Despite the development of powerful antiretroviral drugs, HIV-1 associated neurological disorders (HAND) will affect approximately half of those infected with HIV-1. Combined anti-retroviral therapy (cART) targets viral replication and increases T-cell counts, but it does not always control macrophage polarization, brain infection or inflammation. Moreover, it remains difficult to identify those at risk for HAND. New therapies that focus on modulating host immune response by making use of biological pathways could prove to be more effective than cART for the treatment of neuroAIDS. Additionally, while numerous HAND biomarkers have been suggested, they are of little use without methods for appropriate data integration and a systems-level interpretation. Machine learning, could be used to develop multifactorial computational models that provide clinicians and researchers with the ability to identify which factors (in what combination and relative importance) are considered important to outcome.