Human immunodeficiency virus (HIV) targets CD4+ lymphocytes, a critical component to proper functioning of the human immune system. HIV is a significant public health concern, having resulted in over 27 million deaths since its discovery. Currently, several different treatment options exist, with combination antiretroviral therapy (ART) at the forefront. Despite the success of ART therapy, there are number of problems, including poor patient compliance. Due to this, the appropriate time to initiate therapy in the treatment naïve patient is under continuous scrutiny. Recently, several trials have demonstrated evidence suggesting that initiating ART at high CD4+ counts in the treatment naïve patient is beneficial in preventing outcomes such as progression to AIDS and death due to complications from HIV. This review will discuss two trials influential in the recent change in The National Institute of Health's guidelines on therapy for treatment naïve patients. The trials reviewed here are the North Amencan AIDS Cohort Collaboration on Research Design (NA-ACCORD) and the Antiretroviral Therapy Cohort Collaboration (ART-CC). Despite the success of therapy, it is associated with many negative side effects and high cost which may affect patient compliance, lead to possible drug resistance and result in treatment failure. Along with the new evidence presented in clinical trials, these factors also must be considered when initiating therapy in the treatment naïve HIV patient.