Risk of cancer in people with HIV experiencing varying degrees of immune recovery with sustained virological suppression on antiretroviral treatment for more than 2 years: An International, Multicenter, Observational Cohort

Background. The impact of long-term virological suppression (VS) and CD4 count recovery on non–AIDS-defining cancers (NADCs) is unclear. We determined whether poor immune recovery was associated with incident cancer risk in people with human immunodeficiency virus (HIV) with VS. Methods. Participants from the Data-Collection on Adverse Effects of Anti-HIV Drugs (D:A:D) and International Cohort Consortium of Infectious Disease (RESPOND) collaborations in Europe and Australia who achieved ≥2 years of VS on antiretroviral therapy (ART) between December 1999 and December 2022 were included. Follow-up was from baseline (date of VS for 2 years) until the earliest of a first cancer event, virological failure, final follow-up, or administrative censoring date. Multivariable Poisson regression was used to assess associations between cancer incidence (overall, AIDS-defining cancer, NADC, infection-related cancer, infection-unrelated cancer) and time-updated CD4 count stratified by pre-ART nadir CD4 counts. Results. Overall, 48 343 people with VS were included (median [interquartile range] baseline age, 43 years [37–50]; CD4 count, 540 cells/µL [380–730]; nadir CD4 count, 245 cells/µL [121–394]; 74% male). There were 1933 incident cancers (median follow-up, 6.2 years [2.9–9.5]; incidence rate [IR], 6.43; 95% confidence interval [CI]: 6.15–6.73/1000 person-years). Higher time-updated CD4 count was associated with a reduced risk of overall cancer (adjusted incidence rate ratio for time-updated CD4 count 350–499 cells/ µL: 0.45 [95% CI: 0.39–0.51]; 500–749 cells/µL: 0.30 [95% CI: 0.27–0.34]; and ≥750 cells/µL: 0.26 [95% CI: 0.23–0.30] vs <350 cells/ µL; P < .0001). There was a significant reduction in all cancer risk by higher time-updated CD4 count, regardless of nadir CD4 count, with higher pre-ART nadir CD4 count exhibiting lower risk. Conclusions. Despite VS on ART for more than 2 years, people with poorer immune recovery experienced a significantly higher incidence of cancer. This highlights the importance of early HIV diagnosis and ART initiation, and appropriate cancer screening strategies for those with poor immune recovery.