Hyle EP, Scott JA, Sax PE, et al. - In view of recommendation from US guidelines of performing genotype testing at human immunodeficiency virus (HIV) diagnosis (“baseline genotype”) to detect transmitted drug resistance (TDR) to nonnucleoside reverse transcriptase inhibitors (NNRTIs), nucleoside reverse transcriptase inhibitors (NRTIs), and protease inhibitors, researchers here sought to ascertain the impact of baseline genotypes on people initiating integrase strand inhibitor (INSTI)-based regimens which are now recommended as first-line antiretroviral therapy (ART). The Cost-effectiveness of Preventing AIDS Complications model was employed to determine the clinical impact and cost-effectiveness of baseline genotype vs no baseline genotype for people starting ART with dolutegravir (DTG) and an NRTI pair. Baseline genotype does not alter regimen selection for people with no TDR (83.8%). Baseline genotype consequent to <1 additional undiscounted quality-adjusted life-day, cost an additional $500/person, and was not cost-effective (incremental cost-effectiveness ratio: $420 000/quality-adjusted life-year) compared with no baseline genotype. Findings suggest minimal clinical benefit of baseline genotype and its no cost-effectiveness with INSTI-based first-line regimens in the United States. Cost-effectiveness of baseline genotype was observed at current TDR prevalence only under unlikely conditions, eg, DTG-based regimens achieving ≤ 50% suppression of transmitted NRTI resistance.