Baseline Integrase Resistance at Time of HIV Diagnosis Results in Worse Clinical Outcomes, Higher Costs

Baseline testing for integrase strand transfer inhibitor (INSTI) resistance at the time of HIV diagnosis and prior to the start of antiretroviral therapy (ART) leads to worse clinical outcomes and costs more than not performing this testing, according to a decision analysis model developed by researchers at Brigham and Women’s Hospital and Massachusetts General Hospital in Boston (Clin Infect Dis 2017;65:1274-81).

Several advisory bodies recommend genotype resistance testing in newly diagnosed HIV patients prior to initiating ART, so that clinicians don’t start these individuals on therapies they’re already resistant to. INSTI-resistant virus among ART-naïve patients was first reported in 2011, but remains low. In addition, most INSTI-resistant cases have involved resistance to first- but not second-generation INSTIs. Most standard resistance genotype testing does not include INSTI resistance. Given these circumstances, the authors posited that INSTI resistance testing before commencing ART might not provide value over standard genotyping that tests for mutations in the reverse transcriptase and protease genes.

The decision analysis model compared 96-week clinical outcomes and cost-effectiveness in two strategies: one with INSTI resistance testing at HIV diagnosis, and one without. The model assumed a 0.1% base case prevalence of INSTI-resistant HIV. All patients who did not receive resistance testing would start on the second-generation INSTI, dolutegravir, after standard genotyping, resulting in a 90% 12-week viral suppression rate. Those not suppressed at this point would undergo resistance testing and repeat standard genotyping. If found to have INSTI-resistant HIV, they would change to ritonavir-boosted darunavir (DRV/r) ART.

In contrast, under the resistance testing strategy the model assumed that all patients would be diagnosed with either INSTI-resistant HIV or INSTI-sensitive HIV and would start either dolutegravir or DRV/r therapy. Resistance testing would cost $175 while ART would range from $41,100 to $44,900 per year.

When the authors compared INSTI resistance testing to no testing in ART-naïve patients who took either dolutegravir or DRV/r therapy, they found no resistance testing remained clinically preferred unless dolutegravir suppression of INSTI-resistant virus was <20% or 96-week DRV/r suppression was >92%. Upfront resistance testing also increased costs by $200 per patient per year.