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

Abstract

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.

Keywords: cancers; immune recovery; non–AIDS-defining cancers; people with HIV; virological suppression.