TANGO is a randomized open-label study in which subjects with virologic suppression on standard 3-drug TAF-based ART either switched to the 2-drug regimen of dolutegravir (DTG)/lamivudine (3TC) n = 369) or continued their baseline ART (n = 372). Previously published data showed no significant difference between the regimens in viral suppression at 48 weeks. At the recent International AIDS Society and IDWeek meetings, researchers presented week 144 data on efficacy, safety, and select metabolic outcomes.
The TANGO study population was >90% male, 80% white, and the median age was 40 years; 78% were on an INSTI at baseline (66% were on elvitegravir/cobicistat), and 74% were on a pharmacokinetic (PK) booster (in combination with elvitegravir or a PI). Subjects had been on ART a median of 34 months, and on TAF for a median of 18 months. At baseline, the groups had roughly similar metabolic parameters and BMI.
Key findings of the study are that at week 144:
- Viral suppression to <50 copies/mL was maintained in 85.9% of the DTG/3TC group and 81.7% of the group who continued their baseline ART, again meeting criteria for noninferiority of the 2-drug regimen (1/369 in the 2-drug group and 5/372 in the 3-drug group had HIV RNA ≥50).
- Median weight gain was slightly greater in the DTG/3TC switch group (+2.2 kg) than in the continued TAF-based ART group (+1.7 kg); these differences were not statistically significant. Weight gain was seen regardless of baseline weight category (underweight, overweight, obese), and there were no differences between treatment groups in proportions who gained >5% or >10% from baseline.
- Changes (not stated whether median or mean) in fasting lipids through 144 weeks were not substantial in either group – in the DTG/3TC group, total cholesterol, LDL, and HDL decreased 2.4-3.3% while triglycerides levels decreased 9.7%; in the TAF-based ART group, all lipid fractions increased somewhat (2.2-4.6%). However, total cholesterol/HDL ratios were virtually unchanged from baseline and the difference between groups was not significant.
- Glucose levels were essentially unchanged from baseline in both groups at week 144, and increases in the rates of insulin resistance (11%) and metabolic syndrome (15-16%) were the same in the two groups.
- There were minimal (and not significantly different) changes in select inflammatory markers in the two groups.
Clinical bottom line
Compared with continuing standard 3-drug TAF-based ART, over 3 years of follow-up, a switch from 3-drug TAF-based ART to DTG/3TC maintained HIV viral suppression but did not result in better outcomes with regard to weight gain, total cholesterol/HDL, glucose metabolism, or markers of inflammation.
SALSA is similar to a randomized open-label study in which subjects with virologic suppression on standard 3-drug ART either switched to the 2-drug regimen of DTG/lamivudine (3TC) (n = 246) or continued their baseline ART (n = 247). Unlike the TANGO study (see above), which included only patients on TAF-based regimens at baseline, SALSA included subjects on any regimen containing 2 NRTIs + an INSTI, NNRTI, or PI. Subjects had no history of virologic failure and no known resistance to NRTIs or INSTIs.
Researchers presented week 48 data on virologic efficacy and metabolic outcomes at the 2021 International AIDS Society conference. At baseline, the two treatment groups were well matched for most characteristics; in the DTG/3TC arm 44% were women, 61% were white, 18% were African American or of African heritage, and median BMI was 25. 40% were taking an INSTI, 50% an NNRTI, 10% a PI; 44% were on TDF and 34% were on TAF.
At 48 weeks, viral suppression to <50 copies/mL was maintained in 94% of the DTG/3TC group and 93% of those who continued their baseline regimen; these results met criteria for noninferiority of DTG/3TC. Only one participant in each study arm had a viral load >40 copies/mL (these were between 50 and 70 c/mL); 14% in each group had no data at week 48.
Evaluation of select metabolic parameters and biomarkers of renal and bone health showed that:
- Mean weight changes were +2.1 kg in the DTG/3TC group and +0.6 kg in the 3-drug group.
- Lipids: changes from baseline in total cholesterol, LDL, and triglycerides were small and similar in both groups; the total cholesterol/HDL ratio increased slightly more in the DTG/3TC group (1.8% vs 0.2%). No information was given on what proportion in each group started lipid-lowering therapy.
- Changes in renal function as measured by eGFR based on cystatin C measurements were slight and nearly equivalent in the two groups (-1.5 and -0.9 mL/min/1.73m2 in the DTG/3TC and 3-drug groups respectively), while decreases in eGFR as based on creatinine (Cr) measures were greater in the DTG/3TC group (owing to greater increases in Cr in this group).
- Urine protein/Cr ratio decreased 27% in those on DTG/3TC and 9.6% of those in the 3-drug group, and other markers of proximal tubule function, were better in the DTG/3TC group.
- Three (out of four) markers of bone turnover improved somewhat in the DTG/3TC group.
Clinical bottom line
In appropriately chosen individuals, a switch from standard 3-drug ART to the 2-drug regimen of DTG/3TC maintained viral suppression and resulted in little change in lipid, renal, or bone parameters at 48 weeks. The switch, did, however, result in more weight gain in persons on the 2-drug regimen. Presenters gave no breakdown of weight gain according to baseline ARVs (or demographic factors), so it is unclear what specific ARV changes (e.g., whether removal of TDF or addition of DTG) were associated with weight changes.
- Jean van Wyk, Mounir Ait-Khaled, Jesus Santos, et al. Metabolic Health Outcomes At Week 144 in the TANGO Study, Comparing a Switch to DTG/3TC versus Maintenance of TAF-Based Regimen. 11th IAS Conference on HIV Science, July 18-21, 2021. Abstract PEB164.
- Osiyemi O, Ajana F, Bisshop F, et al. Switching to DTG/3TC fixed-dose combination (FDC) is non-inferior to continuing a TAF-based regimen in maintaining virologic suppression through 144 weeks (TANGO Study). IDWeek, September 29-October 3, 2021. Abstract 900.
- Llibre JM, Brites CA, Cheng C-Y, et al. Switching to the 2-Drug Regimen of Dolutegravir/Lamivudine (DTG/3TC) Fixed-Dose Combination is Non-Inferior to Continuing a 3-Drug Regimen through 48 Weeks in a Randomized Clinical Trial (SALSA). 11th IAS Conference on HIV Science July 18-21, 2021. Abstract OALB0303.