Related Experiment Video
Updated: Jul 4, 2026
08:46
Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
Published on: December 9, 2015
Consensus drug resistance mutations for epidemiological surveillance: basic principles and potential controversies
Robert W Shafer1, Soo-Yon Rhee, Diane E Bennett
1Division of Infectious Diseases, Stanford University, Stanford, CA, USA. rshafer@stanford.edu
Antiviral Therapy
|June 26, 2008
Summary
Monitoring transmitted HIV-1 drug resistance is crucial for effective treatment. This paper discusses defining key drug resistance mutations for accurate global surveillance and comparing resistance rates over time.
Area of Science:
- Virology
- Epidemiology
- Public Health
Background:
- HIV-1 drug resistance surveillance programs are essential for informing treatment guidelines and evaluating the success of HIV-1 treatment and prevention efforts.
- The World Health Organization (WHO) has initiated a global program for genotypic surveillance of HIV-1 drug resistance, emphasizing the need for a consensus definition.
- Accurate comparison of transmitted drug resistance rates across different regions and time periods necessitates a standardized definition of genotypic drug resistance.
Purpose of the Study:
- To review the data required for identifying sensitive and specific indicators of transmitted HIV-1 drug resistance among numerous mutations.
- To examine the methodology used in developing a prior list of drug resistance mutations for HIV-1 surveillance.
- To explore alternative approaches for defining genotypic drug resistance in the context of HIV-1 surveillance.
Main Methods:
- Review of existing data on HIV-1 drug resistance mutations.
- Analysis of criteria for sensitivity and specificity in identifying transmitted drug resistance indicators.
- Examination of the process for creating consensus definitions of genotypic drug resistance.
Main Results:
- Discussion on the challenges posed by HIV-1 diversity and the multitude of resistance mutations.
- Identification of critical data considerations for selecting reliable drug resistance mutation indicators.
- Review of a previously established method for HIV-1 surveillance mutation lists.
Conclusions:
- A consensus definition for genotypic drug resistance is vital for meaningful comparisons in global HIV-1 surveillance.
- Careful consideration of mutation data is necessary to establish sensitive and specific indicators of transmitted drug resistance.
- Ongoing evaluation and discussion of methodologies are important for refining HIV-1 drug resistance surveillance.
Related Concept Videos
02:56Treatment Resistant Cancers
Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
01:29Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
01:27Principles of Pharmacogenetics: Types of Genetic Variants
The human genome is over 99.9% identical between individuals, yet genetic differences exist at millions of bases. The human genome contains approximately 3 million variant positions per individual, many of which are heterozygous, contributing to genetic diversity and individual traits. Genetic variations include single-nucleotide polymorphisms (SNPs), insertions, deletions, and copy number variations (CNVs).SNPs, the most common variation, involve single-base changes in DNA. These can be...
01:25Clinical Significance of Antibiotic Resistance
Methicillin-resistant Staphylococcus aureus (MRSA) presents a critical public health threat, arising from its capacity to resist β-lactam antibiotics due to acquisition of the mecA gene within the staphylococcal cassette chromosome mec (SCCmec). This gene encodes penicillin-binding protein 2a (PBP2a), which impairs binding efficacy of methicillin and other β-lactams. MRSA has evolved into distinct clonal lineages impacting humans and animals alike, reinforcing its significance within the One...
01:19Pharmacovigilance
Post-marketing surveillance is a critical component of pharmaceutical regulation, often uncovering unanticipated adverse drug reactions (ADRs) once a drug is widely used over an extended period.
This process, termed pharmacovigilance, aims to detect, evaluate, and minimize harmful effects related to medication use. The data collection for pharmacovigilance depends on spontaneous reporting systems, where healthcare professionals or patients voluntarily report suspected ADRs.
In some cases, there...
This process, termed pharmacovigilance, aims to detect, evaluate, and minimize harmful effects related to medication use. The data collection for pharmacovigilance depends on spontaneous reporting systems, where healthcare professionals or patients voluntarily report suspected ADRs.
In some cases, there...
01:27Pharmacogenetics of Drug Metabolism: Overview
Genetic polymorphism in drug metabolism is crucial to the inter-individual variability observed in drug responses. Drug metabolism primarily involves the chemical modification of drugs and other xenobiotics to enhance their elimination by increasing their polarity. Two main classes of enzymes mediate this biotransformation process: Phase I enzymes, primarily cytochrome P450s, catalyze oxidation and reduction reactions, while other enzymes, such as esterases, mediate hydrolysis, and Phase II...