Clinical Background

For people with HIV, combination antiretroviral therapy (cART) can reduce viral replication, reduce HIV transmission, and improve clinical outcomes.1,2  However, incomplete viral suppression can lead to drug-resistant virus and therapeutic failure.3–5 Genotypic resistance testing is recommended for selection of antiretroviral regimens before initiating cART, to assess for transmitted resistant virus, and at the time of treatment failure.1,2 

Standard genotypic resistance tests measure viral RNA in plasma and are appropriate for viremic individuals. However, standard tests may not be appropriate for individuals with viral suppression, as viral levels may be too low for accurate genotyping. Individuals with viral suppression may be candidates for a regimen switch due to drug toxicity, regimen simplification, or other reasons. When considering a regimen switch, guidelines recommend reviewing an individual's cART history and prior resistance testing results.1,2

When viral RNA levels are low and cART treatment history and prior resistance testing results are unavailable, proviral DNA genotypic testing may be useful.1,2 Proviral DNA is viral DNA that is integrated into the host genome; thus, it can be assessed when plasma RNA levels are low or undetectable. It also represents an archive of viral mutations that can differ from plasma RNA.

Although the clinical utility of proviral DNA genotypic testing has not yet been established, resistance mutations present in plasma viral RNA prior to virologic suppression can often be identified in proviral DNA. For virally suppressed individuals, proviral DNA genotypic testing is 75% to 89% concordant with plasma viral RNA testing for protease and reverse transcriptase mutations.6–8  In addition, proviral DNA testing may detect resistance mutations that may be archived and, thus, not detected in plasma viral RNA.6–9 

As part of the HIV-1 Resistance, Proviral DNA (RTI, PI, Integrase Inhibitors) test (test code 94807), Quest Diagnostics offers HIV-1 proviral DNA testing for multiple cART classes, including nucleoside and non-nucleoside reverse transcriptase inhibitors (RTIs), protease inhibitors (PIs), and integrase inhibitors. RTI and PI testing and Integrase Inhibitor testing are separately available:

• HIV-1 Resistance, Proviral DNA (RTI, PI Inhibitors): test code 94808
• HIV-1 Resistance, Proviral DNA (Integrase Inhibitors): test code 94809

In addition, Quest offers HIV-1 Resistance and Coreceptor Tropism, Proviral DNA (test code 94810), which includes RTI, PI, integrase inhibitors, and tropism. This panel also provides tropism testing that may be considered for screening virologically suppressed patients prior to prescribing a CCR5 antagonist.