Comparison of HIV resistance-associated mutations detected when analysed by conventional sequencing techniques (population genotype) and when using the more sensitive method of clonal analysis to analyse HIV-1 isolated at the baseline (pre-therapy) visit and virological failure (VF) for the 14 subjects who met VF criteria in COL40263
| . | Pre-therapy baseline sample . | VF sample . | |||||
|---|---|---|---|---|---|---|---|
| Subject . | HIV RNA log10 copies/mL . | population genotype . | clonal genotypea . | timepoint . | HIV RNA log10 copies/mL . | population genotype . | clonal genotypea . |
| 1 | 5.25 | WT | WT (17/17) | week 32 | 2.77 | K65K/R | K65R (16/61) |
| K65R + S68N (20/61) | |||||||
| K65R + Y115F (25/61) | |||||||
| 3.52 | Additional (post-VF) clonal analysis ∼at week 36 WT (6/23) | ||||||
| K65R + S68N (10/23) | |||||||
| K65R (2/23) | |||||||
| K65R + Y115F (3/23) | |||||||
| D67N + L210W + T215F (1/23) | |||||||
| T215A (1/23) | |||||||
| 2 | 5.3 | WT | WT (58/105) | week 48 | 2.87 | K65R + S68N/S + Y115F/Y + V118I | K65R + Y115F (6/48) |
| M184V (1/105) | K65R + S68N (16/48) | ||||||
| K70E (1/105) | K65R + S68N + Y115F (26/48) | ||||||
| V118I (45/105) | |||||||
| 3 | 5.85 | WT | WT (33/33) | week 32 | 3.36 | D67N + K70R + M184V | WT (7/46) |
| V118I (8/46) | |||||||
| D67N + K70R + M184V (18/46) | |||||||
| D67N + K70R + M184V + K219E (10/46) | |||||||
| D67N + K70R + M184V + K219Q (3/46) | |||||||
| 4 | 6.11 | WT | WT (77/77) | week 32 | 4.55 | T215Y | WT (7/74) |
| T215Y (63/74) | |||||||
| T215Y + M41L (4/74) | |||||||
| 5 | 5.34 | K103K/N + Y188F/H/L/Y | WT (8/30) | week 32 | 4.23 | M41L + D67N + K70R + M184V + T215F + K219E | WT (11/50) |
| Y188L (7/30) | M41L + D67N + K70R + Y188L + M184V + T215F + K219E (34/50) | ||||||
| K103N (13/30) | M41L + D67N + K70R + Y188L + M184V + T215L + K219E (1/50) | ||||||
| K103N + T215A (2/30) | Y188L (3/50) | ||||||
| M41L + D67N + K70R + Y188L (1/50) | |||||||
| 6 | 5.18 | WT | WT (127/128) | week 24 | 4.15 | WT | WT (31/31) |
| T215S (1/128) | |||||||
| 7 | 5.72 | WT | WT (53/53) | week 32 | 3.59 | M184V | M184V (36/62) |
| M184V + D67G (1/62) | |||||||
| D67N + T215F (21/62) | |||||||
| M184V + T215S (1/62) | |||||||
| D67N + K70R + T215Y (1/62) | |||||||
| D67N + S68G + T215Y (1/62) | |||||||
| K65R + S68N + Y115F + V118I (1/62) | |||||||
| 8 | 4.4 | WT | WT (44/46) | week 32 | 2.68 | WT | WT (35/36) |
| K219Q (2/46) | L210W (1/36) | ||||||
| 9 | 5.84 | T215T/A | WT (47/56) | week 28 | 5.08 | D67N + L210L/W + T215F | D67N + T215F (64/92) |
| D67G (1/56) | D67N + K70R + T215F (13/92) | ||||||
| T215A (8/56) | D67N + M184V + T215F (2/92) | ||||||
| D67N + L210W + T215F (13/92) | |||||||
| 10 | 5.30 | WT | WT (68/73) | week 24 | 3.54 | D67N + K70K/R + T215F | M184V + T215F (1/64) |
| M41I (1/73) | D67N + T215F (36/64) | ||||||
| K103R (1/73) | D67N + T215Y (1/64) | ||||||
| Y181H (1/73) | M41L + D67N + T215F (6/64) | ||||||
| M184V (1/73) | M41V + D67N + T215F (1/64) | ||||||
| G190E (1/73) | M41V + D67N + G190E + T215F (1/64) | ||||||
| A62T + D67N + T215F (1/64) | |||||||
| D67N + K70R + T215F (12/64) | |||||||
| D67N + K70R + M184V (1/64) | |||||||
| D67N + G190E + T215F (1/64) | |||||||
| D67N + K70T + T215F (1/64) | |||||||
| D67N + T215F + K219T (2/64) | |||||||
| 11 | 5.11 | WT | WT (13/13) | week 40 | 2.8 | D67N + K70R + M184V | WT (10/16) |
| D67N + K70R + 184V (1/16) | |||||||
| D67N + M184V (1/16) | |||||||
| D67N + K70R + M184V + K219E (4/16) | |||||||
| 12 | 4.72 | WT | WT (49/58) | week 24 | 4.2 | WT | WT (56/57) |
| Y188L (9/58) | Y188L (1/57) | ||||||
| 13 | 5.54 | WT | WT (66/67) | week 40 | 4.6 | WT | WT (30/31) |
| F77L (1/67) | M184I (1/31) | ||||||
| 14 | 5.56 | WT | WT (56/60) | week 24 | 5.66 | M41L/M + D67D/N + L210L/W + T215F | T215F (1/34) |
| A62V (2/60) | M41L + T215F (3/34) | ||||||
| D67G (1/60) | D67N + T215F (26/34) | ||||||
| M184V (1/60) | D67N + S68G + L210W + T215F (1/34) | ||||||
| D67N + K70R + T215F (2/34) | |||||||
| D67N + L210W + T215F (1/34) | |||||||
| . | Pre-therapy baseline sample . | VF sample . | |||||
|---|---|---|---|---|---|---|---|
| Subject . | HIV RNA log10 copies/mL . | population genotype . | clonal genotypea . | timepoint . | HIV RNA log10 copies/mL . | population genotype . | clonal genotypea . |
| 1 | 5.25 | WT | WT (17/17) | week 32 | 2.77 | K65K/R | K65R (16/61) |
| K65R + S68N (20/61) | |||||||
| K65R + Y115F (25/61) | |||||||
| 3.52 | Additional (post-VF) clonal analysis ∼at week 36 WT (6/23) | ||||||
| K65R + S68N (10/23) | |||||||
| K65R (2/23) | |||||||
| K65R + Y115F (3/23) | |||||||
| D67N + L210W + T215F (1/23) | |||||||
| T215A (1/23) | |||||||
| 2 | 5.3 | WT | WT (58/105) | week 48 | 2.87 | K65R + S68N/S + Y115F/Y + V118I | K65R + Y115F (6/48) |
| M184V (1/105) | K65R + S68N (16/48) | ||||||
| K70E (1/105) | K65R + S68N + Y115F (26/48) | ||||||
| V118I (45/105) | |||||||
| 3 | 5.85 | WT | WT (33/33) | week 32 | 3.36 | D67N + K70R + M184V | WT (7/46) |
| V118I (8/46) | |||||||
| D67N + K70R + M184V (18/46) | |||||||
| D67N + K70R + M184V + K219E (10/46) | |||||||
| D67N + K70R + M184V + K219Q (3/46) | |||||||
| 4 | 6.11 | WT | WT (77/77) | week 32 | 4.55 | T215Y | WT (7/74) |
| T215Y (63/74) | |||||||
| T215Y + M41L (4/74) | |||||||
| 5 | 5.34 | K103K/N + Y188F/H/L/Y | WT (8/30) | week 32 | 4.23 | M41L + D67N + K70R + M184V + T215F + K219E | WT (11/50) |
| Y188L (7/30) | M41L + D67N + K70R + Y188L + M184V + T215F + K219E (34/50) | ||||||
| K103N (13/30) | M41L + D67N + K70R + Y188L + M184V + T215L + K219E (1/50) | ||||||
| K103N + T215A (2/30) | Y188L (3/50) | ||||||
| M41L + D67N + K70R + Y188L (1/50) | |||||||
| 6 | 5.18 | WT | WT (127/128) | week 24 | 4.15 | WT | WT (31/31) |
| T215S (1/128) | |||||||
| 7 | 5.72 | WT | WT (53/53) | week 32 | 3.59 | M184V | M184V (36/62) |
| M184V + D67G (1/62) | |||||||
| D67N + T215F (21/62) | |||||||
| M184V + T215S (1/62) | |||||||
| D67N + K70R + T215Y (1/62) | |||||||
| D67N + S68G + T215Y (1/62) | |||||||
| K65R + S68N + Y115F + V118I (1/62) | |||||||
| 8 | 4.4 | WT | WT (44/46) | week 32 | 2.68 | WT | WT (35/36) |
| K219Q (2/46) | L210W (1/36) | ||||||
| 9 | 5.84 | T215T/A | WT (47/56) | week 28 | 5.08 | D67N + L210L/W + T215F | D67N + T215F (64/92) |
| D67G (1/56) | D67N + K70R + T215F (13/92) | ||||||
| T215A (8/56) | D67N + M184V + T215F (2/92) | ||||||
| D67N + L210W + T215F (13/92) | |||||||
| 10 | 5.30 | WT | WT (68/73) | week 24 | 3.54 | D67N + K70K/R + T215F | M184V + T215F (1/64) |
| M41I (1/73) | D67N + T215F (36/64) | ||||||
| K103R (1/73) | D67N + T215Y (1/64) | ||||||
| Y181H (1/73) | M41L + D67N + T215F (6/64) | ||||||
| M184V (1/73) | M41V + D67N + T215F (1/64) | ||||||
| G190E (1/73) | M41V + D67N + G190E + T215F (1/64) | ||||||
| A62T + D67N + T215F (1/64) | |||||||
| D67N + K70R + T215F (12/64) | |||||||
| D67N + K70R + M184V (1/64) | |||||||
| D67N + G190E + T215F (1/64) | |||||||
| D67N + K70T + T215F (1/64) | |||||||
| D67N + T215F + K219T (2/64) | |||||||
| 11 | 5.11 | WT | WT (13/13) | week 40 | 2.8 | D67N + K70R + M184V | WT (10/16) |
| D67N + K70R + 184V (1/16) | |||||||
| D67N + M184V (1/16) | |||||||
| D67N + K70R + M184V + K219E (4/16) | |||||||
| 12 | 4.72 | WT | WT (49/58) | week 24 | 4.2 | WT | WT (56/57) |
| Y188L (9/58) | Y188L (1/57) | ||||||
| 13 | 5.54 | WT | WT (66/67) | week 40 | 4.6 | WT | WT (30/31) |
| F77L (1/67) | M184I (1/31) | ||||||
| 14 | 5.56 | WT | WT (56/60) | week 24 | 5.66 | M41L/M + D67D/N + L210L/W + T215F | T215F (1/34) |
| A62V (2/60) | M41L + T215F (3/34) | ||||||
| D67G (1/60) | D67N + T215F (26/34) | ||||||
| M184V (1/60) | D67N + S68G + L210W + T215F (1/34) | ||||||
| D67N + K70R + T215F (2/34) | |||||||
| D67N + L210W + T215F (1/34) | |||||||
NRTI resistance mutations are shown in bold and WT indicates wild-type HIV. For Subject 1, clonal analysis results are also presented for an additional post-VF timepoint.
aClonal variant abundance is expressed as the number of clones with that genotype/total number of clones analysed from that sample.
Comparison of HIV resistance-associated mutations detected when analysed by conventional sequencing techniques (population genotype) and when using the more sensitive method of clonal analysis to analyse HIV-1 isolated at the baseline (pre-therapy) visit and virological failure (VF) for the 14 subjects who met VF criteria in COL40263
| . | Pre-therapy baseline sample . | VF sample . | |||||
|---|---|---|---|---|---|---|---|
| Subject . | HIV RNA log10 copies/mL . | population genotype . | clonal genotypea . | timepoint . | HIV RNA log10 copies/mL . | population genotype . | clonal genotypea . |
| 1 | 5.25 | WT | WT (17/17) | week 32 | 2.77 | K65K/R | K65R (16/61) |
| K65R + S68N (20/61) | |||||||
| K65R + Y115F (25/61) | |||||||
| 3.52 | Additional (post-VF) clonal analysis ∼at week 36 WT (6/23) | ||||||
| K65R + S68N (10/23) | |||||||
| K65R (2/23) | |||||||
| K65R + Y115F (3/23) | |||||||
| D67N + L210W + T215F (1/23) | |||||||
| T215A (1/23) | |||||||
| 2 | 5.3 | WT | WT (58/105) | week 48 | 2.87 | K65R + S68N/S + Y115F/Y + V118I | K65R + Y115F (6/48) |
| M184V (1/105) | K65R + S68N (16/48) | ||||||
| K70E (1/105) | K65R + S68N + Y115F (26/48) | ||||||
| V118I (45/105) | |||||||
| 3 | 5.85 | WT | WT (33/33) | week 32 | 3.36 | D67N + K70R + M184V | WT (7/46) |
| V118I (8/46) | |||||||
| D67N + K70R + M184V (18/46) | |||||||
| D67N + K70R + M184V + K219E (10/46) | |||||||
| D67N + K70R + M184V + K219Q (3/46) | |||||||
| 4 | 6.11 | WT | WT (77/77) | week 32 | 4.55 | T215Y | WT (7/74) |
| T215Y (63/74) | |||||||
| T215Y + M41L (4/74) | |||||||
| 5 | 5.34 | K103K/N + Y188F/H/L/Y | WT (8/30) | week 32 | 4.23 | M41L + D67N + K70R + M184V + T215F + K219E | WT (11/50) |
| Y188L (7/30) | M41L + D67N + K70R + Y188L + M184V + T215F + K219E (34/50) | ||||||
| K103N (13/30) | M41L + D67N + K70R + Y188L + M184V + T215L + K219E (1/50) | ||||||
| K103N + T215A (2/30) | Y188L (3/50) | ||||||
| M41L + D67N + K70R + Y188L (1/50) | |||||||
| 6 | 5.18 | WT | WT (127/128) | week 24 | 4.15 | WT | WT (31/31) |
| T215S (1/128) | |||||||
| 7 | 5.72 | WT | WT (53/53) | week 32 | 3.59 | M184V | M184V (36/62) |
| M184V + D67G (1/62) | |||||||
| D67N + T215F (21/62) | |||||||
| M184V + T215S (1/62) | |||||||
| D67N + K70R + T215Y (1/62) | |||||||
| D67N + S68G + T215Y (1/62) | |||||||
| K65R + S68N + Y115F + V118I (1/62) | |||||||
| 8 | 4.4 | WT | WT (44/46) | week 32 | 2.68 | WT | WT (35/36) |
| K219Q (2/46) | L210W (1/36) | ||||||
| 9 | 5.84 | T215T/A | WT (47/56) | week 28 | 5.08 | D67N + L210L/W + T215F | D67N + T215F (64/92) |
| D67G (1/56) | D67N + K70R + T215F (13/92) | ||||||
| T215A (8/56) | D67N + M184V + T215F (2/92) | ||||||
| D67N + L210W + T215F (13/92) | |||||||
| 10 | 5.30 | WT | WT (68/73) | week 24 | 3.54 | D67N + K70K/R + T215F | M184V + T215F (1/64) |
| M41I (1/73) | D67N + T215F (36/64) | ||||||
| K103R (1/73) | D67N + T215Y (1/64) | ||||||
| Y181H (1/73) | M41L + D67N + T215F (6/64) | ||||||
| M184V (1/73) | M41V + D67N + T215F (1/64) | ||||||
| G190E (1/73) | M41V + D67N + G190E + T215F (1/64) | ||||||
| A62T + D67N + T215F (1/64) | |||||||
| D67N + K70R + T215F (12/64) | |||||||
| D67N + K70R + M184V (1/64) | |||||||
| D67N + G190E + T215F (1/64) | |||||||
| D67N + K70T + T215F (1/64) | |||||||
| D67N + T215F + K219T (2/64) | |||||||
| 11 | 5.11 | WT | WT (13/13) | week 40 | 2.8 | D67N + K70R + M184V | WT (10/16) |
| D67N + K70R + 184V (1/16) | |||||||
| D67N + M184V (1/16) | |||||||
| D67N + K70R + M184V + K219E (4/16) | |||||||
| 12 | 4.72 | WT | WT (49/58) | week 24 | 4.2 | WT | WT (56/57) |
| Y188L (9/58) | Y188L (1/57) | ||||||
| 13 | 5.54 | WT | WT (66/67) | week 40 | 4.6 | WT | WT (30/31) |
| F77L (1/67) | M184I (1/31) | ||||||
| 14 | 5.56 | WT | WT (56/60) | week 24 | 5.66 | M41L/M + D67D/N + L210L/W + T215F | T215F (1/34) |
| A62V (2/60) | M41L + T215F (3/34) | ||||||
| D67G (1/60) | D67N + T215F (26/34) | ||||||
| M184V (1/60) | D67N + S68G + L210W + T215F (1/34) | ||||||
| D67N + K70R + T215F (2/34) | |||||||
| D67N + L210W + T215F (1/34) | |||||||
| . | Pre-therapy baseline sample . | VF sample . | |||||
|---|---|---|---|---|---|---|---|
| Subject . | HIV RNA log10 copies/mL . | population genotype . | clonal genotypea . | timepoint . | HIV RNA log10 copies/mL . | population genotype . | clonal genotypea . |
| 1 | 5.25 | WT | WT (17/17) | week 32 | 2.77 | K65K/R | K65R (16/61) |
| K65R + S68N (20/61) | |||||||
| K65R + Y115F (25/61) | |||||||
| 3.52 | Additional (post-VF) clonal analysis ∼at week 36 WT (6/23) | ||||||
| K65R + S68N (10/23) | |||||||
| K65R (2/23) | |||||||
| K65R + Y115F (3/23) | |||||||
| D67N + L210W + T215F (1/23) | |||||||
| T215A (1/23) | |||||||
| 2 | 5.3 | WT | WT (58/105) | week 48 | 2.87 | K65R + S68N/S + Y115F/Y + V118I | K65R + Y115F (6/48) |
| M184V (1/105) | K65R + S68N (16/48) | ||||||
| K70E (1/105) | K65R + S68N + Y115F (26/48) | ||||||
| V118I (45/105) | |||||||
| 3 | 5.85 | WT | WT (33/33) | week 32 | 3.36 | D67N + K70R + M184V | WT (7/46) |
| V118I (8/46) | |||||||
| D67N + K70R + M184V (18/46) | |||||||
| D67N + K70R + M184V + K219E (10/46) | |||||||
| D67N + K70R + M184V + K219Q (3/46) | |||||||
| 4 | 6.11 | WT | WT (77/77) | week 32 | 4.55 | T215Y | WT (7/74) |
| T215Y (63/74) | |||||||
| T215Y + M41L (4/74) | |||||||
| 5 | 5.34 | K103K/N + Y188F/H/L/Y | WT (8/30) | week 32 | 4.23 | M41L + D67N + K70R + M184V + T215F + K219E | WT (11/50) |
| Y188L (7/30) | M41L + D67N + K70R + Y188L + M184V + T215F + K219E (34/50) | ||||||
| K103N (13/30) | M41L + D67N + K70R + Y188L + M184V + T215L + K219E (1/50) | ||||||
| K103N + T215A (2/30) | Y188L (3/50) | ||||||
| M41L + D67N + K70R + Y188L (1/50) | |||||||
| 6 | 5.18 | WT | WT (127/128) | week 24 | 4.15 | WT | WT (31/31) |
| T215S (1/128) | |||||||
| 7 | 5.72 | WT | WT (53/53) | week 32 | 3.59 | M184V | M184V (36/62) |
| M184V + D67G (1/62) | |||||||
| D67N + T215F (21/62) | |||||||
| M184V + T215S (1/62) | |||||||
| D67N + K70R + T215Y (1/62) | |||||||
| D67N + S68G + T215Y (1/62) | |||||||
| K65R + S68N + Y115F + V118I (1/62) | |||||||
| 8 | 4.4 | WT | WT (44/46) | week 32 | 2.68 | WT | WT (35/36) |
| K219Q (2/46) | L210W (1/36) | ||||||
| 9 | 5.84 | T215T/A | WT (47/56) | week 28 | 5.08 | D67N + L210L/W + T215F | D67N + T215F (64/92) |
| D67G (1/56) | D67N + K70R + T215F (13/92) | ||||||
| T215A (8/56) | D67N + M184V + T215F (2/92) | ||||||
| D67N + L210W + T215F (13/92) | |||||||
| 10 | 5.30 | WT | WT (68/73) | week 24 | 3.54 | D67N + K70K/R + T215F | M184V + T215F (1/64) |
| M41I (1/73) | D67N + T215F (36/64) | ||||||
| K103R (1/73) | D67N + T215Y (1/64) | ||||||
| Y181H (1/73) | M41L + D67N + T215F (6/64) | ||||||
| M184V (1/73) | M41V + D67N + T215F (1/64) | ||||||
| G190E (1/73) | M41V + D67N + G190E + T215F (1/64) | ||||||
| A62T + D67N + T215F (1/64) | |||||||
| D67N + K70R + T215F (12/64) | |||||||
| D67N + K70R + M184V (1/64) | |||||||
| D67N + G190E + T215F (1/64) | |||||||
| D67N + K70T + T215F (1/64) | |||||||
| D67N + T215F + K219T (2/64) | |||||||
| 11 | 5.11 | WT | WT (13/13) | week 40 | 2.8 | D67N + K70R + M184V | WT (10/16) |
| D67N + K70R + 184V (1/16) | |||||||
| D67N + M184V (1/16) | |||||||
| D67N + K70R + M184V + K219E (4/16) | |||||||
| 12 | 4.72 | WT | WT (49/58) | week 24 | 4.2 | WT | WT (56/57) |
| Y188L (9/58) | Y188L (1/57) | ||||||
| 13 | 5.54 | WT | WT (66/67) | week 40 | 4.6 | WT | WT (30/31) |
| F77L (1/67) | M184I (1/31) | ||||||
| 14 | 5.56 | WT | WT (56/60) | week 24 | 5.66 | M41L/M + D67D/N + L210L/W + T215F | T215F (1/34) |
| A62V (2/60) | M41L + T215F (3/34) | ||||||
| D67G (1/60) | D67N + T215F (26/34) | ||||||
| M184V (1/60) | D67N + S68G + L210W + T215F (1/34) | ||||||
| D67N + K70R + T215F (2/34) | |||||||
| D67N + L210W + T215F (1/34) | |||||||
NRTI resistance mutations are shown in bold and WT indicates wild-type HIV. For Subject 1, clonal analysis results are also presented for an additional post-VF timepoint.
aClonal variant abundance is expressed as the number of clones with that genotype/total number of clones analysed from that sample.
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