The effects of cocaine on HIV transcription

Abstract

Illicit drug users are a high risk population for infection with the Human Immunodeficiency Virus (HIV). A strong correlation exists between prohibited drugs use and an increase rate of HIV transmission. Cocaine stands out as one of the most frequently abused illicit drugs and its use is correlated with HIV infection and disease progression. The central nervous system (CNS) is a common target for both drugs of abuse and HIV, and cocaine intake further accelerates neuronal injury in HIV patients. Although the high incidence of HIV infection in illicit drug abusers is primarily due to high risk activities such as needle sharing and unprotected sex, several studies have demonstrated that cocaine enhances the rate of HIV gene expression and replication by activating various signal transduction pathways and downstream transcription factors. In order to generate mature HIV genomic transcript, HIV gene expression has to pass through both the initiation and elongation phases of transcription, which requires discrete transcription factors. In this review, we will provide a detailed analysis of the molecular mechanisms that regulate HIV transcription and discuss how cocaine modulates those mechanisms to upregulate HIV transcription and eventually HIV replication.

Prevalence and Associations of Illicit Drug and Polydrug Use in People Living with HIV in Vienna

“…Active drug use was found to be associated with adherence problems in other studies as well where non-adherence was also found to be more prevalent in polydrug users, which in our study carried an 8 times higher risk for polydrug use in the multivariant model 19 , 27 , 45 – 47 . Reasons for this may be due to the disruptive influence of illicit drugs on the daily rhythm or due to neural damage that leads into cognitive problems as some illicit drugs cause neural damage and contribute to higher viral replication that causes additional tissue damage 23 – 25 , 46 . In terms of ART a particularly high adherence level of over 85% is necessary to achieve viral RNA suppression in patients receiving ART 20 .…”

“…Furthermore, illicit drug use has been found to be a factor of non-adherence by causing temporary cognitive impairment or by drug-drug interaction causing potentially toxic side effects, on the other hand also limiting the effectiveness due to shared metabolic pathways 21 , 22 . Illicit drug use, especially cocaine, amphetamines, methamphetamines, heroin and morphine have been also known to increase the HIV replication and cause epigenetic changes in brain tissue, which can further have a synergistic effect and accelerates neural injury and cognitive impairment 23 – 25 .…”

Community-acquired lower respiratory tract infections in HIV-infected patients on antiretroviral therapy: predictors in a contemporary cohort study

“…A previous study has shown that smoking illicit drugs (marijuana, cocaine, or crack) increased the risk of CAP in HIV positive individuals [26]; in multivariate analysis smoking illicit drugs (OR 2.24, 95% CI 1.03–4.89) remained significantly associated with bacterial pneumonia. More recently, it has been demonstrated that cocaine enhances the rate of HIV gene expression and replication by activating various signal transduction pathways and downstream transcription factors [27], and epidemiological associations between cocaine use and progression to AIDS [28] may have this pathophysiological underlying role. However, it must be emphasized that abusing drugs is well known to lead to poor compliance with antiretroviral therapy.…”

Cocaine evokes a profile of oxidative stress and impacts innate antiviral response pathways in astrocytes

“…Cocaine use disorder (CUD) continues to be a significant public health problem, with rising cocaine- related overdose deaths associated with the opioid epidemic (McCall Jones et al, 2017). Cocaine is a powerful psychostimulant that acts within the central nervous system (CNS) to evoke addictive properties (for reviews) (Cunningham and Anastasio, 2014; Koob and Volkow, 2016) and its actions in the CNS contributes to the neuropathological signature of human immunodeficiency virus (HIV)-1 and the transmission and progression of acquired immunodeficiency syndrome (AIDS) (for review) (Tyagi et al, 2016). Cocaine also increases the severity of viral-mediated neurotoxicity (Fiala et al, 2005; Yao et al, 2009) which culminates in higher viral loads, neurotransmitter dysregulation, oxidative stress and neuroinflammation (Ersche et al, 2013; Swepson et al, 2016; Yao et al, 2009).…”