Neuronal Apoptosis in HIV-1-Associated Central Nervous Diseases and Neuropathic Pain

Abstract

The human immunodeficiency virus type 1 (HIV-1) pandemic has claimed over 20 million lives, with 38.6 million people worldwide currently infected (2009 AIDS Epidemic Update by UNAIDS/WHO, www.unaids.org), and will continue to contribute to human morbidity and mortality. The number of people living with HIV-1 continues to rise worldwide because of high rates of new infections and the success of antiretroviral therapy (ART, also known as the highly active antiretroviral therapy or HAART). HIV-1 infection results in a variety of syndromes involving both the central and peripheral nervous systems. HIV-1 invades the central nervous system (CNS) early during the course of infection and persists thereafter in the absence of treatment. HIV-1 infection of the CNS is often associated with neurological complications including HIV-1-associated severe and mild neurologic disorders. Prior to HAART, neurologic disorders were the first manifestation of symptomatic HIV-1 infection, affecting roughly 10% – 20% of patients and up to 60% of patients in the advanced stages of acquired immunodeficiency syndrome (AIDS)1. HIV-1 infection is also associated with neuropathic pain, which is caused by peripheral nervous system injury. The vast majority (up to 90%) of individuals infected with HIV-1 have pain syndromes that significantly impact their well-being2-13. A variety of pain syndromes including peripheral neuropathies, headache, oral and pharyngeal pain, abdominal and chest pain, arthralgias and myalgias as well as pain related to HIV-1/AIDS-associated malignancies such as Kaposi’s sarcoma14,15. Pain occurs at all stages of HIV-1 infection, although its severity and frequency are correlated with disease progression2,16. In the era of HAART, patients infected with HIV-1 live longer, and management of their symptoms including pain has emerged as a top priority for HIV-1 clinical and translational research.