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 1.23×10^-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.