NeuroHIV and use of addictive substances

In the past three decades, substance abuse has been identified as a key comorbidity of human immunodeficiency virus-1 (HIV-1) infection. Many studies have found that the use and abuse of addictive substances hastens the progression of HIV-1 infection and HIV-associated neurocognitive disorders. Advances in highly active antiretroviral therapy (HAART) in the mid-1990s have been successful in limiting the HIV-1 viral load and maintaining a relatively healthy immune response, allowing the life expectancy of patients infected with HIV to approach that of the general population. However, even with HAART, HIV-1 viral proteins are still expressed and eradication of the virus, particularly in the brain, the key reservoir organ, does not occur. In the post-HAART era, the clinical challenge in the treatment of HIV infection is inflammation of the central nervous system (CNS) and its subsequent neurological disorders. To date, various explicit and implicit connections have been identified between the neuronal circuitry involved in immune responses and brain regions affected by and implicated in substance abuse. This chapter discusses past and current medical uses of prototypical substances of abuse, including morphine, alcohol, cocaine, methamphetamine, marijuana, and nicotine, and the evidence that systemic infections, particularly HIV-1 infection, cause neurological dysfunction as a result of inflammation in the CNS, which can increase the risk of substance abuse.