Risk for Non-AIDS-Defining and AIDS-Defining Cancer of Early Versus Delayed Initiation of Antiretroviral Therapy : A Multinational Prospective Cohort Study.

Chammartin, Frédérique; Lodi, Sara; Logan, Roger; Ryom, Lene; Mocroft, Amanda; Kirk, Ole; d'Arminio Monforte, Antonella; Reiss, Peter; Phillips, Andrew; El-Sadr, Wafaa; Hatleberg, Camilla I; Pradier, Christian; Bonnet, Fabrice; Law, Matthew; De Wit, Stéphane; Sabin, Caroline; Lundgren, Jens D; Bucher, Heiner C

BACKGROUND Immediate initiation of antiretroviral therapy (ART) regardless of CD4 cell count reduces risk for AIDS and non-AIDS-related events in asymptomatic, HIV-positive persons and is the standard of care. However, most HIV-positive persons initiate ART when their CD4 count decreases below 500 × 109 cells/L. Consequences of delayed ART on risk for non-AIDS-defining and AIDS-defining cancer, one of the most common reasons for death in HIV, are unclear. OBJECTIVE To estimate the long-term risk difference for cancer with the immediate ART strategy. DESIGN Multinational prospective cohort study. SETTING The D:A:D (Data collection on Adverse events of anti-HIV Drugs) study, which included HIV-positive persons from Europe, Australia, and the United States. PARTICIPANTS 8318 HIV-positive persons with at least 1 measurement each of CD4 cell count and viral load while ART-naive (study period, 2006 to 2016). MEASUREMENTS The parametric g-formula was used, with adjustment for baseline and time-dependent confounders (CD4 cell count and viral load), to assess the 10-year risk for non-AIDS-defining and AIDS-defining cancer of immediate versus deferred (at CD4 counts <350 and <500 × 109 cells/L) ART initiation strategies. RESULTS During 64 021 person-years of follow-up, 231 cases of non-AIDS-defining cancer and 272 of AIDS-defining cancer occurred among HIV-positive persons with a median age of 36 years (interquartile range, 29 to 43 years). With immediate ART, the 10-year risk for non-AIDS-defining cancer was 2.97% (95% CI, 2.37% to 3.50%) and that for AIDS-defining cancer was 2.50% (CI, 2.37% to 3.38%). Compared with immediate ART initiation, the 10-year absolute risk differences when deferring ART to CD4 counts less than 500 × 109 cells/L and less than 350 × 109 cells/L were 0.12 percentage point (CI, -0.01 to 0.26 percentage point) and 0.29 percentage point (CI, -0.03 to 0.73 percentage point), respectively, for non-AIDS-defining cancer and 0.32 percentage point (CI, 0.21 to 0.44 percentage point) and 1.00 percentage point (CI, 0.67 to 1.44 percentage points), respectively, for AIDS-defining cancer. LIMITATION Potential residual confounding due to observational study design. CONCLUSION In this young cohort, effects of immediate ART on 10-year risk for cancer were small, and further supportive data are needed for non-AIDS-defining cancer. PRIMARY FUNDING SOURCE Highly Active Antiretroviral Therapy Oversight Committee.