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SHOULD WE BE TESTING FOR BASELINE INTEGRASE RESISTANCE?
Yiannis Koullias1, Paul E. Sax1, Rochelle P. Walensky2, Emily P. Hyle2
1Brigham and Women's Hosp, Boston, MA, USA,3Massachusetts General Hosp, Boston, MA, USA
Treatment guidelines recommend baseline genotype resistance testing in new HIV diagnoses to guide selection of 1st-line therapy. While integrase strand transfer inhibitors (INSTIs) are recommended for initial treatment, most genotype tests do not assess INSTI resistance (INSTI-R). Given the low rate of transmitted INSTI-R, it is unclear if baseline testing would provide value. We examine the conditions under which INSTI-R testing might be cost-effective.
We use a decision tree to examine the incremental cost-effectiveness ratio (ICER) of INSTI-R testing vs. no testing. Results are based on differences in 96-wk quality-adjusted life expectancy (QALE), assuming equivalent outcomes thereafter. In the base case, the prevalence of transmitted INSTI-R is 0.1%, derived from published studies. Those who undergo INSTI-R testing and have resistance detected at baseline start a DRV/r-based regimen. The FLAMINGO trial provides estimates of 96-wk HIV RNA suppression rates with DTG (80.1%) and DRV/r (67.8%)-based regimens. For those with INSTI-R but without an INSTI-R test, we presume a 30% probability of success on DTG, since many INSTI-R isolates remain susceptible to DTG. In the base case, we presume a quality of life (QoL) reduction for those experiencing virologic failure (~3%). Costs include: INSTI-R $250/test; DTG-based ART ($38,150/yr) and DRV/r-based ART ($44,400/yr). In sensitivity analyses, we examine how changes in these parameters influence the conclusions.
Compared to a no test strategy, the INSTI-R test decreased QALE by 1.23x10^-6 QALY and increased per person costs by $250 at 96-wk; hence, not performing the test was the preferred strategy. Reducing QoL for DRV/r treatment further strengthened the preference for no test, even at implausibly high levels of transmitted INSTI-R. In sensitivity analyses, reducing DTG suppression with undiagnosed INSTI-R to <20% and increasing PI-regimen efficacy to >80% yielded improved clinical outcomes, but the ICER of INSTI-R testing was not cost effective, well exceeding $1 million/QALY. Base-case results were similar when an NNRTI was substituted for DRV/r.
At an estimated INSTI-R prevalence of 0.1% and a current INSTI-R test cost of $250, baseline INSTI-R testing results in worse clinical outcomes and higher costs than no test. A no test strategy remains preferred if there is a possibility of INSTI-suppression despite detected INSTI-R, or if there is a QoL benefit to PI avoidance, regardless of the prevalence of INSTI-R.