Human Immunodeficiency Virus 1 Drug Resistance by Next Generation Sequencing

This assay predicts HIV-1 resistance to protease inhibitors, nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, and integrase inhibitors. The protease gene, integrase gene, and the reverse transcriptase gene of the viral genome are sequenced using next generation sequencing. Drug resistance is assigned using the Stanford hivdb database.

This test should be used in conjunction with clinical presentation and other laboratory markers. A patient's response to therapy depends on multiple factors, including patient adherence, percentage of resistant virus population, dosing, and drug pharmacology issues.

This test detects populations down to 10 percent of the total population which may account for resistance interpretation differences between methods. Some insertions or deletions may be difficult to detect using this software.

Drug Resistance Interpretations are defined as follows:
-Not Determined indicates incomplete sequence coverage across a given gene or genes.
-Susceptible indicates no drug resistance mutations (DRMs) were detected.
-Potential Low-Level Resistance indicates the presence of DRMs that suggest prior antiretroviral (ARV) exposure or are associated with resistance only when they occur alongside other DRMs.
-Low-Level Resistance indicates the presence of DRMs that are associated with reduced in vitro ARV susceptibility or a suboptimal virological response to ARV treatment.
-Intermediate Resistance indicates that while there is a high likelihood of reduced ARV activity due to the virus's DRMs, the ARV is still expected to retain significant antiviral activity.
-High-Level Resistance indicates the presence of DRMs predicted to confer a level of resistance similar to that seen in viruses with the highest levels of reduced in vitro susceptibility or those with little to no virological response to ARV treatment.

Mutations are classified as follows:
-Drug Resistance Mutations reduce susceptibility of specific drug classes whether found in isolation or in combination with other drugs.
-Accessory Mutations reduce susceptibility of specific drug classes only when found in combination with drug resistance mutations.
-Additional mutations have cleared or approved by the US Food and Drug Administration associated with drug resistance.
-Uncalled mutation sites are known locations of drug resistance mutations that have an inadequate number of sequencing reads to accurately determine if mutations are present.