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Related Concept Videos

Retrovirus Life Cycles01:10

Retrovirus Life Cycles

Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the retrovirus to...
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Drug Toxicity: Dose-Dependent Reactions

Drug toxicities can be stratified into pharmacological, pathological, or genotoxic based on their mechanisms. The incidence and severity of these toxicities generally increase with the drug's concentration in the body and exposure time.Pharmacological toxicity is evident when the therapeutic effects of drugs overshoot into adverse reactions in a predictable, dose-dependent manner. Central nervous system (CNS) depression from barbiturates is a classic example, with effects escalating from...
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Drug toxicity quantifies the harm a compound causes to an organism, varying by dose and potentially impacting whole systems or specific organs like the liver. Toxic reactions may arise from venomous insect or spider bites, with effects ranging from mild symptoms to severe outcomes such as brain damage or death. Common forms of acute poisoning include ethanol intoxication and overdose of pain or fever medications, with substances like GHB and heroin being particularly lethal at doses close to...
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Adverse Drug Reactions (ADRs) are potential complications that arise during pharmacotherapy, influenced by multiple risk factors. Age plays a significant role; both neonates and the elderly are at heightened risk due to their respective immature and diminished metabolic and elimination processes. Gender also impacts ADRs, with females experiencing a 1.5 to 1.7-fold greater risk than males, which may be linked to pharmacokinetic, pharmacodynamic, and hormonal differences. Notably, neonates, the...
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Related Experiment Video

Updated: May 20, 2026

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
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Antiretroviral neurotoxicity.

Kevin Robertson1, Jeff Liner, Rick B Meeker

  • 1Department of Neurology, University of North Carolina, Chapel Hill, NC 27599, USA.

Journal of Neurovirology
|July 20, 2012
PubMed
Summary

This study assessed the neurotoxicity of 15 antiretroviral drugs. While some drugs showed toxicity at high concentrations, most were safe at clinically relevant levels for HIV patients.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Infectious Diseases

Background:

  • Combination antiretroviral therapy (CART) effectively suppresses HIV but has poor central nervous system (CNS) penetration.
  • HIV-associated neurocognitive disorders (HAND) remain a concern, necessitating better CNS drug strategies.
  • Understanding antiretroviral neurotoxicity is crucial for balancing efficacy and safety.

Purpose of the Study:

  • To evaluate the direct neurotoxic effects of 15 antiretroviral compounds.
  • To establish a foundation for dosing and drug selection guidelines to minimize neurotoxicity.
  • To assess neurotoxicity at clinically relevant concentrations in cerebrospinal fluid (CSF).

Main Methods:

  • Assessed direct effects of 15 antiretroviral compounds on neurons.

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  • Utilized sensitive indices of neural damage to quantify toxicity.
  • Determined median toxic concentrations (ng/ml) for each compound.

    • Main Results:

    • A wide range of neurotoxicities was observed, with median toxic concentrations from 2 to 10,000 ng/ml.
    • Toxicity was generally modest at clinically relevant CSF concentrations.
    • Highest neurotoxicity associated with abacavir, efavarenz, etravirine, nevaripine, and atazanavir.
    • Lowest neurotoxicity observed with darunavir, emtracitabine, tenofovir, and maraviroc.
    • No additive neurotoxic effects were found with clinically used drug combinations.

    Conclusions:

    • Provides initial neurotoxicity data for 15 antiretroviral drugs.
    • Supports the development of treatment strategies to mitigate antiretroviral neurotoxicity.
    • Highlights the need to balance CNS drug penetration benefits against neurotoxicity risks.