Of 1234 participants in the pooled TANGO and SALSA ITT-E population (DTG/3TC, n = 615; CAR, n = 619), 71% (n = 870) were aged < 50 years and 29% (n = 364) were aged ≥ 50 years (Table 1). Of note, 3% (n = 43) were aged ≥ 65 years. Overall, baseline characteristics were similar between the DTG/3TC and CAR groups. Baseline characteristics between the < 50 and ≥ 50 years age groups were generally similar across treatment groups. However, participants aged ≥ 50 years had greater concomitant medication use, more comorbidities, and longer prior ART duration compared with participants aged < 50 years. In both treatment groups, the proportions of participants with baseline non-ART medication use and comorbidities increased with age (Fig. 1). Cardiac, gastrointestinal, and metabolism disorders were the most prevalent comorbidities in participants aged ≥ 50 years. Across all participants, 131 (11%) had polypharmacy (use of > 5 medications) at baseline. The most commonly used (> 5% of the overall population) concomitant medications were cholecalciferol (9%), vitamins (not otherwise specified; 8%), and ibuprofen (6%).

Baseline A use of ≥ 1 non-ART medication and B comorbidities by age. TANGO and SALSA pooled ITT-E population. BL baseline, CAR current antiretroviral regimen, DTG dolutegravir, ITT-E intention-to-treat exposed, 3TC lamivudine

Proportions of participants with HIV-1 RNA ≥ 50 copies/mL (Snapshot, ITT-E) at Week 48 were similar among all participants regardless of age and across treatment groups (DTG/3TC vs CAR: < 50 years, < 1% [1/438] vs < 1% [2/432]; ≥ 50 years, < 1% [1/177] vs 2% [3/187]), which was consistent with results from the overall study population (DTG/3TC, < 1% [2/615]; CAR, < 1% [5/619]; Fig. 2). Notably, no participants aged ≥ 65 years had HIV-1 RNA ≥ 50 copies/mL in either treatment group. Similarly, proportions of participants with HIV-1 RNA < 50 copies/mL were high across all age and treatment groups (DTG/3TC vs CAR: < 50 years, 94% [413/438] vs 93% [402/432]; 50 to < 65 years, 91% [149/163] vs 93% [147/158]; ≥ 65 years, 100% [14/14] vs 90% [26/29]) and consistent with overall study results (DTG/3TC, 94% [576/615]; CAR, 93% [575/619]). Regardless of age category, no participants in the DTG/3TC group met CVW criteria, while 1 participant aged < 50 years in the CAR group met CVW criteria with no resistance detected.

Snapshot virologic outcomes at Week 48 overall and by age. TANGO and SALSA pooled ITT-E population. CAR current antiretroviral regimen, c/mL copies/mL, DTG dolutegravir, ITT-E intention-to-treat exposed, 3TC lamivudine

Across both age and treatment groups, adjusted mean change (SE) in CD4 + cell count from baseline to Week 48 was similar (DTG/3TC vs CAR: < 50 years, 29.0 [8.5] vs 7.6 [8.2] cells/mm3; ≥ 50 years, 6.3 [13.6] vs − 24.7 [12.5] cells/mm3), which reflected results from the overall study population (DTG/3TC, 22.4 [7.2] vs CAR, − 2.0 [6.9] cells/mm3; Additional file 1). Similar results were also observed for adjusted mean change (SE) from baseline to Week 48 in CD4 + /CD8 + ratio (DTG/3TC vs CAR: < 50 years, 0.039 [0.010] vs 0.048 [0.010]; ≥ 50 years, 0.032 [0.016] vs 0.062 [0.016]; overall, 0.037 [0.008] vs 0.052 [0.009]).

Incidence of AEs was comparable across age and treatment groups (Table 2). Adverse events leading to withdrawal and drug-related AEs were low and comparable between age groups. While serious AEs (SAEs) were generally low, more SAEs were observed in participants aged ≥ 50 years in both treatment groups (DTG/3TC vs CAR: < 50 years, 4% [18/438] vs 4% [16/432]; 50 to < 65 years, 5% [8/163] vs 8% [12/157]; ≥ 65 years, 14% [2/14] vs 14% [4/29]). In all age categories, AE incidence was comparable between the DTG/3TC and CAR groups, although drug-related AEs were more frequent in participants who switched to DTG/3TC compared with those who continued CAR (DTG/3TC vs CAR: < 50 years, 15% [65/438] vs 4% [18/432]; 50 to < 65 years, 15% [25/163] vs 2% [3/157]; ≥ 65 years, 21% [3/14] vs 0% [0/29]), which was consistent with the overall population (DTG/3TC, 15% [93/615]; CAR, 3% [21/618]).

Regardless of age category, the DTG/3TC group experienced greater weight gain from baseline at Week 48 than the CAR group, although changes in weight were small. The difference between treatment groups was not significant in participants aged < 50 years (adjusted mean change [SE] for DTG/3TC vs CAR: 1.28 [0.23] vs 1.02 [0.20] kg; treatment difference [95% CI]: 0.27 [− 0.32, 0.86]) but was significant in those aged ≥ 50 years (adjusted mean change [SE] for DTG/3TC vs CAR: 1.28 [0.36] vs 0.03 [0.30] kg; treatment difference [95% CI]: 1.24 [0.33–2.16]). These results were consistent with the overall study results (adjusted mean change [SE]: DTG/3TC, 1.28 [0.19] vs CAR, 0.71 [0.17] kg). Weight gain observed with DTG/3TC was similar between participants aged < 50 vs ≥ 50 years (1.28 kg each), while greater weight increases were observed with CAR in participants aged < 50 vs ≥ 50 years (1.02 vs 0.03 kg, respectively). Among participants aged ≥ 50 years, the difference in weight observed with DTG/3TC vs CAR was significant in female participants (adjusted mean change [SE]: 1.86 [0.61] vs − 0.21 [0.62] kg; treatment difference [95% CI]: 2.08 [0.40–3.75]) but was not significant in male participants (adjusted mean change [SE]: 0.96 [0.45] vs 0.11 [0.35] kg; treatment difference [95% CI]: 0.85 [− 0.26, 1.96]). In the overall pooled population, greater weight gain observed in the DTG/3TC group was mostly driven by outcomes from the SALSA study (adjusted mean change [SE] for DTG/3TC vs CAR: SALSA, 2.01 [0.33] vs 0.64 [0.25] kg; TANGO, 0.82 [0.23] vs 0.77 [0.22] kg; treatment difference [95% CI]: SALSA, 1.37 [0.55–2.19]; TANGO, 0.05 [− 0.57, 0.67]). Within treatment groups, the proportion of participants with ≥ 10% weight gain was low and similar across age groups (DTG/3TC vs CAR: < 50 years, 24/404 [6%] vs 17/386 [4%]; odds ratio [95% CI], 1.42 [0.75–2.73]; ≥ 50 years, 11/158 [7%] vs 5/168 [3%]; odds ratio [95% CI], 1.73 [0.59–5.60]) and consistent with the overall study results (DTG/3TC, 35/562 [6%] vs CAR, 22/554 [4%]; odds ratio [95% CI], 1.56 [0.90–2.76]; Fig. 3).

Proportion of participants with ≥ 10% weight gain at Week 48 overall and by age. TANGO and SALSA pooled safety population. CAR current antiretroviral regimen, DTG dolutegravir, 3TC lamivudine

Across both age categories, changes in lipids from baseline to Week 48 were small and generally favored DTG/3TC compared with CAR (Additional file 2). Changes from baseline to Week 48 in plasma/serum renal biomarkers were generally small in both treatment groups within each age group (Additional file 2). A greater decrease from baseline in estimated glomerular filtration rate (eGFR) based on serum cystatin C was observed in participants aged ≥ 50 years in both treatment groups compared with those aged < 50 years (adjusted mean [SE] change from baseline for DTG/3TC vs CAR: < 50 years, 0.812 [0.56] vs 0.003 [0.56] mL/min/1.73 m2; ≥ 50 years, − 3.79 [0.93] vs − 4.55 [0.89] mL/min/1.73 m2). Regardless of age category, changes in bone biomarkers from baseline to Week 48 were generally small and comparable between treatment groups (Additional file 2).