Incidence and risk factors of HIV-related non-Hodgkin lymphoma in the era of combination antiretroviral therapy: European multi-cohort study

Background: Incidence and risk factors of HIV-associated non-Hodgkin lymphoma (NHL) are not well defined in the era of combination antiretroviral therapy (cART). Methods: 56,305 adult HIV-1 infected patients who started cART in one of 22 prospective studies in Europe were included. Weibull random-effects models were used to estimate hazard ratios (HRs) for developing systemic NHL, including CD4 cell counts and viral load as time-updated variables. Results: During 212,042 person-years of follow-up, 521 patients were diagnosed with systemic NHL and 62 with primary brain lymphoma (PBL). The incidence rate of systemic NHL was 463 per 100,000 person-years not on cART and 205 per 100,000 person-years in treated patients, for a rate ratio of 0.44 (95% confidence interval [CI] 0.37 to 0.53). The corresponding incidence rates of PBL were 57 and 24 per 100,000 person-years (rate ratio 0.43; 95% CI 0.25 to 0.73). Suppression of HIV-1 replication on cART (HR 0.60, 95% CI 0.44-0.81, comparing ≤500 with 10,000-99,999 viral copies/ml) and increases in CD4 counts (HR 0.30, 0.22-0.42, comparing ≥350 with 100-199 cells/μL) were protective; a history of Kaposi sarcoma (HR 1.70, 1.08-2.68, compared to no history of AIDS), transmission through sex between men (HR 1.57, 1.19-2.08, compared to heterosexual transmission) and older age (HR 3.72, 2.38-5.82, comparing >50 with 16-29 years) were risk factors for systemic NHL. Conclusions: The incidence rates of both systemic NHL and PBL are substantially reduced in patients on cART. Timely initiation of therapy is key to the prevention of NHL in the era of cART.