Immediate antiretroviral therapy reduces risk of infection-related cancer during early HIV infection. Clinical Infectious Disease
The Strategic Timing of Antiretroviral Treatment (START) trial randomized HIV-infected adults with a CD4 count >500 cells/μL to immediate combination antiretroviral therapy (cART) initiation or cART deferral until CD4 counts dropped below 350 cells/μL. In the START trial, immediate cART reduced risk of cancer by 64%. In the current study, Borges et al. aimed at determine factors associated with cancer development among START participants and to assess mediators of the benefit of immediate cART in reducing cancer risk. Of note, infection-related cancer was defined as cancer driven by the following infectious agents: human herpesvirus 8 (Kaposi sarcoma), Epstein-Barr virus (non-Hodgkin lymphoma, Hodgkin lymphoma), and human papillomavirus (anal cancer, cervical cancer). All other malignancies were classified as infection-unrelated cancer.
There were 14 malignancies among persons randomized to the immediate cART arm (6 infection-related and 8 infection-unrelated) and 39 malignancies in the deferred arm (23 infection-related and 16 infection-unrelated). Immediate cART significantly reduced the risk of infection-related cancer by 74% (hazard ratio [HR] of immediate vs deferred cART initiation, 0.26), and the risk of infection-unrelated cancer by 51% (HR, 0.49). There was no statistical significance for infection-related vs infection-unrelated cancers. Independent baseline predictors of infection-related cancer were older age (HR, 1.42), higher BMI (HR, 1.47), low- to middle-income region (HR, 3.40), baseline HIV RNA (HR, 2.01) and baseline CD8 count (HR, 1.13). Older age (HR, 2.54) and baseline CD8 count (HR, 1.12) were the only independent predictors of infection-unrelated cancer. Adjustment for latest HIV RNA level, but not for CD4 cell count or cancer risk factors, attenuated the effect of immediate cART on infection-unrelated cancer.
In sum, immediate cART initiation significantly reduced the risk of cancer. With regard to infection-related cancer, this effect was mainly driven by a reduction in cases of Kaposi sarcoma and non-Hodgkin lymphoma. Adjustment for latest HIV RNA level suggest that the benefit of immediate cART does not be solely attributable to HIV RNA suppression and may also be mediated by other mechanisms.