Testing for integrase inhibitor resistance among patients who were newly diagnosed with HIV produced poorer clinical outcomes and raised treatment costs, according to recently published findings.
“The Panel on Antiretroviral Guidelines for Adults and Adolescents of the Department of Health and Human Services, the European AIDS Clinical Society and the International AIDS Society-USA panel recommend genotype drug resistance testing for people newly diagnosed with HIV prior to ART initiation,” Emily P. Hyle, MD, MSc, of the division of infectious diseases at Massachusetts General Hospital, Boston, and colleagues wrote. “The goal of this testing is to avoid the selection of therapies to which the patient is already resistant, thereby improving treatment outcomes. Given the low prevalence of transmitted [integrase inhibitor] resistance and the susceptibility of some [integrase inhibitor-resistant] virus to [dolutegravir-based] regimens, it is not clear if [integrase inhibitor resistance] testing before ART initiation provides additional value over standard genotypes.”
The researchers evaluated clinical outcomes, costs and cost-effectiveness of adding integrase inhibitor resistance to the initial evaluation of newly diagnosed patients with HIV using a decision tree model that simulated an ART-naive patient undergoing standard baseline lab work. Hyle and colleagues compared standard genotype testing plus integrase inhibitor resistance testing with standard genotype testing without testing for integrase inhibitor resistance, analyzing patient outcomes at 96 weeks.
The model had all patients who did not undergo resistance testing begin dolutegravir-based treatment after genotype testing, and assumed 12-week suppression rates of 90% for integrase inhibitor-susceptible virus vs. 35% for integrase inhibitor-susceptible virus. Patients not suppressed at 12 weeks underwent resistance testing and were switched to darunavir treatment in the event of integrase inhibitor resistance. For those who did undergo resistance testing, patients were diagnosed as resistant or susceptible before starting ART. The costs included ART ($41,100-$44,900 per year) and integrase inhibitor resistance tests ($175). Resistance prevalence was estimated at 0.1%.
Regardless of the prevalence of resistance transmission, patients who underwent resistance testing showed worse clinical outcomes and faced additional costs of $200 per person each year, the researchers reported. Not testing was the preferred method unless suppression of integrase inhibitor-resistant virus was less than 20% with dolutegravir, or suppression with darunavir was greater than 92%. Hyle and colleagues reported that univariate analysis showed integrase inhibitor testing was never cost-effective, even when researchers estimated testing at $5 or “under the rare circumstances when [integrase inhibitor resistance testing] resulted in better clinical outcomes.” The same held true in multivariate analyses, according to the researchers.
“In summary, testing for baseline [integrase inhibitor resistance] prior to ART initiation resulted in worse clinical outcomes and cost more than no [integrase inhibitor resistance] testing, as [dolutegravir]-based therapy may succeed despite transmitted [integrase inhibitor resistance]. Furthermore, even if virologic failure occurred, the duration of this viremia would be limited given routine viral load monitoring, and patients could be switched rapidly to an alternative suppressive regimen,” the researchers wrote. “Based on these results, an assessment for transmitted [integrase inhibitor resistance] at the time of HIV diagnosis should not be recommended in treatment guidelines.” – by Andy Polhamus
Disclosure: Hyle reports no relevant financial disclosures. Please see the full study for a complete list of all other researchers’ relevant financial disclosures.