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 HIV reduces this risk while also adjusting for socio-economic status.

METHODS: We included individuals (≥18 years) from the Dutch national ATHENA cohort diagnosed with HIV-1 and having started ART between 2000-2022 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 socio-economic status (SES) using data from Statistics Netherlands.

RESULTS: Compared to 'late-ART' (n=17,965) participants, 'early-ART' participants (n=1,858) 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=0.40-0.91]) and infection-unrelated NADM (HR=0.60 [95%CI=0.37-0.98]), but not of infection-related NADM (HR=0.58 [95%CI=0.27-1.28]). Additional adjustment for SES only minimally changed the hazard ratios.

CONCLUSIONS: Starting ART within one year of HIV acquisition is associated with a reduced NADM risk compared to starting ART later.