GENOTYPIC TESTING

CLINICAL RATIONALE

Drug-resistance testing is recommended at entry into HIV care to identify the presence of transmitted drug-resistant mutations in relevant viral genes. Untreated HIV replicates rapidly, and during the viral replication process there is a high mutation rate supporting the indication of initial resistance testing. Resistance tests are most reliable when the HIV RNA level is above1000 copies/mL, such as when a patient is treatment-naïve.

The NYSDOH, DHHS, IAS-USA and WHO clinical guidelines recommend resistance testing with rapid initiation of ART. Most importantly, these experts agree that treatment initiation should not be delayed pending resistance test results. Once the results are reported, the initial regimen can be modified if necessary.

Genotype tests are preferred over phenotype tests in treatment-naïve patients because genotype tests are more likely to detect mutations that occur during reversion to wild-type virus. In addition, genotype tests have lower costs, results are available within 1-2 weeks and laboratory reports are generally easy to interpret. 1

REMEMBER

  • Include PR, INSTI and RT genotype testing with initial bloodwork
  • Genotype testing informs potential modifications to initial regimen
  • Baseline testing in this population is cost effective [1]
  • Do not delay treatment initiation pending results

TESTS TO ORDER

Standard genotypic drug-resistance testing in treatment-naïve persons involves testing for mutations in the reverse transcriptase (RT), integrase strand transfer inhibitor (INSTI), and protease (PR) genes. The prevalence of integrase strand transfer inhibitor (INSTI) resistance remains low compared with RT and PR resistance. However, INSTI resistance may become a concern due to the increased use of integrase-based treatment regimens. [2], [3]

For any questions regarding resistance tests or results, HIV experts are available through the Clinical Education Initiative line at 866-637-2342.

Bibliography

1. Sax PE, Islam R, Walensky RP, et al. Should resistance testing be performed for treatment-naive HIV-infected patients? A cost-effectiveness analysis. Clin Infect Dis. 2005;41(9):1316-1323. Available at: https://www.ncbi.nlm.nih.gov/pubmed/16206108.
2. Doyle T, Dunn DT, Ceccherini-Silberstein F, et al. Integrase inhibitor (INI) genotypic resistance in treatment-naive and raltegravir-experienced patients infected with diverse HIV-1 clades. J Antimicrob Chemother. 2015;70(11):3080-3086. Available at: http://www.ncbi.nlm.nih.gov/pubmed/26311843.
3. Menza TW, Billock R, Samoff E, Eron JJ, Dennis AM. Pretreatment integrase strand transfer inhibitor resistance in North Carolina from 2010–2016. AIDS. 2017;31(16):2235-2244. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28991024