Table 2.
Comparison of Population Genotypic Results to Genotypic Results Obtained by Clonal Analysis at Baseline and the Failure Time Points for the Seven Patients Meeting VF Criteriaa
| |
Baseline |
On therapy/virologic failure |
||||
|---|---|---|---|---|---|---|
| Patient | Phenotype | Population genotype | Clonal analysis | Phenotype | Population genotype | Clonal analysis |
| FPV/r-1b | FPV FC = 3.8 | RT: L210W + T215C; PR: M46I + L76V |
RT:L210W, T215C; PR: M46I, L76V (50/53) |
FPV FC = 3.0 | RT: M184V,L210W + T215C | RT: M184V,L210W, T215C; PR: M46I, I54M or L,L76V (48/55) |
| TDF FC = 1.0 | TDF FC = 0.6 | |||||
| FTC FC = 1.5 | RT: M41L,L210W, T215C; PR: M46I, L76V (1/53) RT: L210W, T215C or Y; PR: M46I, L76V (2/53) |
FTC FC = 78 | PR: M46I, I54I/L/M,L76V | RT: M184V,L210W, T215C; PR: M46I, I47V (1/55) RT: M184V,L210W, T215C; PR: M46I, L76V(2/55) WT (1/55) RT: M184V, L210W, T215C; PR:M46I,I47V,L76V (3/55) |
||
| FPV/r-2 | FPV FC = 1.4 | WT | WT (53/58) | FPV FC = 1.3 | RT: M41L, M184V,L210W, T215S/Y; PR: WT | RT: M41L, M184V,T215Y; PR: WT (1/51) |
| TDF FC = 0.8 | RT:Y181I + 215P + 236L; PR:WT (1/58) |
TDF FC = 1.8 | RT: M41L, M184V,L210W, T215Y; PR: WT(39/51) | |||
| FTC FC = 1.1 | RT: L210W, T215Y; PR:WT (1/58) RT: M41L; PR: WT (3/58) |
3TC FC > MAX | RT: M184V, PR: WT (8/51) RT: K103N, M184V, P225H; PR: WT (2/51) RT: Y181C, M184V; PR: WT (1/51) |
|||
| FPV/r-3 | FPV FC = 2.2 | WT | WT (48/50) | FPV FC = 38 | RT: M184V | RT: M184V; PR:M46I + I50V (54/58) |
| TDF FC = 0.9 | RT: K65R, K70R; PR: WT (1/50) |
TDF FC = 0.5 | PR: M46I, I50V | RT: M184V + Y188H; PR:M46I + I50V (1/58) |
||
| FTC FC = 0.8 | RT: Y188C; PR: WT (1/50) |
FTC FC = 76 | RT: D67N + M184V; PR:M46I + I50V (1/58) RT: M184V; PR:L33F + M46I + I50V (1/58) RT: M184V; P225H; PR:M46I + I50V (1/58) |
|||
| FPV/r-4 | FPV FC = 0.8 | WT | WT (51/53) | FPV FC = 19 | RT: K65R, D67N | RT: K65R; PR:V32I, M46I,I47V (35/55) |
| TDF FC = 0.7 | RT: WT, PR:N88S (1/53) | TDF FC = 1.8 | PR: V32I, M46I, | RT: K65R; PR:V32I,I47V (1/55) | ||
| FTC FC = 0.7 | RT: WT, PR: I47V (1/53) | FTC FC = 8.5 | I47V | RT: K65R, M184I or V; PR:V32I, M46I,I47V (5/55) RT: K65R, D67N; PR:V32I, M46I,I47V (14/55) |
||
| ATV/r-1 | ATV FC = 1.2 | WT | WT (51/52) | ATV FC = 1.0 | RT: M184V, | WT (34/60) |
| TDF FC = 1.0 | RT: WT; PR: N88S(1/52) | TDF FC = 0.6 | PR: WT | RT: D67N; PR: WT (1/60) | ||
| FTC FC = 1.1 | FTC FC = 18 | RT: WT; PR: V82A; (1/60) RT: M184V; PR: WT (24/60) |
||||
| ATV/r-2 | ATV FC = 1.2 | WT | WT (49/55) | ATV FC = 3.9 | WT | WT (52/52) |
| TDF FC = 0.9 | RT: K65R; PR: WT (1/55) | TDF FC = 0.8 | ||||
| FTC FC = 1.2 | RT: WT; PR:V82S (1/55) RT: T215P, P236L; PR:WT (1/55) RT: WT; PR: I84V (2/55) RT: Y181C; PR: WT (1/55) |
FTC FC = 0.9 | ||||
| ATV/r-3 | ATV FC = 0.9 | WT | WT (48/50) | ATV FC = 2.1 | WT | WT (56/59) |
| TDF FC = 1.1 | RT: T215P, P236L; PR:WT (5/50) |
TDF FC = 1.1 | RT: T215R, P236L; PR: WT (2/59) | |||
| FTC FC = 1.0 | RT: P236L; PR WT (1/50) | FTC FC = 1.1 | RT: V106A; PR: WT (1/59) | |||
Major IAS-USA-defined resistance-associated mutations or TAMs reversion mutations are shown and IAS-USA-defined mutations associated with resistance to the specific study regimen are in bold. Minor IAS-USA-defined protease mutations are not shown. Mutations detected at baseline by either method that were also present at the failure time points are underlined. Population phenotypic susceptibility fold-changes (FC) for the study drug regimen are also presented; phenotypic results that exceed the Monogram lower limit cut-offs for reduced susceptibility (TDF: 1.4 FC; FTC: 3.5 FC; ATV: 2.2 FC; and FPV: 2.0 FC) are in bold and underlined. A minimum of 50 clones was analyzed at each time point; the number of clones with that genotype for that sample is shown in parentheses after each genotype.
Patient FPV/r-1 is Patient 1 as described in Table 1. Week 12 on-therapy results compared (insufficient week 24 sample was available for clonal analysis); all other CG and PG obtained at VF.