It is estimated that almost 25% of untreated HIV-1 infected individuals and ~7% of HIV-1 infected patients treated with combined antiretroviral therapy (cART) develop HIV-associated dementia (HAD) [1
], a neurodegenerative syndrome that is clinically characterized by progressive cognitive, motor and behavioral abnormalities [5
]. HIV encephalitis (HIVE), the pathological correlate of HAD, is often accompanied by prominent microglial activation, formation of microglial nodules, perivascular accumulations of mononuclear cells, presence of multi-nucleated giant cells, and neuronal damage and loss [5
HIV-infection is often associated with the co-morbid condition of illicit drug abuse. Since most of these abused drugs, similar to HIV, also target the CNS, understanding the interplay of drugs of abuse and HIV-1 infection is of paramount importance. Both intravenous drug use (IVDU) and HIV infections are interlinked epidemics. About 33% of the newly reported drug users are IV injection users in the United States. It has been reported that HIV-1 infection is one of the major causes of mortality among Americans. Several earlier reports point to the use of cocaine as a risk for HIV-infection as well as it being independently linked with progression to AIDS [9
]. It is becoming increasingly clear that the number of HIV-infected patients that are also cocaine-abusers is constantly on a rise [12
]. Intriguingly, HIV-infected individuals with concomitant cocaine abuse also display increased severity and progression to NeuroAIDS. It can thus be envisioned that concurrent use of cocaine by HIV-infected individuals contributes to progression of clinically diagnosed AIDS.
cART usage has resulted in augmented longevity of HIV-infected individuals, however, there is a paradoxical accompaniment of increased prevalence of HAND (HIV-1-associated neurocognitive disorders) in these individuals. Symptoms of HAND range from the undetectable neurocognitive impairment to more severe form of encephalitis/dementia affecting about 8% of infected individuals. Similar to the therapy naïve individuals, even in the cART treated group, interaction of HIV with abuse of illicit drugs continues to remain problematic. Making matters worse is the inability of various cART regimens to penetrate the CNS, thus making the brain a viral sanctuary.
Brain is one of the major targets for cocaine. Cocaine has been shown to impair the functions of macrophages and lymphocytes [13
] and can also enhance the expression of HIV-1 in these cells [18
]. It has been postulated that cocaine could serve as a co-factor in the vulnerability and development of HAND [9
]. Epidemiological studies on drug abusers with NeuroAIDS associated abuse of cocaine (by any route of administration) to enhanced incidence of HIV seroprevalence and progression to AIDS [23
]. Both in vitro
and in vivo
studies have demonstrated the synergistic interactions of HIV-1 and cocaine abuse in the progression of HAND. This review aims to unravel interplay of cocaine and HIV-1 infection.