Neurological disease: the effects of HIV and antiretroviral therapy and the implications for early antiretroviral therapy initiation

Abstract

Purpose of review: The purpose of this review is to examine the literature regarding HIV-associated neurocognitive disorders, early HIV infection of the central nervous system (CNS), the role of the peripheral immune system in controlling HIV infection and disease within the brain and the potential role that early antiretroviral treatment may play in the preservation of neurocognitive health in patients with more than 500 CD4+ cells/microl.

Recent findings: In the post highly active antiretroviral therapy (HAART) era, HIV-associated neurocognitive disorders remain prevalent and even mild-moderate immunosuppression carries a risk for the development of HIV-associated dementia. HIV infection of the CNS occurs early in the illness, and data suggest that a robust peripheral immune system is key to the long-term control of CNS HIV infection. HAART results in clinical, neuropsychological and neuroradiological improvement in patients with HIV-associated neurocognitive disorders, and the prescription of HAART regimens with good cerebrospinal fluid penetration appears to be preferable in this setting. There is little evidence that HAART causes CNS toxicity. The benefits and risks of HAART in the preservation or enhancement of neurocognitive function in well, HIV-infected patients with more than 500 CD4+ cells/microl are unknown.

Summary: The prescription of HAART in well, HIV-infected patients with high CD4+ cell counts may afford enhanced control of CNS HIV infection as a result of the benefits of HAART upon peripheral immune function. In turn, this may result in superior or preserved neurocognitive performance in comparison to the current practice of commencing HAART when CD4+ cells reach 350 cells/microl or lower. This hypothesis will be tested in an upcoming randomized clinical trial.