Background: For people newly diagnosed with HIV, US guidelines recommend standard genotype testing to detect transmitted resistance to NNRTI, NRTI, and PIs, but not INSTIs. With INSTI-based regimens as preferred first-line therapy, results of a standard genotype at HIV diagnosis will influence only second-line ART selection for people who experience an adverse event (AE) on INSTIs and require an ART switch.
Methods: We used the Cost-effectiveness of Preventing AIDS Complications (CEPAC) model to examine the value of standard genotype at HIV diagnosis for people starting dolutegravir, comparing: 1) No Genotype and 2) Genotype. In both strategies (Table), patients with an AE to dolutegravir switch to rilpivirine, except those with known NNRTI-resistance in Genotype who instead transition to darunavir. In No Genotype, patients with undiagnosed NNRTI-resistance have lower viral suppression with second-line rilpivirine. In both strategies, patients with virologic failure then have genotypes to guide subsequent ART. Standard genotype costs $350; ART costs $3000-3700/month. In sensitivity analysis, we varied the prevalence of transmitted NNRTI-resistance (base case, 8%), prevalence of AEs on dolutegravir (base case, 14%), and suppression of NNRTI-resistant virus with rilpivirine. Model outcomes (discounted 3%/year) included quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). We considered ICERs< $100,000/QALY cost-effective.

 No GenotypeGenotype
1st-line ARTDolutegravirDolutegravir
48-week suppression93%93%
Monthly cost$3,700$3,700
2nd-line ARTRilpivirineRilpivirineRilpivirineDarunavir
48-week suppression83%37%83%83%
Monthly cost$3,000$3,000$3,000$3,700
[Table. Strategy-specific response to adverse events on first-line dolutegravir.]

Results: Among all newly-diagnosed patients, No Genotype resulted in 15.3043 QALYs and cost $730,240/person; Genotype gained 0.0003 QALYs and cost $850/person more (ICER, $2.8 million/QALY gained). Among patients with transmitted NNRTI-resistance, Genotype resulted in 0.0039 additional QALYs compared to No Genotype and cost $6,590/person more (ICER, $1.6 million/QALY gained). At base case assumptions, 1.1% of newly diagnosed people with HIV would benefit clinically from Genotype, but it would cost $114,510 to test 100 patients for a maximum gain of 2.6 quality-adjusted days for one person. Genotype was not cost-effective compared to No Genotype unless prevalence of transmitted NNRTI-resistance >40% and AEs on dolutegravir >40%, with no suppression of NNRTI-resistant virus on rilpivirine-based ART (Figure).
Conclusions: With INSTI-based regimens as first-line treatment in the US, the standard genotype test at HIV diagnosis offers minimal clinical benefit, is more expensive, and is not cost-effective. Practice guidelines should consider removing genotypes from the recommended baseline evaluation.