Table 2.
Emergent INSTI-associated drug resistance mutations (DRMs) in INSTI-naive persons with active virus replication receiving a standard dolutegravir (DTG)-containing regimen
| AuthorYr | Population | Past ART | DTG ART (q24h) | Subjects | Subjects with DRMs | Emergent INSTI DRMsa |
|---|---|---|---|---|---|---|
| Underwood15 | RCT (SAILING) | ART experienced; INSTI naive; resistance to ≥2 classes but with 1 or 2 fully active drugs for OB | DTG/OB × 48W (Phase I); post 48W (Phase II) | 354 | 5 | (1) R263K |
| (2) R263K | ||||||
| (3) T97A, N155H (C) | ||||||
| (4) N155H (A) | ||||||
| (5) A49G, S230R, R263K | ||||||
| Vavro18 | trial (P1093) | ART experienced; INSTI naive | DTG/OB | 61 | 3 | (1) A49G, M50V, E138T, S147G, R263K |
| (2) L74M, G118R | ||||||
| (3) G118R | ||||||
| Taiwo18 | trial (A5353) | ART naive | DTG/3TC | 120 | 1 | (1) R263K |
| Wang18 | RCT (DAWNING) | ART experienced; INSTI naive; h/o VF on first-line ART | DTG + 2 NRTIs (48W) | 297 | 2 | (1) H51Y, G118R, E138K, R263K |
| (2) G118R | ||||||
| Lepik17 | cohort | INSTI naive | DTG + 2 NRTIs | 310 | 3 | (1) R263K |
| (2) R263K | ||||||
| (3) T66I | ||||||
| Ahmed19 | case report | ART experienced; INSTI naive | DTG/OB | 1 | 1 | (1) R263K (D) |
| Fulcher18 | case report | ART naive | DTG/TDF/FTC | 1 | 1 | (1) Q148K, G163E |
| Pena Lopez18b | case report | ART naive | DTG/TDF/FTC | 1 | 1 | (1) E157Q, R263K (CRF14_BG) |
| Seatla18 | case report | ART experienced; INSTI naive | DTG/OB | 1 | 1 | (1) G118R, E138K |
| Cardoso18 | case report | ART experienced; INSTI naive | DTG + 2 NRTIs | 2 | 2 | (1) E157Q, R263K |
| (2) R263K (G) | ||||||
| Lubke18 | case report | ART naive | DTG/TDF/FTC | 1 | 1 | (1) G118R, R263K (F) |
RCT, randomized clinical trial; OB, optimized background; W, weeks; h/o, history of.
Subtypes are indicated in parentheses.
DTG was administered twice daily in a person who was also receiving rifampicin in Pena Lopez18. In Underwood15, the two cases of R263K were reported in the first 48 weeks of the SAILING trial.15 The three additional cases of INSTI DRMs in this trial occurred between weeks 72 and 120. In Wang18,17 the first isolate contained 3 clones with H51Y/G118R and 11 clones with G118R/E138K/R263K. In Lepik17, R263K was detected in two ART-experienced persons and T66I in a previously ART-naive person. Complete sequences were unavailable for all isolates in this table.