A ROBUST TRIAL vs TAF-CONTAINING REGIMENS
The TANGO trial studied suppressed PLHIV switching to DOVATO from a TAF-containing regimen through 144 weeks.
Phase 3, Randomized, Multicenter, Noninferiority Switch Study1-3
Primary Endpoint
Proportion of participants with plasma HIV-1 RNA ≥50 copies/mL (by FDA Snapshot algorithm, ITT–E, with a 4% noninferiority margin)
Secondary Endpoint
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
*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).1,4
†Once-daily DTG 50-mg/3TC 300-mg tablet.1
TANGO Baseline Characteristics1,2,4
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 HISTORY 5
MEDIAN DURATION OF ART BEFORE DAY 1 WAS >2.5 YEARS1‡
‡33.8 months and 35.1 months for the DOVATO arm and TAF-containing regimens arm, respectively.
Durable Virologic Suppression Through 144 Weeks1,2,6
Noninferior Efficacy in the ITT–E Analysis
§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 Resistance2
cases of virologic failure through 144 weeks
in virologically suppressed adults
cases of treatment-emergent resistance through 144 weeks
in virologically suppressed adults
| Confirmed Virologic Withdrawal, n (%)ǁ | ||
|---|---|---|
DOVATO (N=369) |
TAF-containing regimens¶ (N=372) |
|
| Week 48 | 0 | 1 (<1) |
| Week 96 | 0 | 3 (<1) |
| Week 144 | 0 | 3 (<1) |
INCLUDING PATIENTS WITH UNKNOWN RESISTANCE HISTORIES, 39% OF TRIAL PARTICIPANTS HAD UNKNOWN GENOTYPIC RESISTANCE HISTORY AT BASELINE 5
ǁCVW 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 were evaluated for treatment-emergent resistance. Because no participant in the DOVATO arm met CVW criteria, none were evaluated for treatment-emergent resistance.1,6
¶Of the participants in the TAF-containing regimens arm, none had treatment-emergent resistance.1,6
Change From Baseline at 144 Weeks in Serum Lipids7
Prespecified Secondary Endpoint
#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.4,7
CLINICAL SIGNIFICANCE OF THESE DATA IS UNKNOWN
Change From Baseline at 144 Weeks in Renal Function4,8
Prespecified Secondary Endpoint**
**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.
††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.
n=number of participants with nonmissing data at baseline and Week 144.
CLINICAL SIGNIFICANCE OF THESE DATA IS UNKNOWN
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; FTC=emtricitabine; HBV=hepatitis B virus; 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; PLHIV=people living with HIV; RAL=raltegravir; RPV=rilpivirine; SE=standard error; TAF=tenofovir alafenamide; TCR=TAF-containing regimen.
References:
1. 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
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, non-inferiority TANGO randomized trial. Clin Infect Dis. 2022;75(6):975-986. doi:10.1093/cid/ciac036
3. 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, non-inferiority TANGO randomized trial. Clin Infect Dis. 2022;75(6)(suppl):1-18. doi:10.1093/cid/ciac036
4. Data on file, ViiV Healthcare.
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.
DLLWCNT230004 July 2023
