A ROBUST TRIAL vs TAF-CONTAINING REGIMENS
The TANGO trial studied virologically suppressed people living with HIV switching to DOVATO from a TAF-containing regimen through 196 weeks.
TANGO Trial Through 196 Weeks
Phase 3
randomized, multicenter, noninferiority switch study1-3
Select eligibility criteria2,3*
- Virologically suppressed adults with HIV-1 RNA <50 copies/mL for >6 months
- Stable 3- or 4-drug TAF-containing regimen: TAF/FTC + INSTI, NNRTI, or PI as initial treatment regimen
- No history of virologic failure
- No documented NRTI or INSTI resistance
- No severe hepatic impairment (Child-Pugh class C)
- HBV negative
Primary endpoint1,3
Proportion of participants with HIV-1 RNA ≥50 copies/mL at Week 48 using FDA Snapshot analysis (ITT–E) with a 4% noninferiority margin.
Secondary endpoint1,3
Proportion of participants with HIV-1 RNA ≥50 copies/mL and <50 copies/mL by Snapshot algorithm, ITT–E (4% noninferiority margin for ≥50 copies/mL and 8% noninferiority margin for <50 copies/mL) at 96 weeks and 144 weeks.
Early and Late Switch4
Patients who switched to DOVATO at Week 1 are referred to as the Early-Switch group. Patients in the TAF-containing regimens arm were switched to DOVATO at Week 148 if HIV-1 RNA <50 copies/mL (N=298) (Late-Switch group).
*Baseline third-agent-class, TAF-containing regimens included TAF/FTC plus: 79.6% INSTI ([DTG n=41; RAL n=6] n=296; EVG/c n=249); 12.9% NNRTI (n=48; RPV n=45); 7.5% PI (n=28; bDRV n=27).1,3
TANGO Baseline Characteristics1-3
DOVATO (N=369), n (%) |
TAF-Containing Regimens (N=372), n (%) |
|
|---|---|---|
| Median age (range) | 40 years (20–74) | 39 years (18–73) |
| Female | 25 (7%) | 33 (9%) |
| African American or African heritage | 50 (14%) | 58 (16%) |
| Asian | 13 (4%) | 13 (4%) |
| White | 297 (81%) | 289 (78%) |
| Hispanic or Latino | 69 (19%) | 66 (18%) |
| Median CD4+ T-cell count (range), cells/mm3 | 682 (133–1904) | 720 (119–1810) |
| CD4+ T-cell count <200 cells/mm3 | 7 (2%) | 7 (2%) |
| CDC Stage 3 (AIDS) | 20 (5%) | 19 (5%) |
| ≥1 ART stopped or switched prior to screening (any medication) | 220 (60%) | 244 (66%) |
39%
of trial participants had unknown genotypic resistance history5
Median duration of ART before Day 1 was >2.5 years3‡
‡33.8 months and 35.1 months for the DOVATO arm and TAF-containing regimens arm, respectively.
Demonstrated Noninferiority Through 144 Weeks and Durability Through 196 Weeks (4 Years)2-4,6
<1%
At Week 196, <1% of participants who switched to DOVATO from Week 1 had HIV-1 RNA ≥50 copies/mL
§The number of participants with no virologic data at Week 96 due to COVID-19 (14% for the DOVATO arm and 20% for the TAF-containing regimens arm) was a primary driver in the treatment difference in the secondary endpoint.6
A Demonstrated High Barrier to Resistance4
0
cases of treatment-emergent resistance through 4 years
in virologically suppressed adults
| Confirmed Virologic Withdrawal, n (%)2,4,6¶ | ||
|---|---|---|
DOVATO# (N=369) |
TAF-Containing Regimens# (N=372) |
|
| Week 48 | 0 | 1 (<1) |
| Week 96 | 0 | 3 (<1) |
| Week 144 | 0 | 3 (<1) |
| Week 196 | 1 (<1) | NA‖ |
39%
Including patients with unknown resistance histories, 39% of trial participants had unknown genotypic resistance history at baseline5
¶CVW was defined as HIV-1 RNA ≥50 copies/mL followed by a second consecutive HIV-1 RNA ≥200 copies/mL. Only participants meeting CVW criteria (1 for DOVATO, 3 for TCR) were evaluated for treatment-emergent resistance.2
#Of the participants in both arms, none had treatment-emergent resistance.1,2
‖Patients in the TAF-containing regimens arm were switched to DOVATO at Week 148 if HIV-1 RNA <50 copies/mL (Late Switch).4
Change From Baseline at 144 Weeks in Serum Lipids7
Prespecified Secondary Endpoint
CLINICAL SIGNIFICANCE OF THESE DATA IS UNKNOWN
**Based on TANGO trial data. Subjects on lipid-modifying agents at baseline were excluded (DOVATO: 13%; TCR: 15%). Lipid last observation carried forward data were used such that the last available fasted, on-treatment lipid value prior to the initiation of a lipid-lowering agent was used in place of future observed values.1,7
Change From Baseline at 144 Weeks in Renal Function1,8
Prespecified Secondary Endpoint††
CLINICAL SIGNIFICANCE OF THESE DATA IS UNKNOWN
††Adjusted for treatment, baseline third-agent class, baseline CD4+ T-cell count, age, sex, race, BMI, presence of diabetes, presence of hypertension, and baseline marker value.1
‡‡Based on estimated geometric means ratio of Week 144 vs baseline. Based on the same model as plasma/serum markers except adjusting for loge-transformed baseline marker.8
n=number of participants with nonmissing data at baseline and Week 144.
SEE THE IMPACT OF DOVATO IN TREATMENT-NAÏVE ADULTS
3TC=lamivudine; ART=antiretroviral therapy; bDRV=boosted darunavir; BMI=body mass index; Cl=confidence interval; CKD-EPI=Chronic Kidney Disease Epidemiology Collaboration; CVW=confirmed virologic withdrawal; DTG=dolutegravir; eGFR=estimated glomerular filtration rate; EVG/c=elvitegravir/cobicistat; ES=Early Switch; FTC=emtricitabine; HBV=hepatitis B virus; HCP=healthcare professional; HDL=high-density lipoprotein; INSTI=integrase strand transfer inhibitor; ITT–E=intent-to-treat–exposed; LDL=low-density lipoprotein; NNRTI=non-nucleoside reverse transcriptase inhibitor; NRTI=nucleoside reverse transcriptase inhibitor; PI=protease inhibitor; RAL=raltegravir; RPV=rilpivirine; SE=standard error; TAF=tenofovir alafenamide; TCR=TAF-containing regimen.
References:
1. Data on file, ViiV Healthcare.
2. Osiyemi O, De Wit S, Ajana F, et al. Efficacy and safety of switching to dolutegravir/lamivudine (DTG/3TC) versus continuing a tenofovir alafenamide-based 3- or 4-drug regimen for maintenance of virologic suppression in adults living with HIV-1: results through week 144 from the phase 3, noninferiority TANGO randomized trial. Clin Infect Dis. 2022;75(6):975-986. doi:10.1093/cid/ciac036
3. van Wyk J, Ajana F, Bisshop F, et al. Efficacy and safety of switching to dolutegravir/lamivudine fixed-dose 2-drug regimen vs continuing a tenofovir alafenamide-based 3- or 4-drug regimen for maintenance of virologic suppression in adults living with human immunodeficiency virus type 1: phase 3, randomized, noninferiority TANGO study. Clin Infect Dis. 2020;71(8):1920-1929. doi:10.1093/cid/ciz1243
4. De Wit S, Bonnet F, Osiyemi O, et al. Durable efficacy of switching from a 3-/4-drug tenofovir alafenamide (TAF)-based regimen to the 2-drug regimen dolutegravir/lamivudine (DTG/3TC) in the TANGO study through week 196. Presented at: HIV Drug Therapy Glasgow; October 23-26, 2022; Virtual and Glasgow, Scotland. Slides MO41.
5. Wang R, Wright J, Ait-Khaled M, et al. Assessing the virologic impact of archived resistance in an HIV-1 switch study TANGO through week 48. Presented at: CROI; March 8–11, 2020; Boston, MA. Poster 489.
6. van Wyk J, Ajana F, Bisshop F, et al. Switching to DTG/3TC fixed-dose combination (FDC) is non-inferior to continuing a TAF-based regimen (TBR) in maintaining virologic suppression through 96 weeks (TANGO study). Presented at: HIV Glasgow 2020; October 5-8, 2020; Virtual. Slides O441.
7. van Wyk J, Ait-Khaled M, Santos J, et al. Metabolic health outcomes at week 144 in the TANGO study, comparing a switch to DTG/3TC versus maintenance of TAF-based regimens. Presented at: 11th IAS Conference on Science; July 18-21, 2021; Virtual. Poster PEB164.
8. 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). Presented at: IDWeek™; September 29–October 3, 2021; Virtual. Poster 900.
PMUS-DLLWCNT240063 October 2024
