Pharmacodynamic and pharmacokinetic parameters.

IC50 [nM] and m [unit less] values are available from single turnover experiments in primary peripheral blood mononuclear cells supplemented with 50% human serum from Shen et al. [40], Laskey et al. [92] (DTG) and Jilek at al. [93] (MVC). Because some compounds are highly protein bound, IC50 values had to be adjusted for protein binding as outlined in the S5 Text. Indicated values are after protein adjustment. IC50 values are reported to be log normal distributed and m values to be normal distributed [40, 93] with respective coefficients of variation CV = 100 ⋅ σ/μ [%]. Parameters Cmin and Cmax refer to the minimum and maximum concentrations in [nM] during chronic administration using the standard dosing regimen, taken from Shen et al. [40] except those for DTG [94], RPV [95] and MVC [96] (150mg twice daily). t1/2—half life of the drug in [hr], fb—fraction of the drug bound to plasma proteins in [%]. +These values were fixed to the typical parameter distributions observed for all other compounds. ⋄Parameters were taken from Drug Bank when available https://www.drugbank.ca/, accession numbers: DB04835, DB00625, DB00238, DB00705, DB08864, DB06817, DB09101, DB08930, DB01072, DB00701, DB01264, DB00224, DB00220, DB00932 or ♭PubChem https://pubchem.ncbi.nlm.nih.gov, id: 92727. When parameters were not readily available in these databases, parameters were obtained from the indicated literature source. MVC -maraviroc, EFV -efavirenz, NVP -nevirapine, DLV -delavirine, ETR -etravirine, RPV -rilpivirine, RAL -raltegravir, EVG -elvitegravir, DTG -dolutegravir, ATV -atazanavir, APV -amprenavir, DRV -darunavir, IDV -indinavir, LPV -lopinavir, NFV -nelfinavir, SQV -saquinavir, TPV -tipranavir.