Related Experiment Video
Updated: May 26, 2026
10:29
Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors
Published on: May 9, 2025
Metabolic Abnormalities Associated with the Use of Protease Inhibitors and Non-nucleoside Reverse Transcriptase
Madhu N Rao1, Grace A Lee, Carl Grunfeld
1Department of Medicine, University of California at San Francisco.
American Journal of Infectious Diseases
|December 14, 2011
Summary
Protease inhibitors and non-nucleoside reverse transcriptase inhibitors used for HIV/AIDS treatment can cause metabolic issues like insulin resistance and high triglycerides. Factors include drug effects, patient health, and genetics.
Area of Science:
- Metabolic disorders
- Pharmacology
- Virology
Background:
- Antiretroviral therapies, including protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs), are crucial for managing Human Immunodeficiency Virus (HIV) infection and Acquired Immunodeficiency Syndrome (AIDS).
- These medications can lead to significant metabolic derangements, impacting patient health and treatment adherence.
Purpose of the Study:
- To summarize the metabolic abnormalities associated with PI and NNRTI use in HIV/AIDS treatment.
- To identify specific metabolic disturbances, such as insulin resistance and dyslipidemia.
- To explore the contributing factors to these metabolic changes.
Main Methods:
- Review of existing literature on the metabolic effects of antiretroviral drugs.
- Analysis of reported cases linking specific drug classes to metabolic abnormalities.
- Identification of key metabolic parameters affected, including glucose and lipid profiles.
Main Results:
- HIV/AIDS treatments involving PIs and NNRTIs are linked to insulin resistance, elevated triglycerides, and increased low-density lipoprotein (LDL) cholesterol.
- Metabolic disturbances result from a multifactorial interplay of drug effects, improved patient health status, HIV disease progression, and individual genetic susceptibility.
- Indinavir is particularly associated with inducing insulin resistance, while ritonavir is linked to the most severe hypertriglyceridemia.
Conclusions:
- Metabolic abnormalities are a significant concern in patients receiving PI and NNRTI-based HIV/AIDS therapy.
- Understanding the contributing factors is essential for managing and mitigating these side effects.
- Drug-specific effects, such as those seen with indinavir and ritonavir, require careful consideration in patient management.
Related Concept Videos
01:27Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase
Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...
01:21Overview of Protein Metabolism
Proteins are broken down into amino acids during digestion. Unlike fats and carbohydrates, which are stored for later use, proteins are not. Instead, amino acids are either used to produce ATP through oxidation or contribute to the creation of new proteins for the growth and repair of the body. Any surplus amino acids from the diet are converted into glucose or triglycerides rather than excreted.
Amino acids play various roles in the body once they are absorbed into cells. They are restructured...
Amino acids play various roles in the body once they are absorbed into cells. They are restructured...
01:25Pharmacokinetics: Drug–Drug Interactions
Drug interactions occur when the pharmacological effect of one drug is altered by another substance, either enhancing or diminishing its activity. The drug whose activity is altered is known as the object drug, and the substance causing the alteration is called the agent drug or the precipitant. The net effects of these interactions are mostly undesirable, leading to decreased effectiveness or increased adverse effects. In rare cases, interactions can be beneficial, such as the enhanced...
01:25Bioactivation and Tissue Toxicity
Bioactivation is a metabolic process that transforms less reactive substances into highly reactive metabolites, initiating tissue toxicity. This transformation can lead to various toxic effects, including carcinogenesis and teratogenesis. Reactive metabolites are classified into two main types: electrophiles and free radicals.Electrophiles are electron-deficient species and are produced primarily by the enzyme cytochrome P-450 during the metabolism of compounds containing carbon, nitrogen, or...
01:26Pharmacokinetics: Drug–Food and Drug–Viral Interactions
A drug interaction occurs when the concurrent use of another drug, food, or an external substance alters the pharmacological activity of a drug. This interaction can modify the action of the original drug, affecting its effectiveness and safety.Drug–food interactions are significant as they impact drug absorption, metabolism, and excretion. For example, grapefruit juice is a well-known disruptor of drug metabolism. It inhibits the cytochrome P450 3A4 enzyme, crucial for the metabolism of many...
01:26Pharmacokinetics in Pediatric Patients: Drug Excretion
In pediatric medicine, understanding the renal function and drug elimination nuances is crucial for administering safe and effective treatments. Newborns, in particular, display markedly slower renal functions than adults, profoundly affecting how drugs are cleared from their bodies. This slower drug clearance requires clinicians to extend the dosing intervals for many medications to prevent drug accumulation and toxicity while ensuring therapeutic efficacy.One key area where these adjustments...