Table 1.
Treatment-Emergent Resistance by DTG Regimen.
| Publication | DTG Regimen | People on DTG Regimen, N |
GRT Results (Historical and/or Baseline), n/N (%) | People with Baseline or Historical Mutations, n/N (%) [Mutations] | VF Outcomes, n/N (%) | |||
|---|---|---|---|---|---|---|---|---|
| Total People with VF |
GRT Availability at VF |
People with Baseline Mutations and VF | People with Emergent Integrase Mutations at VF [Mutations] | |||||
| DTG Monotherapy | ||||||||
| Rojas et al., 2016 [50] | DTG monotherapy | 33 | 33/33 (100) | 16/33 (48) [15V, M41L, E44D, A62V, K65R, D67N, T69D, K70R, L74V, Y115F, V118I, M184V, L210W/S, T215Y/F, K219E/Q, M46I/L, I50L, L63P, A71V, G73S, V77I, L90M, A98G, K101E, K103N, V106A/I, V108I, Y181I/C, G190S] |
1/33 (3) | 1/1 (100) | 1/1 (100) | 1/1 (100) [G118R] |
| Oldenbuettel et al., 2017 [49] | DTG monotherapy | 31 | NR | NR | 1/31 (3) | 1/1 (100) | NR | 1/1 (100) [Q148H, G140S] a |
| Tebano et al., 2020 [40] | DTG monotherapy | 61 | 61/61 (100) | 3/25 (12) [E138K, G140S, N155H, S147G, L74I] [63] b |
3/61 (5) | 3/3 (100) | 1/3 (33) [63] | 3/3 (100) [E138K, G140A, Q148R, E92Q, N155H] |
| 2DR with DTG | ||||||||
| Deschanvres et al., 2022 Dat’AIDS [37] |
DTG/RPV or DTG + XTC | 1374 | At least 6/1374 (<1) | At least 4/1374 (<1) [K103H/N/S/T, E138K, M184V] |
45/1374 (3) | 23/45 (51) | 4/45 (9) | 2/45 (4) [N155H, L74I] |
| Palmier et al., 2023 [39] | DTG/3TC | 358 | 358/358 | 17/358 (5) [M184V, K103N] c |
13/358 (4) | 9/13 (69) | 1/13 (8) | 1/13 (8) [R263K] |
| Bowman et al., 2023 [42] | DTG/3TC (majority), DTG/RPV, or DTG/FTC | 561 | 56/561 (10) | 2/561 (<1) [F121Y, N155H] b |
6/561 (1) | 5/6 (83) | 0 | 1/6 (17) [T66A, G118R, E138K] |
| 3DR with DTG | ||||||||
| Lepik et al., 2017 [43] | DTG + 3TC + ABC or DTG + TDF/FTC or TDF/3TC |
392 | 392/392 (100) d | NRTI: 31/392 (8) NNRTI: 40/392 (10) PI: 6/392 (2) INSTI: 3/392 (1) |
65/392 (17) | NR | NR | 3/65 (5) [T66I, R263K] |
| Schramm et al., 2022 [41] | TLD | 1892 | 89/1892 (5) | 53/1892 (3) [M184V/I, K65R, K70E, L74V/I, Y115F, M41L, D67N, K70R, L210W, T215Y/F, K219Q/E] |
37/1762 (2) | 14/37 (38) | 4/37 (11) | 2/37 (5) [R263K, G118R] |
| Diaz et al., 2023 [31] | TLD | 113 | NR | NR | 113/113 (100) e,f | 113/113 (100) | NR g | 25/113 (22) [M50I/T/M, V151A/I, L101I/V, R263K/R, G140R, G163R, T97A, L74I/M, E157Q, M154I, G118R, E138A, G149A/G, G193E] h |
| Kamori et al., 2023 [62] | DTG/TDF/3TC | 82 | NR | NR | 82/82 (100) e,i | 82/82 (100) e,i | 3/82 (4) j | 7/82 (9) [Q148K, E138K, G118R, G140A, T66A, R263K, T97A, Q95Q/K] h |
| Other | ||||||||
| Requena et al., 2017 [53] (HIV-2) |
DTG + DRV/r or DTG + ATV/r, plus 2 nucleos(t)ides | 5 | 5/5 (100) | 5/5 (100) [Y143G/C, Q91R/Q, E92E/Q, T97A/T, A119T, A153G/S, I84V, N155H] |
3/5 (60) | 3/3 (100) | 3/3 (100) | 3/3 (100) [K4R, K14R, V75A, G118R, A119T, V141I, Q148K/R, V150T, V151I, A153S, Q208H, L220F] |
| Castagna et al., 2018 [36] PRESTIGIO |
DTG 50 mg BID + OBT | 190 | 142/190 (75) | NNRTI: 80/142 (56) PI: 77/142 (54) INSTI: 117/142 (82) NRTI: 96/142 (68) |
48/190 (25) | 16/48 (33) k | 16/48 (33) | 9/48 (19) [T97A, E138K, L74I, G140S, Q148H, T66I] b,k |
| Steegen et al., 2019 [52] | Various | 4 | NR | NR | 4/4 (100) e | NR (assumed 100) | NR | 1/4 (25) [T66A, E138K, Y143R, S147G, Q95K, T97A] h |
| Scutari et al., 2020 [51] | Various | 13 | 13/13 (100) | 1/13 (8) [R263K] |
All regimens: 102/107 (95) | NR | NR | 3 [N155H, G140S, Q148H, E138A, T97A, Y143H/C/R] l |
| Seatla et al., 2021 [44] | Various | 24 (7 unknown, DTG- or RAL-based) | NR | NR | DTG: 24/24 (100) e
DTG or RAL: 7/7 (100) e |
NR | NR | 8/24 (33) [E138E/A/K/T, G140A, Q148R/K, A128T, G118R, S147G, E157Q, N155N/H/D, D232N, T66A] h |
| Gil et al., 2022 [47] | Various | NR m | NR | NR | NR m | NR m | NR | 8/174 (5) [G163R/K, S230R, R263K, E157Q] h,n |
| Landman et al., 2022 [38] COPEDOL |
Various (including monotherapy) |
459 | NRTI: 349/459 (76) NNRTI: 350/459 (76) PI: 349/459 (76) DTG: 150/459 (33) |
NRTI: 179/349 (51) NNRTI: 154/350 (44) PI: 139/349 (40) DTG: 9/150 (6) [V151L, R263K, E92Q, N155H, Q148H/K/R, L741I, G140A/C/S] |
94/440 (21) | 192/440 (44) | 14/440 (3) | 5/440 (1) [E138A/K/T, G140A/C/S, T66K + L74M, S153F, E157Q] o |
| Abdullahi et al., 2023 [46] | Various | 4263 | NR | NR | 281/4263 (7) p | 33/281 (12; all DTG + 3TC + TDF) |
NR | 1/281 (<1) [T66A, G118R, E138K, R263K] h |
| Armenia et al., 2023 [35] | Various (including monotherapy) | 467 | NR | NR | 467/467 (100) e | 467/467 (100) e | NR | Total: 58/467 (12) INSTI-naive: n = 9 (2) g INSTI-experienced: n = 46 (10) h [N155H, R263K, E138A/K/T, S147G, E92A/Q, G140A/C/S, Q148H/R, D232N, T97A, T66A/I, G118R, L74I, V151A/I, E157Q, L74M, G163R, S153F, H51Y, P142T, Y143S, G149A] |
| Loosli et al., 2023 [48] | Various (including monotherapy) | 599 | 395/599 (66) | NR | 599/599 (100) e | NR | NR | 86/599 (14) h
INSTI-naive: n = 28 (5) g [T66A/I/K/R, E92G/Q, G118R, E138K, G140E/K/R/S, Y143C, S147G, Q148H/R, N155H, R263K, A49G, H51Y, Q95K, T97A, A128T, P142T, Q146L/K, E157Q, G163K/R/S, S230R, D232N] |
| Parczewski et al., 2023 [54] | Various | 57.06% of 842 (all regimens) | NR | NR | n = 3 | 3/3 (100) | NR | 1/3 (33) h [E138K, Q148R, R263K] |
| Congress Abstract | DTG Regimen | People on DTG Regimen, N | GRT Results (Historical and/or Baseline), n/N (%) | People with Baseline or Historical Mutations, n/N (%) [Mutations] | VF Outcomes, n/N (%) | |||
|
Total People
with VF |
GRT Availability
at VF |
People with Baseline Mutations and VF | People with Emergent Integrase Mutations at VF [Mutations] | |||||
| 2DR/3DR with DTG | ||||||||
| Marcelin et al., EACS 2023 [33] | DTG + 3TC, DTG + RPV, DTG/3TC/ABC | 3219 | NR | NR | 179/3219 (6) | 179/179 (100) | NR | 3/179 (2) [G140S, Q148H, E92K, N155H] |
| 3DR with DTG | ||||||||
| Bhatt et al., IAC 2023 [45] | TLD | 716 | NR | NR | 216/716 (30) | 167/216 (77) | NR | 35/167 (21) [G118R, N155H G140S/A/C/R, Q148H/R/K, Y143R/H/C, R263K] h |
| INSTI-based regimens | ||||||||
| Chieffo et al., EACS 2017 [55] | INSTI-based regimens | 40 (all regimens) | NR | EVG: 39/40 (98) b
RAL: 36/40 (90) b DTG: 8/40 (20) b [N155H/N, Q148H/Q, G140A/S, T97A, Y143C/R, E138A/K, E92Q, T66I] |
All regimens: 12/40 (30) q |
NR (assumed 100) | NR | 2/12 (17) [NR] |
| López Brull et al., GeSIDA 2019 [56] | INSTI-based regimens | 147 (all regimens) | NR | Naive (all regimens): 4/106 (4) [A128T, E157Q] |
Experienced (all regimens): 41/41 (100) e | NR (assumed 100) | NR | 6/41 (15) [G118R, R263K] c |
| Nagel et al., IDWeek 2022 [57] |
INSTI-based regimens | 1169 (all regimens) |
NR | NR | On DTG regimens: 22 All regimens: 102/1169 (9) |
On DTG regimens: 22/22 (100) | NR | All INSTI regimens: 58/102 (57) [N155H, E92Q, Q148H/R, S147G, T66I/K, E138A/K/T, G140A/S, R263K, Y143R] h,m |
| Wiesmann et al., HIV Glasgow 2022 [61] | Second-generation INSTI-based regimens | 2032 samples (all regimens) | NR | NR [On DTG regimens: K101R, V106I, V179A/I, M184V, R263K, E138A] |
All regimens: 2032/2032 (100) e | 2032/2032 (100) f | On DTG regimens: 5 r | On DTG regimens: 4 [R263K] r |
| Marom et al., EACS 2023 [34] | INSTI-based regimens | 209 (DTG-based regimens) 362 (all regimens) |
NR (assumed 100) | NR | All regimens: 72/362 (20) m | NR (assumed 100) | NR | All regimens: 25/72 (35) h,m
[R263K, Y143R, G140S, N155H, E92Q, E138K, S147G, Q148R, E157Q, T97A, V151I, L74M, S230R, Q146P s] |
| Other/Unspecified | ||||||||
| Nithianathan et al., BHIVA 2013 [58] | Unspecified | 2 | NR | NR | 1/2 (50) | 1/1 (100) | NR | 1/1 (100) [E138K, G140S, Q148H] h |
| Pulido et al., GeSIDA 2016 [59] | DTG-based regimen | 307 | NR | NR; n = 1 with resistance to RAL | 3/307 (1) | NR (at least 1) | 1/3 (33) | 1/3 (33) [NR; selective for DTG] |
| Viciana et al., HIV Glasgow 2018 [60] | Unspecified | 61 | NR | NR | 61/61 (100) e | NR (assumed 100) |
NR | 9/61 (15) [R263K, E138K, Q148H, N155H] c,h |
| Perry et al., IAC 2023 [32] | DTG- or PI-based regimen | 251 (all regimens) | NR | NR | 251/251 (100) e | INSTI region: 13/251 (5) | NR | 2/251 (1) [E138A/K, G140A, Q148R, R263K] h |
ART, antiretroviral therapy; ATV, atazanavir; BHIVA, British HIV Association; BID, twice-daily dosing; 2DR, 2-drug regimen; 3DR, 3-drug regimen; DRV, darunavir; DTG, dolutegravir; EACS, European AIDS Clinical Society; FTC, emtricitabine; GRT, genotypic resistance test; IAC, International AIDS Conference; INSTI, integrase strand transfer inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; NR, not reported; OBT, optimized background therapy; PI, protease inhibitor; PR-RT, protease–reverse transcriptase; r, ritonavir; RAL, raltegravir; RAM, resistance-associated mutation; RPV, rilpivirine; TDF, tenofovir disoproxil fumarate; TLD, tenofovir/3TC/DTG; VF, virologic failure. a Assumption; individual had no previous documented VF on DTG + FTC/TDF ART. b Only integrase resistance was evaluated. c Full results were not reported. d PR-RT; not all had integrase GRT. e All individuals had VF per analysis design. f Of the samples, 1 failed PR-RT PCR amplification. g Participants were ART-naive and/or INSTI-naive. h Whether RAMs were pre-existing or emergent could not be determined; full GRT results pre-INSTI or pre-DTG were not explicitly reported. i Only individuals with viral load ≥1000 copies/mL were analyzed; full cohort (N = 137) sequencing success rates were 99% (integrase) and 98% (PR-RT). j Authors suggest that 3 individuals had possible historical NRTI resistance. k Of the 9 individuals who developed emergent INSTI RAMs, 7 had G140 and Q148 mutations at baseline. l Only individuals who failed INSTI treatment and had emergent resistance were reported. Unknown whether RAM was emergent in 1 individual with T97A at VF. m Study did not differentiate DTG-specific data from full cohort data. n n/N represents individuals exposed to only DTG/individuals with INSTI RAMs on any regimen. o Of those studied, 5 individuals developed DTG RAMs; those listed here are RAMs described as being present in more individuals at the end of the study compared with at the start. p Viral loads >1000 copies/mL; 61/281 (22%) had successful plasma collection. q Individuals who failed to achieve virologic suppression on INSTI after starting an optimized regimen. r Here, 4 individuals receiving DTG-based regimens had unspecified historical RAMs but had INSTI RAMs at VF (R263K, n = 2; G118R, n = 2; T66I, n = 1; and E138K, n = 1). s Assumption; reported as a minor mutation of “146qr”.