STUDIED >1400 TREATMENT-NAÏVE ADULTS THROUGH 144 WEEKS
GEMINI 1 & 2: Studied >1400 Treatment-Naïve Adults Through 144 Weeks1,2
GEMINI 1 & 2 (pooled): Phase 3, Identically Designed, Double-Blind, Noninferiority Trials
Primary Endpoint
Proportion of participants with HIV-1 RNA <50 copies/mL at Week 48 (by FDA Snapshot algorithm, ITT–E with a 10% noninferiority margin)
Secondary Endpoint
Proportion of participants with plasma HIV-1 RNA <50 copies/mL at Weeks 96 and 144 (by FDA Snapshot algorithm for the ITT–E with a 10% noninferiority margin)
GEMINI Baseline Characteristics (Pooled)1
DOVATO (N=716), n (%) |
DTG + TDF/FTC (N =717), n (%) |
|
|---|---|---|
| Median age | 32 years | 33 years |
| Female | 113 (16%) | 98 (14%) |
| African American or African heritage | 99 (14%) | 76 (11%) |
| White | 480 (67%) | 497 (69%) |
| Asian | 71 (10%) | 72 (10%) |
HIV-1 RNA >100,000 copies/mL* |
140 (20%) | 153 (21%) |
| CD4+ T-cell count ≤200 cells/mm3 | 63 (9%) | 55 (8%) |
| CDC Stage 3 (AIDS) | 66 (9%) | 60 (8%) |
| HCV co-infection | 39 (5%) | 49 (7%) |
20% OF PARTICIPANTS ON DOVATO HAD BASELINE VIRAL LOADS >100,000 COPIES/mL
*2% of participants in each arm had baseline HIV-1 RNA ≥500,000 copies/mL.
Proven, Sustained Virologic Suppression Through 144 Weeks1,3,4
GEMINI 1 & 2—DOVATO Was Noninferior to DTG + TDF/FTC at 48, 96, and 144 Weeks
Pooled Virologic Response (ITT–E; Snapshot analysis)
The evaluation of antiviral activity over time was a prespecified secondary endpoint, ITT–E population.
DOVATO VIROLOGIC SUPPRESSION
•RAPID: 72% at Week 4 •POWERFUL: 91% at Week 48 •DURABLE: 82% at Week 144
Post Hoc Analysis: Participants With HIV-1 RNA <50 copies/mL at Week 144, by Adherence Category5†
Participants were stratified by ≥90% vs <90% adherence
Methods
- Association between adherence and virologic suppression was evaluated at Week 144 using FDA Snapshot
- Adherence (%) was calculated as the number of pills taken (pills returned subtracted from pills available) per number of pills prescribed, estimated using pill count data
FDA Snapshot Treatment Difference
- ≥90% adherence: –2.6% (95% CI; –7.9%, 2.7%); <90% adherence: 1.8% (95% CI; –21.5%, 25.9%)
Limitations
- Small number of participants in the lower adherence subgroup (5% in both arms)
- Utilizing pill count to accurately measure adherence
- Increase in number of patients with no virologic data since Week 48 due to COVID-19
†Results from post hoc analysis are descriptive only.
High Barrier to Resistance Through 144 Weeks in Treatment-Naïve Adults3
CVW‡ (cumulative) |
All Partipants With Treatment-Emergent Mutations |
|
|---|---|---|
DOVATO (N=716) |
12 | 1§ |
DTG + TDF/FTC (N=716) |
9 |
0 |
‡CVW—defined as either virologic nonresponse (a decrease in plasma HIV-1 RNA of <1 log10 copies/mL by Week 12, with subsequent confirmation, unless plasma HIV-1 RNA is <200 copies/mL or confirmed plasma HIV-1 RNA ≥200 copies/mL on or after Week 24) or virologic rebound (confirmed rebound in plasma HIV-1 RNA levels to ≥200 copies/mL after prior confirmed suppression to <200 copies/mL).1
§1/716 in the DOVATO arm developed treatment-emergent resistance (M184V at Week 132 and R263R/K at Week 144). In the DTG + TDF/FTC arm, there were no resistance mutations observed among participants.3
In 12 Cases of Confirmed Virologic Withdrawal, Viral Rebound Did Not Lead to Resistance2
participants had treatment-emergent INSTI or NRTI substitutions conferring resistance through 144 weeks
EXPLORE THE PERFORMANCE OF DOVATO IN A TEST-AND-TREAT SETTING
Cl=confidence interval; CrCl=creatinine clearance; CVW=confirmed virologic withdrawal; DTG=dolutegravir; FTC=emtricitabine; HBV=hepatitis B virus; HCV=hepatitis C virus; INSTI=integrase strand transfer inhibitor; ITT–E=intent-to-treat–exposed; NRTI=nucleoside reverse transcriptase inhibitor; TDF=tenofovir disoproxil fumarate.
References:
1. Cahn P, Madero JS, Arribas JR, et al; GEMINI Study Team. Dolutegravir plus lamivudine versus dolutegravir plus tenofovir disoproxil fumarate and emtricitabine in antiretroviral-naive adults with HIV-1 infection (GEMINI-1 and GEMINI-2): week 48 results from two multicentre, double-blind, randomised, non-inferiority, phase 3 trials. Lancet. 2019;393(10167):143-155. doi:10.1016/S0140-6736(18)32462-0
2. Data on file, ViiV Healthcare.
3. Cahn P, Madero JS, Arribas JR, et al. Three-year durable efficacy of dolutegravir plus lamivudine in antiretroviral therapy-naïve adults with HIV-1 infection. AIDS. 2022;36(1):39-48. doi:10.1097/QAD.0000000000003070
4. Cahn P, Madero JS, Arribas JR, et al. Durable efficacy of dolutegravir plus lamivudine in antiretroviral treatment-naïve adults with HIV-1 infection: 96-week results from the GEMINI-1 and GEMINI-2 randomized clinical trials. J Acquir Immune Defic Syndr. 2020;83(3):310-318. doi:10.1097/QAI.0000000000002275
5. Fernvik E, Madero JS, Espinosa N, et al. Impact of treatment adherence on efficacy of DTG + 3TC and DTG + TDF/FTC: pooled week 144 analysis of the GEMINI-1 and GEMINI-2 clinical studies. Presented at: 18th European AIDS Conference; October 27–30, 2021; Virtual. Poster PE2/63.
DLLWCNT230005 July 2023
