Earlier Initiation of Treatment Following HIV Acquisition Reduces Non-AIDS-defining Malignancy Risk

Background: Starting antiretroviral treatment (ART) at higher CD4 cell counts is associated with reduced non-AIDS-defining malignancy (NADM) risk. We studied whether starting ART within 1 year after acquiring human immunodeficiency virus type 1 (HIV-1) reduces this risk while also adjusting for socioeconomic status. Methods: We included individuals (≥18 years) from the Dutch national ATHENA cohort diagnosed with human immunodeficiency virus (HIV) and having started ART between 2000 and 2022 without prior NADM with ≥6 months of follow-up. “Early ART” initiators were defined as starting ART <365 days following a negative HIV test or primary HIV infection, all others as “late-ART” starters. Hazard ratios (HR) for NADM were estimated using Cox regression, adjusted for a priori selected confounders (age, sex at birth, smoking, alcohol use, calendar time, HIV transmission route, region of origin, nadir CD4 cell count, HIV-1 viral copy-years), and socioeconomic status (SES) using data from Statistics Netherlands. Results: Compared to “late-ART” (n = 17 965) participants, “early-ART” participants (n = 1858) were younger (median 34.8 vs 39.0 years), with a higher nadir CD4 count (median 478 vs 260 cells/µL). NADM were diagnosed in 25 “early-ART” and 869 “late-ART” starters resulting in an incidence rate of 2.22/1000 person-years (PY) (95% confidence interval [CI] = 1.50–3.28) and 4.87/1000 PY (95% CI = 4.56–5.21), respectively. “Early-ART” initiation was associated with a reduced risk of any NADM (HR = 0.60 [95% CI = .40–.91]) and infection-unrelated NADM (HR = 0.60 [95% CI = .37–.98]), but not of infection-related NADM (HR = 0.58 [95% CI = .27–1.28]). Additional adjustment for SES only minimally changed the hazard ratios. Conclusions: Starting ART within 1 year of HIV acquisition is associated with a reduced NADM risk compared to starting ART later.