Risk for non–AIDS-defining and AIDS-defining cancer of early versus delayed initiation of antiretroviral therapy. Annals of Internal Medicine
Chammartin et al. aimed to assess the impact of deferred and immediate start of antiretroviral therapy (ART) on the development of non-AIDS and AIDS-defining cancer.
Authors estimated the occurrence of cancer among participants from the D:A:D study and used causal inference methods to emulate a pragmatic trial comparing 3 treatment strategies: Immediate treatment irrespective of CD4 cell count, and treatment start at a CD4 cell count of less than 500 cells/µL or less than 350 cells/µL.
The study population included 8’318 individuals with a median age of 36 years (IQR 29–43), 77% were men, and the median CD4 cell count at baseline was 410 cells/µL (IQR 260–583). Over a median follow-up of 8.3 years, 231 persons developed non-AIDS defining (mainly Hodgkin lymphoma, lung, anal and prostate cancer) and 272 developed AIDS-defining cancer (Non-Hodgkin lymphoma, Kaposi sarcoma and cervical cancer). With immediate ART, the 10-year risk for AIDS-defining cancer was 2.50%, compared to 2.80% when treatment was started with a CD4 cell count below 500 cells/µL (difference to immediate treatment 0.32 percentage points, 95% CI 0.21–0.44), and 3.51% with a CD4 cell count below 350 cells/µL (difference 1.00 percentage points, CI 0.67–1.44). Differences in risk between the three strategies for the development of non-AIDS defining cancers were not statistically significant.
Taken together, this study shows that compared to a delayed ART start, immediate therapy leads to lower rates of AIDS-defining cancers. However, the risk reduction with immediate therapy is small and remains inconclusive for non-AIDS defining cancer. This is reassuring since almost half of patients currently start ART with a CD4 cell count below 500 cells/µL due to delayed diagnosis. Future research will need to better characterize the mechanisms behind the increased risk of cancer among people living with HIV compared with the general population.