Phase 3
Completed N=722
An Efficacy, Safety, and Tolerability Study Comparing Dolutegravir (DTG) Plus Lamivudine (3TC) With Dolutegravir Plus Tenofovir/Emtricitabine in Treatment naïve HIV Infected Participants (Gemini 2)
Infection, Human Immunodeficiency Virus · HIV
Source: ClinicalTrials.gov NCT02831764 ↗
Enrolled (actual)
722
Serious AEs
9.8%
Results posted
Apr 2019
Primary outcomePrimary: Percentage of Participants With Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/mL (c/mL) at Week 48 — 93; 94 Percentage of participants
◆ Published Evidence
Highly cited
378citations · ~54 / year
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.
Summary
This study will compare safety, efficacy, and tolerability of a two drug regimen of dolutegravir (DTG) plus (+) lamivudine (3TC) administered once daily with DTG plus two nucleoside reverse transcriptase inhibitors (tenofovir disoproxil fumarate [TDF]/emtricitabine [FTC] fixed dose combination [FDC]) administered once daily in human immunodeficiency virus (HIV) 1 infected adult participants that have not previously received antiretroviral therapy. The study is designed to demonstrate the non inferior antiviral activity of DTG + 3TC regimen to that of DTG + TDF/FTC FDC and will characterise the long term antiviral activity, tolerability and safety of DTG plus 3TC through Week 148. Approximately, 700 participants will be randomised 1:1 to receive DTG + 3TC or DTG + TDF/FTC FDC. Participants will be stratified by screening HIV 1 ribonucleotide nucleic acid (RNA) levels and by screening CD4+ (cluster of differentiation 4) cell count.
Linked Publications (3)
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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.
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Impact of treatment adherence on efficacy of dolutegravir plus lamivudine and dolutegravir plus tenofovir disoproxil fumarate/emtricitabine: pooled analysis of the GEMINI-1 and GEMINI-2 clinical studies.
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Efficacy and Safety Outcomes in Adults Initiating Dolutegravir/Lamivudine With High Viral Load in the GEMINI-1/-2 and STAT Trials.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) <50 Copies/mL (c/mL) at Week 48 |
93; 94 | — |
| SECONDARY Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Week 24 |
94; 94 | — |
| SECONDARY Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Week 96 |
88; 90 | — |
| SECONDARY Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Week 144 |
84; 84 | — |
| SECONDARY Time to Viral Suppression (HIV-1 RNA <50 c/mL) up to Week 144 |
29.0; 29.0 | 0.797 |
| SECONDARY CD4+ Cell Counts at Weeks 24 and 48 |
650.4; 633.0; 688.1; 689.8 | — |
| SECONDARY CD4+ Cell Counts at Week 96 |
734.9; 739.9 | — |
| SECONDARY CD4+ Cell Counts at Week 144 |
763.8; 770.4 | — |
| SECONDARY Changes From Baseline in CD4+ Cell Counts at Week 24 and 48 |
188.8; 163.2; 225.7; 217.2 | 0.043 sig |
| SECONDARY Changes From Baseline in CD4+ Cell Counts at Week 96 |
272.0; 264.6 | 0.635 |
| SECONDARY Changes From Baseline in CD4+ Cell Counts at Week 144 |
301.7; 296.6 | 0.777 |
| SECONDARY Number of Participants With HIV-1 Disease Progression up to Week 144 |
356; 357; 0; 0; 2; 1 | — |
| SECONDARY Number of Participants With Treatment-emergent Genotypic Resistance up to Week 144 |
0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Treatment-emergent Phenotypic Resistance up to Week 144 |
7; 2; 0; 0; 7; 2 | — |
| SECONDARY Number of Participants With Any Adverse Event (AE) and Serious AE (SAE) up to Week 148 |
306; 309; 39; 47 | — |
| SECONDARY Number of Participants With AEs by Maximum Severity Grades up to Week 148 |
54; 54; 211; 205; 32; 43 | — |
| SECONDARY Number of Participants With Any Drug Related AEs and Drug Related AEs by Maximum Grade up to Week 148 |
69; 91; 37; 53; 26; 29 | — |
| SECONDARY Number of Participants With Maximum Post-Baseline Emergent Hematology Toxicities up to Week 144 |
8; 10; 6; 6; 2; 1 | — |
| SECONDARY Number of Participants With Maximum Post-Baseline Emergent Chemistry Toxicities up to Week 144 |
77; 71; 30; 29; 13; 15 | — |
| SECONDARY Number of Participants Who Discontinue Treatment Due to AEs Over Weeks 24, 48, 96 |
6; 4; 8; 8; 10; 12 | — |
| SECONDARY Number of Participants Who Discontinue Treatment Due to AEs Over Week 144 |
13; 16 | — |
| SECONDARY Change From Baseline in Renal Biomarkers-Serum Cystatin C and Serum Retinol Binding Protein (RBP) at Weeks 24, 48 |
-0.04; 0.00; -0.05; -0.04; 1.2; 1.4 | <0.001 sig |
| SECONDARY Change From Baseline in Renal Biomarker-Serum Cystatin C at Week 96 |
-0.09; -0.08 | 0.034 sig |
| SECONDARY Change From Baseline in Renal Biomarker-Serum Cystatin C at Week 144 |
-0.11; -0.08 | 0.006 sig |
| SECONDARY Change From Baseline in Renal Biomarker-Serum RBP at Week 96 |
0.557; 2.483 | — |
| SECONDARY Change From Baseline in Renal Biomarker-Serum RBP at Week 144 |
0.560; 3.813 | — |
| SECONDARY Change From Baseline in Renal Biomarkers-Serum GFR From Cystatin C Adjusted Using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Serum or Plasma GFR From Creatinine Adjusted Using CKD-EPI at Weeks 24, 48 |
3.8; 0.2; 5.4; 3.6; -12.0; -15.4 | <0.001 sig |
| SECONDARY Change From Baseline in Renal Biomarkers-Serum GFR From Cystatin C Adjusted Using CKD-EPI and Serum or Plasma GFR From Creatinine Adjusted for BSA Using CKD-EPI Method at Week 96 |
9.1; 9.5; -14.2; -17.5 | — |
| SECONDARY Change From Baseline in Renal Biomarkers-Serum GFR From Cystatin C Adjusted Using CKD-EPI and Serum or Plasma GFR From Creatinine Adjusted for BSA Using CKD-EPI Method at Week 144 |
10.3; 10.1; -15.5; -18.2 | — |
| SECONDARY Change From Baseline in Renal Biomarker-Serum or Plasma Creatinine at Weeks 24, 48 |
10.51; 13.53; 10.32; 13.44 | <0.001 sig |
| SECONDARY Change From Baseline in Renal Biomarker-Serum or Plasma Creatinine at Week 96 |
11.71; 14.75 | <0.001 sig |
| SECONDARY Change From Baseline in Renal Biomarker-Serum or Plasma Creatinine at Week 144 |
12.28; 15.14 | <0.001 sig |
| SECONDARY Ratio to Baseline in Renal Biomarkers-Urine and Serum Beta-2 Microglobulin (B2M), Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine, Urine RBP 4 and Urine RBP 4/Urine Creatinine at Weeks 24, 48 |
0.809; 0.882; 0.811; 0.887; 0.844; 1.129 | <0.001 sig |
| SECONDARY Ratio to Baseline in Renal Biomarkers- Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine and Urine RBP 4/Urine Creatinine at Week 96 |
0.939; 0.997; 0.844; 1.259; 1.156; 1.069 | 0.338 |
| SECONDARY Ratio to Baseline in Renal Biomarkers- Urine Albumin/Creatinine, Urine B2M/Urine Creatinine, Urine Phosphate, Urine Protein/Creatinine and Urine RBP 4/Urine Creatinine at Week 144 |
1.036; 1.067; 0.872; 1.494; 1.083; 1.084 | 0.658 |
| SECONDARY Change From Baseline in Bone Biomarkers-Serum Bone Specific Alkaline Phosphatase (Bone-ALP), Serum Osteocalcin, Serum Procollagen 1 N-Terminal Propeptide (PINP) and Serum Type I Collagen C-Telopeptides (CTX-1) at Weeks 24, 48 |
0.72; 3.38; 1.24; 4.33; 2.13; 6.80 | <0.001 sig |
| SECONDARY Change From Baseline in Bone Biomarkers-Serum Bone-ALP, Serum Osteocalcin, Serum PINP and Serum Type I CTX-1 at Week 96 |
0.26; 2.39; 0.13; 3.90; 7.0; 19.5 | <0.001 sig |
| SECONDARY Change From Baseline in Bone Biomarkers-Serum Bone-ALP, Serum Osteocalcin, Serum PINP and Serum Type I CTX-1 at Week 144 |
-0.25; 1.88; -1.02; 2.87; -0.1; 9.4 | <0.001 sig |
| SECONDARY Change From Baseline in Bone Biomarker-Serum Vitamin D at Weeks 24, 48 |
11.2; 15.4; 0.3; 0.4 | 0.015 sig |
| SECONDARY Change From Baseline in Bone Biomarker-Serum Vitamin D at Week 96 |
-1.7; 1.3 | 0.048 sig |
| SECONDARY Change From Baseline in Bone Biomarker-Serum Vitamin D at Week 144 |
1.1; 1.4 | 0.887 |
| SECONDARY Percentage Change From Baseline in Fasting Lipids-Serum or Plasma Cholesterol, Serum or Plasma High Density Lipoprotein (HDL) Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides at Weeks 24, 48 |
5.0; -4.5; 9.3; -3.3; 13.9; 7.2 | — |
| SECONDARY Change From Baseline in Fasting Lipids-Serum or Plasma Cholesterol, Serum or Plasma HDL Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides at Week 96 |
0.345; -0.132; 0.185; 0.071; 0.139; -0.160 | — |
| SECONDARY Change From Baseline in Fasting Lipids-Serum or Plasma Cholesterol, Serum or Plasma HDL Cholesterol (Direct), Serum or Plasma LDL Cholesterol (Calculated or Direct) and Serum or Plasma Triglycerides at Week 144 |
0.360; -0.015; 0.180; 0.093; 0.143; -0.085 | — |
| SECONDARY Percentage Change From Baseline in Fasting Lipid-Serum or Plasma Total Cholesterol/HDL Cholesterol Ratio at Weeks 24, 48 |
-4.4; -7.5; -2.8; -4.5 | — |
| SECONDARY Change From Baseline in Fasting Lipid-Serum or Plasma Total Cholesterol/HDL Cholesterol Ratio at Week 96 |
-0.113; -0.395 | — |
| SECONDARY Change From Baseline in Fasting Lipid-Serum or Plasma Total Cholesterol/HDL Cholesterol Ratio at Week 144 |
-0.245; -0.359 | — |
| SECONDARY Percentage of Participants With Grade 2 or Greater Laboratory Abnormalities in Fasting LDL Cholesterol by Weeks 24, 48 |
4; 0; 4; 2 | <0.001 sig |
| SECONDARY Percentage of Participants With Grade 2 or Greater Laboratory Abnormalities in Fasting LDL Cholesterol by Week 96 |
6; 2 | 0.045 sig |
| SECONDARY Percentage of Participants With Grade 2 or Greater Laboratory Abnormalities in Fasting LDL Cholesterol by Week 144 |
6; 4 | 0.160 |
| SECONDARY Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count, Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 24 |
78; 92; 95; 94; 93; 89 | — |
| SECONDARY Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 48 |
78; 96; 95; 94; 89; 87 | — |
| SECONDARY Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 96 |
72; 85; 89; 90; 81; 85 | — |
| SECONDARY Percentage of Participants by Subgroups (by Age, Gender, Baseline CD4+ Cell Count Baseline HIV-1 RNA, Race) With Plasma HIV-1 RNA <50 c/mL at Week 144 |
75; 69; 85; 86; 78; 83 | — |
| SECONDARY Changes From Baseline in CD4+ Cell Counts at Week 24 by Subgroups |
186.01; 148.21; 193.90; 220.71; 167.95; 106.23 | — |
| SECONDARY Changes From Baseline in CD4+ Cell Counts at Week 48 by Subgroups |
215.6; 208.7; 261.8; 248.7; 210.9; 153.2 | — |
| SECONDARY Changes From Baseline in CD4+ Cell Counts at Week 96 by Subgroups |
257.9; 257.5; 312.1; 297.4; 229.4; 202.9 | — |
| SECONDARY Changes From Baseline in CD4+ Cell Counts at Week 144 by Subgroups |
286.8; 277.8; 338.2; 354.7; 264.8; 208.9 | — |
| SECONDARY Change From Baseline in European Quality of Life [EuroQoL] - 5 Dimensions - 5 Levels (EQ-5D-5L) Utility Score at Weeks 4, 24, 48 |
0.0111; 0.0130; 0.0207; 0.0203; 0.0189; 0.0208 | 0.759 |
| SECONDARY Change From Baseline in EQ-5D-5L Utility Score at Week 96 |
0.0168; 0.0171 | 0.957 |
| SECONDARY Change From Baseline in EQ-5D-5L Utility Score at Week 144 |
0.0210; 0.0131 | 0.162 |
| SECONDARY Change From Baseline in EuroQol - 5 Dimensions - 5 Levels (EQ-5D-5L) Thermometer Scores at Weeks 4, 24, 48 |
1.8; 3.1; 3.9; 4.5; 4.0; 4.6 | 0.045 sig |
| SECONDARY Change From Baseline in EQ-5D-5L Thermometer Scores at Week 96 |
4.4; 5.1 | 0.318 |
| SECONDARY Change From Baseline in EQ-5D-5L Thermometer Scores at Week 144 |
4.8; 4.5 | 0.674 |
Eligibility Criteria
Inclusion Criteria
- Must be an HIV 1 infected adult >=18 years of age (or older, if required by local regulations) at the time of signing the informed consent
- An eligible female participant should not be pregnant (as confirmed by a negative serum human chorionic gonadotrophin (hCG) test at Screening and negative urine test at Baseline), not lactating, and at least one of the following conditions applies
- Non reproductive premenopausal women are those that have undergone documented tubal ligation or documented hysteroscopic tubal occlusion procedure with follow up confirmation of bilateral tubal occlusion or documented bilateral oophorectomy or hysterectomy
- Non reproductive premenopausal women are those with 12 months of spontaneous amenorrhea and >=45 years of age
- Women with reproductive potential agree to follow one of the protocol-defined methods for avoiding pregnancy
- Should have screening plasma HIV 1 RNA levels of 1000 c/mL to 1 year from HIV diagnosis or there is documented HIV seronegativity between the last prophylactic dose and the date of HIV diagnosis
- Participants or the participants legal representative capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the consent form and the protocol
- Participants enrolled in France: a participant will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category
Exclusion Criteria
- Women who are breastfeeding or plan to become pregnant or breastfeed during the study
- Any evidence of an active centers for disease control and prevention (CDC) Stage 3 disease (CDC, 2014), except cutaneous Kaposi's sarcoma not requiring systemic therapy and historical or current CD4 cell counts less than 200 cells/mm^3
- Participants with severe hepatic impairment (Class C) as determined by Child Pugh classification
- Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice), cirrhosis, known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones
- Evidence of hepatitis B virus (HBV) infection or HBV surface antibody (anti-HBs or HBsAb) based on:
Participants positive for HBV surface antigen (HBsAg) at screening will be excluded Participants negative for HBV core antibody (anti HBs) but positive for anti HBc (negative HBsAg status) and positive for HBV deoxyribose nucleic acid (DNA) will be excluded; however, participants positive for anti HBc (negative HBsAg status) and positive for anti HBs (past and/or current evidence) are immune to HBV and will not be excluded
- Anticipated need for any hepatitis C virus (HCV) therapy during the first 48 weeks of the study and for HCV therapy based on interferon or any drugs that have a potential for adverse drug:drug interactions with study treatment throughout the entire study period
- Untreated syphilis infection positive RPR at Screening without clear documentation of treatment. Participants who are at least 14 days post completed treatment are eligible
- History or presence of allergy or intolerance to the study drugs or their components or drugs of their class
- Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, non invasive cutaneous squamous cell carcinoma, or cervical, anal or penile intraepithelial neoplasia; other localised malignancies require agreement between the investigator and the Study Medical Monitor for inclusion of the participant
- Participants who in the Investigator's judgment, poses a significant suicidality risk. Recent history of suicidal behaviour and/or suicidal ideation may be considered as evidence of serious suicide risk
- Treatment with an HIV 1 immunotherapeutic vaccine within 90 days of Screening
- Treatment with any of the following agents within 28 days of Screening:
- Radiation therapy,
- Cytotoxic
Data sourced from ClinicalTrials.gov (NCT02831764) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.