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a −10% non-inferiority margin for individual studies. PowerPoint Presentation
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a −10% non-inferiority margin for individual studies.

a −10% non-inferiority margin for individual studies.

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a −10% non-inferiority margin for individual studies.

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  1. DURABLE EFFICACY OF DOLUTEGRAVIR (DTG) PLUS LAMIVUDINE (3TC) IN ANTIRETROVIRAL TREATMENT–NAIVE ADULTS WITH HIV-1 INFECTION: 96-WEEK RESULTS FROM THE GEMINI STUDIES 1Fundación Huesped, Buenos Aires, Argentina; 2Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico; 3Hospital La Paz, Madrid, Spain; 4Istituto Nazionale per le Malattie Infettive Lazzaro Spallanzani, Rome, Italy; 5Bliss Healthcare Services, Orlando, FL, USA; 6Royal Sussex County Hospital, Brighton, UK; 7Brighton & Sussex Medical School, Brighton, UK; 8National Taiwan University Hospital, Taipei, Taiwan; 9Rheinische Friedrich-Wilhelms Universität, Bonn, Germany; 10Hôpital Saint Antoine, Paris, France; 11ViiV Healthcare, Brentford, UK; 12ViiV Healthcare, Research Triangle Park, NC, USA; 13GlaxoSmithKline, Stockley Park, UK P Cahn,1 J Sierra Madero,2 J Arribas,3 A Antinori,4 R Ortiz,5 A Clarke,6,7 C-C Hung,8J Rockstroh,9 P-M Girard,10 J Sievers,11 C Man,12 R Urbaityte,13 M Underwood,12A Tenorio,12 K Pappa,12 B Wynne,12 M Gartland,12 M Aboud,11 J van Wyk,11 KY Smith12

  2. Identically designed, randomized, double-blind, parallel-group, multicenter, non-inferiority studies 1:1 • ART-naive adults Screening (28 days) Double-blind phase Open-labelphase Continuation phase DTG + 3TC (N=716) DTG + 3TC DTG + TDF/FTC(N=717) Day 1 Week 24 Week48 Week96 Week144 Eligibility criteria • VL 1000-500,000 c/mL at screening • ≤10 days of prior ART • No major RT or PI resistance mutation • No HBV infection or need for HCV therapy CountriesArgentina Australia Belgium Canada France Germany Italy Republic of Korea Mexico Netherlands Peru PolandPortugal Romania Russian Federation South AfricaSpain Switzerland TaiwanUnited Kingdom United States Primary endpoint at Week 48: participants withHIV-1 RNA <50 c/mL (ITT-E Snapshot)a Baseline stratification factors: plasma HIV-1 RNA (≤100,000 vs >100,000 c/mL) and CD4+ cell count (≤200 vs >200 cells/mm3). a−10% non-inferiority margin for individual studies. Cahn et al. IAS 2019; Mexico City, Mexico. Slides WEAB0404LB. GEMINI-1 AND GEMINI-2 PHASE III STUDY DESIGN Download Slides: Bit.ly/gemini96wk

  3. a2% of participants in each group had baseline HIV-1 RNA >500,000 c/mL and were included in the ITT-E analysis. Cahn et al. Lancet. 2019;393:143-155. Cahn et al. IAS 2019; Mexico City, Mexico. Slides WEAB0404LB. DEMOGRAPHIC AND BASELINE CHARACTERISTICS FOR THE POOLED GEMINI-1 AND GEMINI-2 POPULATION Download Slides: Bit.ly/gemini96wk

  4. Snapshot Snapshot 0 4 8 12 16 24 36 48 60 72 84 96 Non-inferiority criteria were met for GEMINI-1, GEMINI-2, and the pooled analysisb aBased on Cochran-Mantel-Haenszel stratified analysis adjusting for the following baseline stratification factors: plasma HIV-1 RNA (≤100,000 vs >100,000 c/mL),CD4+ cell count (≤200 vs >200 cells/mm3), and study (GEMINI-1 vs GEMINI-2). The upper limit of the 95% CI for the pooled analysis was 0.0007%. bIn GEMINI-1, HIV-1 RNA <50 c/mL (95% CI) was achieved in 300/356 participants (84.3% [80.5-88.1]) in the DTG+ 3TC group and 320/358 (89.4% [86.2-92.6]) in the DTG + TDF/FTC group (adjusted treatment difference [95% CI], −4.9% [−9.8, 0.03]). In GEMINI-2, the corresponding values were 316/360 (87.8% [84.4-91.2]) and 322/359 (89.7% [86.5-92.8]), respectively (adjusted treatment difference [95% CI], −1.8% [−6.4, 2.7]). Cahn et al. IAS 2019; Mexico City, Mexico. Slides WEAB0404LB. DTG + 3TC IS NON-INFERIOR TO DTG + TDF/FTC IN SNAPSHOT HIV-1 RNA <50 C/ML AT WEEK 96 Download Slides: Bit.ly/gemini96wk

  5. Snapshot Snapshot TRDF 0 4 8 12 16 24 36 48 60 72 84 96 Non-inferiority criteria were met for GEMINI-1, GEMINI-2, and the pooled analysis Treatment related discontinuation = failure (TRDF) population accounts for confirmed virologic withdrawal, withdrawal due to lack of efficacy, withdrawal due to treatment-related AE, and participants who met protocol-defined stopping criteria aBased on Cochran-Mantel-Haenszel stratified analysis adjusting for the following baseline stratification factors: plasma HIV-1 RNA (≤100,000 vs >100,000 c/mL), CD4+ cell count (≤200 vs >200 cells/mm3), and study (GEMINI-1 vs GEMINI-2). The upper limit of the 95% CI for the pooled analysis was 0.0007%. TRDF (unadjusted difference) was a pre-planned analysis at Week 96. bIn GEMINI-1, HIV-1 RNA <50 c/mL (95% CI) was achieved in 300/356 participants (84.3% [80.5-88.1]) in the DTG + 3TC group and 320/358 (89.4% [86.2-92.6]) in the DTG + TDF/FTC group (adjusted treatment difference [95% CI], −4.9% [−9.8, 0.03]). In GEMINI-2, the corresponding values were 316/360 (87.8% [84.4-91.2]) and 322/359 (89.7% [86.5-92.8]), respectively (adjusted treatment difference [95% CI], −1.8% [−6.4, 2.7]). Cahn et al. IAS 2019; Mexico City, Mexico. Slides WEAB0404LB. DTG + 3TC IS NON-INFERIOR TO DTG + TDF/FTC IN SNAPSHOT HIV-1 RNA <50 C/ML AT WEEK 96 Download Slides: Bit.ly/gemini96wk

  6. aOne participant met the criteria for CVW at Week 12 but was not reported at the Week 48 analysis because of a laboratory reporting error identified after the Week 48 analysis. Cahn et al. IAS 2019; Mexico City, Mexico. Slides WEAB0404LB. NO TREATMENT-EMERGENT RESISTANCE WAS OBSERVED AMONG PARTICIPANTS WHO MET CONFIRMED VIROLOGIC WITHDRAWAL CRITERIA Download Slides: Bit.ly/gemini96wk

  7. Virologic outcomes Summary of no virologic data at Snapshot aIn participants with no virologic data at Week 96, none had last HIV-1 RNA value >50 c/mL except for 1 participant in the DTG +TDF/FTC group. bOther reasons for discontinuation at Week 96 included protocol deviation, lost to follow-up, physician decision, withdrawal by participant, and lack of efficacy (in 1 participant in the DTG + TDF/FTC group). Cahn et al. Lancet. 2019;393:143-155. Cahn et al. IAS 2019; Mexico City, Mexico. Slides WEAB0404LB. PROPORTION OF PARTICIPANTS WITH SNAPSHOT HIV-1 RNA ≥50 C/ML SIMILAR FROM WEEK 48 TO WEEK 96 IN BOTH GROUPS Download Slides: Bit.ly/gemini96wk

  8. TRDFaDTG + 3TCDTG + TDF/FTC SnapshotDTG + 3TCDTG + TDF/FTC HIV-1 RNA <50 c/mL or without TRDF, % 499/ 576 510/ 564 560/ 576 545/ 564 117/ 140 132/ 153 132/ 140 146/ 153 573/ 653 594/ 662 633/ 653 638/ 662 43/ 63 48/ 55 59/ 63 53/55 n/N >200 ≤200 ≤100,000 >100,000 Baseline CD4+ cell count, cells/mm3 Baseline HIV-1 RNA, c/mL At Week 96, there were 3 confirmed virologic withdrawals in the DTG + 3TC group and 2 in the DTG + TDF/FTC group in the CD4 < 200 stratum TRDF, treatment-related discontinuation equals failure. aTRDF was a pre-planned analysis at Week 96. Cahn et al. IAS 2019; Mexico City, Mexico. Slides WEAB0404LB. PROPORTION OF PARTICIPANTS WITH HIV-1 RNA <50 C/ML BY BASELINE VIRAL LOAD AND CD4+ CELL COUNT AT WEEK 96: SNAPSHOT AND TRDF ANALYSIS Download Slides: Bit.ly/gemini96wk

  9. Increased weight was reported as an AE in 13 (1.8%) participants treated with DTG + 3TC and in 10 (1.4%) treated with DTG + TDF/FTC • Overall mean change from baseline was 3.1 kg in the DTG + 3TC group and 2.1 kg in the DTG +TDF/FTC group aRelative risk (95% CI) for the DTG + 3TC vs DTG + TDF/FTC group was 0.78 (0.64, 0.95). b3 deaths (acute myocardial infarction, n=1; Burkitt’s lymphoma, n=1; coronary artery disease, n=1), 1 in GEMINI-1 and 2 in GEMINI-2; all were in the DTG + 3TC group and were considered unrelated to the study drug regimen. Cahn et al. IAS 2019; Mexico City, Mexico. Slides WEAB0404LB. OVERALL AE PROFILES WERE SIMILAR; HOWEVER, THERE WAS A LOWER RISK OF DRUG-RELATED AEs IN THE DTG + 3TC GROUP AT WEEK 96 Download Slides: Bit.ly/gemini96wk

  10. *P<0.001 **P<0.005 Plasma/Serum markers Urine markers ** * * * * * Creatinine (µmol/L) GFR fromcreatinine, CKD-EPI (mL/min/1.73 m2) GFR fromcystatin C, CKD-EPI (mL/min/1.73 m2) Protein/Creatinine(g/mol) Retinol-bindingprotein/Creatinine(µg/mmol) Beta-2microglobulin/Creatinine(mg/mmol) aEstimated mean change from baseline in each group was calculated from a repeated measures model adjusting for study, treatment, visit, baseline plasma HIV-1 RNA, baseline CD4+ cell count, age, sex, race, presence of diabetes mellitus, presence of hypertension, baseline biomarker value, treatment and visit interaction, and baseline biomarker value and visit interaction. No assumptions were made about the correlations between participant readings of biomarkers (the correlation matrix for within-participant errors was unstructured). bEstimated from geometric means ratio for baseline and Week 96. Based on the same model as plasma/serum markers except adjusting for loge-transformed baseline biomarker (continuous). Cahn et al. IAS 2019; Mexico City, Mexico. Slides WEAB0404LB. CHANGE IN RENAL BIOMARKERS AT WEEK 96 FAVORS DTG + 3TC Download Slides: Bit.ly/gemini96wk

  11. * *P<0.001 * * * aEstimated mean change from baseline in each group was calculated from a repeated measures model adjusting for study, treatment, visit, baseline plasma HIV-1 RNA, baseline CD4+ cell count, age, sex, race, BMI, smoking status, current vitamin D use, baseline biomarker value, treatment and visit interaction, and baseline biomarker value and visit interaction. No assumptions were made about the correlations between participant readings of biomarkers (the correlation matrix for within-participant errors was unstructured). Cahn et al. IAS 2019; Mexico City, Mexico. Slides WEAB0404LB. CHANGE IN BONE BIOMARKERS AT WEEK 96 FAVORS DTG + 3TC Download Slides: Bit.ly/gemini96wk

  12. *P<0.05 **P<0.001 0.36a 0.12a 0.40a 0.16a 0.16a 0.14a 0.12a 0.11a 0.19a Total cholesterol/HDL cholesterol ratio aAdjusted mean change from baseline to Week 96 based on mixed-effect repeat measures model. Absolute values based on summaries. Changes at Week 96 represented by dashed lines. Direction of change from baseline indicated by arrows above bars. Cahn et al. IAS 2019; Mexico City, Mexico. Slides WEAB0404LB. CHANGE IN SERUM LIPIDS AT WEEK 96 FAVORS THE DTG + TDF/FTC GROUP Download Slides: Bit.ly/gemini96wk

  13. Durability DTG + 3TC maintained non-inferior efficacy over 96 weeks vs DTG + TDF/FTC in ART-naive adults Barrier to Resistance Low rates of confirmed virologic withdrawal through Week 96, and no resistance development in either arm Safety Overall safety and tolerability were comparable between groups Lower risk of drug-related AEs with DTG + 3TC Change in renal and bone biomarkers significantly favors DTG + 3TC Improvements in TC:HDL ratio in both arms These results confirm DTG + 3TC is a compelling treatment option for PLWH Viral Load Rebound Including ‘Blips’ Through 48 Weeks are presented in poster MOPEB231 CONCLUSIONS Cahn et al. IAS 2019; Mexico City, Mexico. Slides WEAB0404LB. Download Slides: Bit.ly/gemini96wk