Phenotypic or genotypic resistance testing for choosing antiretroviral therapy after treatment failure: a randomized trial

TLDR

The study aimed to compare the effectiveness of phenotypic, genotypic, and standard‑of‑care resistance testing for selecting antiretroviral therapy after protease inhibitor failure. Patients with high viral load were randomized to receive phenotypic testing, genotypic testing, or standard care. Across all participants, resistance assays did not improve virologic outcomes compared with standard care, although among patients with limited prior PI exposure, genotypic testing led to higher rates of viral suppression.

Abstract

Objective To assess the respective value of phenotype versus genotype versus standard of care for choosing antiretroviral therapy in patients failing protease inhibitor-containing regimens. Methods Patients with plasma HIV-1 RNA exceeding 1000 copies/ml were randomly allocated to phenotyping, genotyping, or standard of care. Results Five-hundred and forty-one patients were randomized, 190 to phenotyping, 192 to genotyping and 159 to standard of care. The baseline median CD4 cell count (280 × 106cells/l), the plasma HIV-1 RNA level (4.3 log10 copies/ml), and the number of drugs previously received (n = 6) were similar in the three arms. More patients in the standard-of-care arm received at least three new drugs (55% versus 20% in the other arms;P < 0.001) and a regimen containing drugs from the three different classes. Plasma HIV-1 RNA was < 200 copies/ml at week 12 in 35% of patients in the phenotyping arm, 44% in the genotyping arm and 36% in the standard-of-care arm (phenotyping versus standard of care, P = 0.918; genotyping versus standard of care, P = 0.120). In a secondary analysis of 179 patients experiencing a first protease inhibitor failure, the percentage of patients achieving HIV-1 RNA < 200 copies/ml was significantly higher in the genotyping arm (65%) than in the phenotyping (45%) and the standard-of-care arms (45%) (genotyping versus standard of care, P = 0.022). Conclusions Overall, resistance assays did not demonstrate benefit over standard of care. In patients with the most limited protease inhibitor experience, a significant benefit was observed in the genotyping arm.