Table 2.
Summary of trials comparing two-drug regimens as maintenance/switch treatment in people living with HIV-1
| Title | Study agents | Study design | Outcomes | Emergent resistance | Additional comments |
|---|---|---|---|---|---|
| NRTI-inclusive regimens | |||||
| TANGO [27] | DTG + 3TC (n = 369) | Phase 3, open-label, randomized non-inferior, switch study performed in the USA, Spain, UK, The Netherlands, Germany, Japan, France, Canada, Belgium, Australia | VL < 50 copies/ml at W48 (ITT): | TAF-based regimen: 0/1 | Non-inferiority met |
| TAF-containing 3 or 4DR (n = 372) | |||||
| 2DR: 93% | |||||
| 3 or 4DR: 93% | |||||
| ASPIRE [28] | DTG + 3TC (n = 45) | Open-label, randomized, non-inferiority study performed in the USA | VL < 50 copies/ml at W48 (ITT): | 2DR group: 0/1 | Non-inferiority met |
| Continue 3DR (n = 45) | |||||
| 2DR: 91% | |||||
| 3DR: 89% | |||||
| ATLAS-M [29] | ATV/r + 3TC (n = 133) | Open-label, randomized, non-inferiority study performed in Italy | VL < 50 copies/ml at W48 (ITT): | 2DR group: 0/2 | Non-inferiority met |
| Superiority identified in post hoc analysis for 2DR group | |||||
| Continue ATV/r + 2 NRTIs (n = 133) | 3DR group: 0/6 | ||||
| 2DR: 90% | |||||
| 3DR: 80% | |||||
| DUAL GESIDA [30] | DRV/r + 3TC (n = 129) | Phase 4, open-label, randomized, non-inferiority study performed in Spain | VL < 50 copies/ml W48 (ITT): | 2DR group: 0/4 | Non-inferiority met |
| DRV/r + 2NRTIs (n = 128) | 3DR group: 0/2 | ||||
| 2DR: 89% | |||||
| 3DR: 93% | |||||
| OLE [31] | LPV/r + 3TC (n = 123) | Open-label, randomized, non-inferiority trial performed in Spain and France | VL < 50 copies/ml at W48 (ITT): | 2DR group: 0/3* | Non-inferiority met |
| *One case of NRTI resistance in 2DR group found to be a previously archived mutation | |||||
| LPV/r + 2NRTIs (n = 127) | 3DR group: 0/3 | ||||
| 2DR: 88% | |||||
| 3DR: 87% | |||||
| SALT [32] | ATV/r + 3TC (n = 143) | Open-label, randomized, non-inferiority study performed in Spain | VL < 50 copies/ml at W48 (ITT): | 2DR group: 0/6 | Non-inferiority met |
| ATV/r + 2NRTIs (n = 143) | 3DR group: 1/4 | ||||
| 2DR: 77% | |||||
| 3DR: 76% | |||||
| NRTI: 1 | |||||
| SALT (96 weeks) [33] | VL < 50 copies/ml at W96 (ITT): | 2DR group: 0/9 | Non-inferiority met | ||
| 3DR group: 1/5 | |||||
| 2DR: 74% | |||||
| 3DR: 74% | NRTI: 1 | ||||
| COOL [34] | EFV + TDF (n = 74) | Open-label, randomized, non-inferiority study performed in France | VL < 50 copies/ml at W48 (ITT): | 2DR group: 3/3 | 2DR failed to meet non-inferiority |
| EFV + TDF + 3TC (n = 74) | NNRTI: 3 | ||||
| 2DR: 82% | |||||
| 3DR: 97% | |||||
| NRTI-sparing regimens | |||||
| DUALIS [35] | DTG + DRV/r (n = 131) | Phase 3b, open-label, randomized, non-inferiority, switch study performed in Germany | VL < 50 copies/ml at W48 (ITT): | Not reported but no treatment emergent resistance | Non-inferiority met |
| Continue 3DR (n = 132) | Premature termination of recruitment due to slow recruitment | ||||
| DTG + DRV/r: 86% | |||||
| Continued 3DR: 88% | |||||
| SWORD 1/SWORD 2 [36] | SWORD-1 | Phase 3, open-label, parallel-group, randomized, non-inferiority switch study performed in 12 countries | VL < 50 copies/ml at W48 (ITT): | 2DR group: 1/3 | Non-inferiority met |
| DTG/RPV (n = 252) | |||||
| NNRTI: 1 | |||||
| Current 3DR (n = 256) | SWORD-1 | 3DR group: 0/6 | |||
| 2DR: 95% | |||||
| SWORD-2 | 3DR: 96% | ||||
| DTG/RPV (n = 261) | SWORD-2 | ||||
| 2DR: 94% | |||||
| Current 3DR (n = 255) | 3DR: 94% | ||||
| SWORD 1/SWORD 2 148-Week Open-Label Extension Data [37] | Early switch-original SWORD 1/SWORD 2 DTG/RPV cohort | Phase 3, OLE performed in 12 countries | VL < 50 copies/ml at W148 (ITT): | Early switch: 4/14 | Non-inferiority met |
| NNRTI: 4 | |||||
| Early switch: 84% | Late switch: 2/11 | ||||
| Late switch-3DR patients virologically suppressed at W48 switched to DTG/RPV at W52 | |||||
| Late switch: 90% | NNRTI: 2 | ||||
| DTG/RPV early switch (n = 513) | |||||
| DTG/RPV late switch (n = 477) | |||||
| ATLAS [38] | 4-week induction for IM CAB/RPV group: oral CAB 25 mg + RPV 25 mg | Open-label, randomized, non-inferiority, switch study performed in the USA, Italy, Germany, Spain, South Africa, Russia, Canada, and Belgium | VL < 50 copies/ml at W48 (ITT): | 2DR group: 3/3 | Non-inferiority met |
| Patient satisfaction survey reported 97% of patients were more satisfied with IM regimen over oral regimen during lead-in phase | |||||
| NNRTI: 3 | |||||
| INSTI: 1 | |||||
| IM CAB/RPV: 93% | 3DR group: 3/4 | ||||
| 3DR: 96% | |||||
| LA CAB/RPV (400/600 mg) every 4 weeks (n = 308) | NRTI: 2 | ||||
| NNRTI: 2 | |||||
| NNRTI/PI/INSTI + 2 NRTIs (n = 308) | |||||
| PROBE [39] | DRV/r + RPV (n = 30) | Open-label, randomized, non-inferiority, switch study performed in Italy | VL < 50 copies/ml at W48 (ITT): | None in either group | Non-inferiority met |
| Continue 3DR (n = 30) | 3DR limited to ATV or DRV/r + 2NRTIs (most common NRTI-backbone TDF/FTC) | ||||
| 2DR: 97% | |||||
| 3DR: 93% | |||||
| MARCH [40] | MVC + PI/r (n = 158) | Open-label, randomized, non-inferiority, switch study performed in various countries | VL < 50 copies/ml at W48 (ITT): | MVC + PI/r: 4/18 | Switch to NRTI-sparing 2DR found to be inferior and was discontinued from the complete 96-week study period |
| NNRTI: 1 | |||||
| MCV + PI/r: 78% | |||||
| PI: 1 | |||||
| MVC + 2NRTIs: 92% | |||||
| MVC + 2NRTIs (n = 157) | CXCR4 tropic: 3 | ||||
| Continued 3DR: 95% | |||||
| MVC + 2NRTIs: 5/6 | |||||
| Continue 3DR (n = 82) | |||||
| NNRTI: 2 | |||||
| NRTI: 5 | |||||
| PI: 1 | |||||
| Continued 3DR: 1/1 | |||||
| NNRTI: 1 | |||||
| HARNESS [41] | ATV/r + RAL (n = 72) | Open-label randomized, pilot switch study performed in the USA, UK, Germany, Spain, Italy, France, and Poland | VL < 50 copies/ml at W48 (ITT): | 2DR group: 2/9 | Study terminated due to increased virologic rebound and emergent resistance in 2DR |
| ATV/r + TDF/3TC (n = 37) | |||||
| 2DR: 69% | |||||
| 3DR: 87% | PI: 1 | ||||
| INSTI: 2 | |||||
| 3DR group: 0/1 | |||||
| SECOND-LINE [42] | LPV/r + RAL (n = 270) | Phase 3b/4, randomized, open-label, non-inferiority study performed in Africa, Asia, Europe, and Latin America | VL < 50 copies/ml at W96 (ITT): | 2DR group: 23/83 | Non-inferiority met |
| LPV/r + 2 NRTIs (n = 271) | NRTI: 2 | Limited to treatment-experienced patients with evidence of virologic failure on NNRTI + dual NRTI regimen | |||
| 2DR: 70% | PI: 1 | ||||
| 3DR: 68% | INSTI: 20 | ||||
| 3DR group: 11/82 | |||||
| NRTI: 8 | |||||
| PI: 2 | |||||
| INSTI: 1 | |||||
| KITE [43] | LPV/r + RAL (n = 40) | Open-label, randomized, pilot switch study performed in Atlanta, GA, USA | VL < 50 copies/ml at W48 (ITT): | 2DR group: */1 | *Treatment-emergent resistance among cases of virologic failure not assessed |
| Current 3DR (n = 20) | 3DR group: */2 | ||||
| 2DR: 92% | |||||
| 3DR: 88% | |||||
2DR two-drug regimen, 3DR three-drug regimen, 3TC lamivudine, ABC abacavir, ATV/r ritonavir-boosted atazanavir, AZT zidovudine, CAB cabotegravir, DRV/r ritonavir-boosted darunavir, DTG dolutegravir, EFV efavirenz, FAS full analysis set, FTC emtricitabine, INSTI integrase strand transfer inhibitors, ITT intention to treat, LA long acting, LPV/r ritonavir boosted lopinavir, mITT modified intent to treat, MVC maraviroc, NRTI nucleoside reverse transcriptase inhibitor, NNRTI non- nucleoside reverse transcriptase inhibitors, PI protease inhibitor, OLE open-label extension, RAL raltegravir, RAM resistance associated mutations, RCT randomized controlled trial, RPV rilpivirine, TDF tenofovir disoproxil fumarate, VL viral load, W48 week 48, W96 week 96, W148 week 148