• Frédérique Chammartin, Sara Lodi, Roger Logan, Lene Ryom, Amanda Mocroft, Ole Kirk, d'Arminio MonforteAntonellaA0000-0003-0073-1789Azienda Ospedaliera-Polo, Universitario San Paolo, Milan, Italy (A.D.M.)., Peter Reiss, Andrew Phillips, Wafaa El-Sadr, Camilla I Hatleberg, Christian Pradier, Fabrice Bonnet, Matthew Law, Stéphane De Wit, Caroline Sabin, Jens D Lundgren, Heiner C Bucher, and D:A:D Study Group.
• University Hospital Basel and University of Basel, Basel, Switzerland (F.C., H.C.B.).
• Ann. Intern. Med. 2021 Jun 1; 174 (6): 768-776.

BackgroundImmediate 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.ObjectiveTo estimate the long-term risk difference for cancer with the immediate ART strategy.DesignMultinational prospective cohort study.SettingThe 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.Participants8318 HIV-positive persons with at least 1 measurement each of CD4 cell count and viral load while ART-naive (study period, 2006 to 2016).MeasurementsThe 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.ResultsDuring 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.LimitationPotential residual confounding due to observational study design.ConclusionIn 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 SourceHighly Active Antiretroviral Therapy Oversight Committee.

19 keywords...

hide…