Figure 3

NRTI susceptibilities and replicative capacity associated with RT domains of patient P66. (A) Schematic representation of full-length and chimeras of subtype C wild-type and patient-derived RT gag-pol expressing vectors used for drug susceptibility and replicative capacity testing. The positions of the restriction sites used for cloning of patient-derived PR-RT fragments (ApaI and ClaI) and for RT domain swapping (HpaI and SpeI) are indicated above the vector. The origins of the RT domains are shown as different coloured boxes: black, wild-type virus; dark gray, patient-derived RT at 4 months; light gray, patient-derived RT at 17 months; and white, patient-derived RT at 37 months. The names of the vectors are indicated on the right with a number representing the month when the sample was collected followed by the patient-derived domain(s) being expressed. Mutations present in each domain are shown on the full-length RT constructs as follows: inside the box, NRTI-associated resistance mutations; above the box, NNRTI-associated resistance mutations; and below the box, other mutations. Pol, DNA pol domain; Cn, Connection subdomain; Rh, RNase H domain. (B) Susceptibility to d4T exhibited by patient-derived full-length RTs and RT domains. (C) Susceptibility to second-line NRTI ABC exhibited by patient-derived full-length RTs. (D) Susceptibility to second-line NRTI ddI exhibited by patient-derived full-length RTs. (E) Susceptibility to TDF exhibited by patient-derived full-length RTs. (F) Replicative capacities relative to virus expressing full-length patient-derived RT from 4-months after initiation of therapy, set at 100%, are shown for each virus. The error bars represent standard error of the mean of three or more independent experiments.