Table 3. Summary of findings table.
ART with DTG compared with ART with other core agents for HIV-1 infected naive patients.
| Patient or population: treatment-naive patients with HIV infection Settings: outpatients Intervention: DTG in combination with 2 NRTI Comparison: PI (boosted DRV, ATV), or NNRTI (EFV), or INSTI (RAL, BIC) in combination with 2 NRTI | ||||||
|---|---|---|---|---|---|---|
| Outcomes | Illustrative comparative risks * (95% CI) | Relative effect: (95% CI) |
No of Participants (studies) |
Quality of the evidence (GRADE)** |
Comments | |
| Assumed risk | Corresponding risk | |||||
| CONTROLS (ALL) | DTG | |||||
| Virologic Outcomes: % pts with VL <50 cps/ml at 48 wks | ||||||
| all pts, regardless to baseline VL | 83.8% (1679/2003) | 89.2% (86.3–90.5%) | RD, 0.05 (0.03/0.08) | 4113 (7) | ⊕⊕⊕⊕ high *** | Starting treatment with DTG containing ART has an increased likelihood of achieving VL <50 cps/ml at 48 wks compared to the alternative treatments |
| baseline VL >100.000 cps/ml | 75.7% (382/504) | 83.2% (79.4–87.0%) | RD, 0.10 (0.05/0.15) | 1019 (7) | ⊕⊕⊕⊕ high | The average benefit is particularly evident in those with high baseline VL (+10%, CIs +5/+15%) |
| baseline VL <100.000 cps/ml | 86.5% (1297/1499) | 89.0% (87.3–91.7%) | RD, 0.03 (0.01/0.06) | 3094 (7) | ⊕⊕⊕⊕ high | The benefit includes also pts with low screening VL |
| INSTI (BIC, RAL) | DTG | |||||
| all pts, regardless to baseline VL | 88.4% (924/1045) | 91.0% (88.4–92.8%) | RD 0.03 (0.00/0.05) | 2096 (3) | ⊕⊕⊕⊕ high | Starting treatment with DTG containing ART has an increased likelihood of achieving VL <50 cps/ml at 48 wks compared to other INSTI |
| baseline VL >100.000 cps/ml | 80.0%(188/235) | 86.4% (80.8/91.2%) | RD 0.08 (0.01/0.14) | 453 (3) | ⊕⊕⊕⊕ high | The average benefit is particularly evident in those with high baseline VL (+8%, CIs +1/+14) |
| baseline VL <100.000 cps/ml | 90.8% (736/810) | 91.7% (89.9–94.4%) | RD 0.01 (-0.01/0.04) | 1643 (3) | ⊕⊕⊕⊝§ moderate | On average, it is unclear whether or not use of DTG compared to other INSTI increases rates of pts with undetectable VL. |
| NNRTI (EFV) | DTG | |||||
| all pts, regardless to baseline VL | 80.8% (379/469) | 86.4% (83.2–90.4%) | RD 0.07 (0.03/0.12) | 1038 (2) | ⊕⊕⊕⊕ high | starting treatment with DTG containing ART has an increased likelihood of achieving VL <50 cps/ml at 48 wks compared to EFV |
| baseline VL >100.000 cps/ml | 76.7% (109/142) | 81.3% (74.4/88.2%) | RD 0.06 (-0.03/0.15) | 247 (2) | ⊕⊕⊕⊝§ moderate | On average, it is unclear whether or not use of DTG compared to EFV increases rates of pts with undetectable VL in subgroup of pts with high baseline VL |
| baseline VL <100.000 cps/ml | 82.5% 8270/327) | 89.1 (84.9–93.2%) | RD 0.08 (0.03/0.13) | 729 (2) | ⊕⊕⊕⊕ high | starting treatment with DTG containing ART has an increased likelihood of achieving VL <50 cps/ml compared to EFV in subgroup of pts with low baseline VL |
| PI (DRV, ATV) | DTG | |||||
| all pts, regardless to baseline VL | 76.8% (376/489) | 85.2% (78.3–92.1%) | RD 0.11 (0.02/0.20) | 979 (2) | ⊕⊕⊕⊕ high | starting treatment with DTG containing ART has an increased likelihood of achieving VL <50 cps/ml at 48 wks compared to PI |
| baseline VL >100.000 cps/ml | 66.9% (85/127) | 77.2% (73.5–86.9) | RD 0.20 (0.10/0.30) | 257 (2) | ⊕⊕⊕⊕ high | The average benefit is particularly evident in those with high baseline VL (+20%, 95 CIs +10/+30) |
| baseline VL <100.000 cps/m | 80.3% (291/362) | 84.3% (78.7/89.9%) | RD 0.05 (-0.02/0.12) | 722 (2) | ⊕⊕⊕⊝§ moderate | On average, it is unclear whether or not use of DTG compared to PIs increases rates of pts with undetectable VL in subgroup of pts with low baseline VL |
| Overall rate of discontinuation of treatment in DTG recipients and controls (INSTI, PI, EFV) at 48 wks. | ||||||
| All pts. | 12.8% (257/2007) | 9.8% (7.8/11.8%) | RD -0.03 (-0.05/-0.01) | 4118 (7) | ⊕⊕⊕⊕ high | Rates of interruption of treatment for any reason (virologic failure, clinical failure, adverse events) were significantly lower in DTG recipients compared to controls |
Footnotes:
*The assumed risk is the mean control group risk of having VL <50 cps/ml at 48 wks across studies; the corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
** GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.
***Despite the fact that 3 of the included studies were judged at high risk of performance bias (open label), we judged this as high-certainty evidence because masking has limited importance for the virologic outcomes, because the risk of ascertainment bias is limited.
§ Downgraded once for imprecision (95%CI includes line of no effect)
Abbreviations: pts, patients; VL, viral load; cps, copies; wks, weeks; PI, protease inhibitors; INSTI, integrase strand transfer inhibitors; NNRTI, non-nucleoside reverse transcriptase inhibitor; NRTI, nucleoside reverse transcriptase inhibitor; EFV, efavirenz; DTG, dolutegravir; BIC, bictegravir; RAL, raltegravir; DRV, darunavir; ATV, atazanavir. CI, Confidence interval; RD, Risk Difference.