; age and calendar time were not predictive. Conclusion: As post-CaD immunosuppression trends varied by several factors including cancer type, and CD4 ⁺ cell count at CaD, individualized use of opportunistic infection prophylaxis may be considered when regular CD4 ⁺ cell count monitoring is available.