Individualized Antiretroviral Initiation Rules

Abstract

In this chapter, TMLE is illustrated with a data analysis from a longitudinal observational study to investigate “when to start” antiretroviral therapy to reduce the incidence of AIDS-defining cancer (ADC), defined as Kaposi sarcoma, non-Hodgkin’s lymphoma, or invasive cervical cancer, in a population of HIV-infected patients. A key clinical question regarding the management of HIV/AIDS is when to start combination antiretroviral therapy (ART), defined in the Department of Health and Human Services (2004) guidelines as a regimen containing three or more individual antiretroviral medications. CD4+ T-cell count levels have been the primary marker used to determine treatment eligibility, although other factors have also been considered, such as HIV RNA levels, history of an AIDS-defining illness (Centers for Disease Control and Prevention 1992), and ability of the patient to adhere to therapy. The primary outcomes considered in ART treatment guidelines described above have always been reductions in HIV-related morbidity and mortality. Until recently, however, guidelines have not considered the effect of CD4 thresholds on the risk of specific comorbidities, such as ADC. In this analysis, we therefore evaluate how different CD4-based ART initiation strategies influence the burden of ADC. We are analyzing ADC here since it is well established that these malignancies are closely linked to immunodeficiency.