Lataillade M, et al. - Researchers performed AI438011 (a randomized, phase 2b, dose-finding study in HIV-1–infected, treatment-experienced subjects) to investigate the safety, efficacy, and dose–response of fostemsavir vs ritonavir-boosted atazanavir (ATV/r). They observed that regardless of baseline (BL) nucleoside reverse transcriptase inhibitor, nonnucleoside reverse transcriptase inhibitor, and protease inhibitor resistance-associated mutations, response rates remained similar across study arms. Compared with ATV/r, emergent changes in viral susceptibility were more frequently observed with fostemsavir.

Methods

• Researchers administered fostemsavir or ATV/r, each with tenofovir disoproxil fumarate + raltegravir, to 251 treatment-experienced subjects with baseline (BL) susceptibility to study drugs [temsavir half-maximal inhibitory concentration (IC50) <100 nM, PhenoSense Entry assay].
• They assessed subjects meeting resistance-testing criteria for emergent viral drug resistance.
• For this study, changes in temsavir IC50 from BL was given a conservative technical cutoff (>3-fold increase).

Results

• Resistance testing was performed on 66/200 fostemsavir and 14/51 ATV/r subjects; 44/66 and 9/14 were successfully tested using the PhenoSense GT assay.
• Emergent tenofovir disoproxil fumarate or ATV resistance was not reported among the subjects.
• Emergent raltegravir resistance developed in 6 fostemsavir-treated subjects.
• In this study, 29/66 fostemsavir-treated subjects demonstrated an evaluable phenotype using PhenoSense Entry (which tests for viral susceptibility to temsavir) and 13/29 exhibited >3-fold increase in temsavir IC₅₀ from BL.
• In 11/13 subjects, gp120 population sequencing was successful; 7 showed emergent substitutions in gp120 associated with reduced temsavir susceptibility (S375, M426, or M434).
• However, before the week 48 database lock, 5/13 fostemsavir-treated subjects achieved subsequent suppression to <50 copies/mL; this was observed regardless of key gp120 substitutions.