Mini review: Promotion of substance abuse in HIV patients: Biological mediation by HIV-1 Tat protein

Neurosci Lett. 2021 May 14;753:135877. doi: 10.1016/j.neulet.2021.135877. Epub 2021 Apr 7.


Despite successful viral suppression by combinatorial anti-retroviral therapy, HIV infection continues to negatively impact the quality of life of patients by promoting neuropathy and HIV-Associated Neurocognitive Disorders (HAND), where substance use disorder (SUD) is highly comorbid and known to worsen health outcomes. While substance abuse exacerbates the progression of HIV, emerging evidence also suggests the virus may potentiate the rewarding effect of abused substances. As HIV does not infect neurons, these effects are theorized to be mediated by viral proteins. Key among these proteins are HIV-1 Tat, which can continue to be produced under viral suppression in patients. This review will recap the behavioral evidence for HIV-1 Tat mediation of a potentiation of cocaine, opioid and alcohol reward, and explore the neurochemical dysfunction associated by Tat as potential mechanisms underlying changes in reward. Targeting rampant oxidative stress, inflammation and excitotoxicity associated with HIV and Tat protein exposure may prove useful in combating persistent substance abuse comorbid with HIV in the clinic.

Keywords: Behavior; HIV; Neurochemistry; Reward; Substance use disorder; Tat protein.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Analgesics, Opioid / adverse effects
  • Analgesics, Opioid / pharmacokinetics
  • Animals
  • Brain / metabolism
  • Brain / physiopathology
  • Cocaine / adverse effects
  • Cocaine / pharmacokinetics
  • Disease Models, Animal
  • Ethanol / adverse effects
  • Ethanol / pharmacokinetics
  • HIV Infections / complications*
  • HIV Infections / psychology
  • HIV Infections / virology
  • HIV-1 / metabolism*
  • Humans
  • Mice
  • Quality of Life
  • Reward*
  • Substance-Related Disorders / physiopathology*
  • Substance-Related Disorders / psychology
  • Substance-Related Disorders / virology
  • tat Gene Products, Human Immunodeficiency Virus / metabolism*


  • Analgesics, Opioid
  • tat Gene Products, Human Immunodeficiency Virus
  • Ethanol
  • Cocaine