Acceleration of HIV dementia with methamphetamine and cocaine

Cocaine promotes both initiation and elongation phase of HIV-1 transcription by activating NF-κB and MSK1 and inducing selective epigenetic modifications at HIV-1 LTR

“…Despite the use of highly active antiretroviral therapy (HAART), the prevalence of HIV-associated neurocognitive disorder or HAND in drug abusing populations is significantly high (Ferris et al, 2008; Nath et al, 2002; Nath et al, 2001). HIV-1 can be found in the CNS within days of infection, where it can be present either in a transcriptionally active or impaired form (Kaul et al, 2001; Nath et al, 2002; Nath et al, 2001).…”

“…HIV-1 can be found in the CNS within days of infection, where it can be present either in a transcriptionally active or impaired form (Kaul et al, 2001; Nath et al, 2002; Nath et al, 2001). Within the brain, HIV-1 is harbored primarily in myeloid cells and these cell types act as the main HIV-1 reservoirs in the CNS (Nath et al, 2002; Nath et al, 2008).…”

“…In addition to increasing the severity of the infection (Arthur, 2008; Ioannidis et al, 2000; Skalka, 2013), cocaine impairs the normal function of the cells within the brain and promotes HIV-1 replication in the central nervous system (CNS) (Nath et al, 2002; Nath et al, 2001). The long-lived CNS glial cells, microglia, macrophages and astrocytes are the main targets and reservoirs of HIV-1 infection in the brain (Nath et al, 2002; Nath et al, 2008).…”

“…The long-lived CNS glial cells, microglia, macrophages and astrocytes are the main targets and reservoirs of HIV-1 infection in the brain (Nath et al, 2002; Nath et al, 2008). Previous studies reported that HIV-1 infected individuals who abuse cocaine experience a more severe and rapid onset of neuro-acquired immunodeficiency syndrome (neuroAIDS) than non-abusing individuals (Anthony et al, 1991; Chiasson et al, 1990; Ioannidis et al, 2000; Nath et al, 2001; Parikh et al, 2014). It has been well established that cocaine modulates several signaling pathways primarily MAPK pathway, PI3K/Akt pathway and PKC signaling pathways (Estaquier et al, 2013; Ioannidis et al, 2000; Liu et al, 2000; Nath et al, 2000a; Parikh et al, 2014; Skalka, 2013), which result in the activation of downstream protein factors, including transcription factors.…”

“…The NF-κB family consists of five related proteins, p65 (Rel A), Rel B, c-Rel, p50/p105 (NF-κB) and p52/p100 (NF-κB2) and they can form homo- or heterodimers with each other (Hayden and Ghosh, 2004). Of these, one of the best-characterized NF-κB heterodimers is comprised of Rel A (p65) and p50, which widely expressed and heavily involved in NF-KB-regulated transactivation (Nath et al, 2001; Schmitz and Baeuerle, 1991). In its inactive state, the NF-κB dimer is bound to the inhibitory IκB in the cellular cytoplasm (Hayden and Ghosh, 2004; Sobhian et al, 2010).…”