Dolutegravir Plus Lamivudine Dual Therapy in Treatment Naïve HIV-1 Patients

• Sponsor: AIDS Clinical Trials Group (Other)
• Overall Status: Completed
• CT.gov ID: NCT02582684
• Collaborator: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Enrollment: 122
• Locations: 26
• Arm: 1
• Actual Duration (Months): 21.6
• Patients Per Site: 4.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This study was done to see if the combination of two anti-HIV medicines, dolutegravir (DTG, Tivicay) and lamivudine (3TC, Epivir) taken once a day, provide a safe, effective, and well-tolerated treatment for HIV. DTG is a type of HIV medicine called an integrase inhibitor; 3TC is a type of HIV medicine called a reverse transcriptase inhibitor. DTG works by blocking integrase and 3TC works by blocking reverse transcriptase, two HIV proteins (enzymes). This prevents HIV from multiplying and lowers the viral load (amount of HIV in the blood). Both DTG and 3TC are currently part of Food and Drug Administration (FDA) recommended regimens along with a third active drug. Since some HIV medicines have side effects and are costly, there is interest in whether HIV can be successfully controlled with fewer than three HIV drugs.

Condition or Disease	Intervention/Treatment	Phase
HIV-1 Infection	Drug: Dolutegravir; Drug: Lamivudine	Phase 2

Detailed Description

This study was a phase II, single-arm, open-label pilot study designed to estimate the efficacy of dolutegravir (DTG) plus lamivudine (3TC) as initial combination ART (antiretroviral therapy) in HIV-1 infected treatment naive participants. The target enrollment was 120 participants with a cap of N=90 participants with screening HIV-1 RNA <= 100,000 copies/mL. The study aimed to enroll >= 20% women. The expected follow-up for each participant was 52 weeks.

Visits occurred at screening, entry, and weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, and 52 from study entry. All signs/symptoms within 30 days prior to entry were recorded. Subsequently, grade 2 or higher rash and all other grade 3 or higher signs and symptoms were recorded. All participants underwent routine monitoring including plasma HIV-1 RNA levels, CD4+ cell count, hematology, chemistry, urinalysis, and pregnancy testing (for women of reproductive potential).

Population-based protease (PR), reverse transcriptase (RT) and integrase genotyping were done at the time of confirmed virologic failure. Plasma samples were stored for potential future studies to assess the impact of adherence, drug-resistant minority viral variants, and DTG exposure on virologic and CD4+ cell count responses to DTG plus 3TC. All participants also underwent UGT1A1 genotyping.

Study Design

• Study Type: Interventional
• Actual Enrollment: 122 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Study to Evaluate Dolutegravir Plus Lamivudine Dual Therapy for the Treatment of Naïve HIV-1-infected Participants
• Actual Study Start Date: Dec 8, 2015
• Actual Primary Completion Date: Feb 28, 2017
• Actual Study Completion Date: Sep 26, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1: DTG 50 mg + 3TC 300 mg Dolutegravir 50mg and Lamivudine 300mg, orally daily	Drug: Dolutegravir; Participants were prescribed 50 mg of DTG orally daily; Other Names: DTG ; Drug: Lamivudine; Participants were prescribed 300 mg of 3TC orally daily.; Other Names: 3TC

Outcome Measures

Primary Outcome Measures

1. Virologic Status at Week 24 [At 24 weeks after study entry]

   Numbers of Participants With Virologic Success, Virologic Non-Success, and no Virologic Data at Week 24 Window are provided below. Virologic success is defined as HIV-1 RNA <50 copies/mL and on study treatment (FDA Snapshot definition).

Secondary Outcome Measures

1. Virologic Status at Week 12 [At 12 weeks after study entry]

   Numbers of Participants With Virologic Success, Virologic Non-Success, and no Virologic Data at Week 12 Window are provided below. Virologic success is defined as HIV-1 RNA <50 copies/mL and on study treatment (FDA Snapshot definition).

2. Virologic Status at Week 48 [At 48 weeks after study entry]

   Numbers of Participants With Virologic Success, Virologic Non-Success, and no Virologic Data at Week 48 Window are provided below. Virologic success is defined as HIV-1 RNA <50 copies/mL and on study treatment (FDA Snapshot definition).

3. Virologic Failure [Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40 and 48]

   Virologic failure is defined as follows: Weeks 16 or 20: confirmed plasma HIV-1 RNA > 400 copies/mL Week 24 or later: confirmed plasma HIV-1 RNA > 200 copies/mL Participants were evaluated for virologic failure regardless of whether on study treatment. Confirmation was determined based on any two consecutive evaluations meeting the virologic failure definition regardless of the time between them. Participants discontinuing the study (for any reason, including death and lost to follow-up) were considered virologic failures if their last measurement met the definition of virologic failure but no confirmatory measurement was obtained. All other participants' follow-up was censored immediately after the last available plasma HIV-1 RNA measurement.

4. Proportion of Participants With Plasma HIV-1 RNA < 50 Copies/mL - Missing = Failure [Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40 and 48]

   Proportion of participants with HIV-1 RNA < 50 copies/mL by week, ITT (Intention To Treat; missing/off study/off treatment = failure) population.

5. Proportion of Participants With Plasma HIV-1 RNA < 200 Copies/mL - Missing = Failure [Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40 and 48]

   Proportion of participants with HIV-1 RNA < 200 copies/mL by week, ITT (missing/off study/off treatment = failure) population.

6. Proportion of Participants With Plasma HIV-1 RNA <50 Copies/mL - Missing = Ignored [Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40 and 48]

   Proportion of participants with HIV-1 RNA < 50 copies/mL by week, ITT (missing = ignored) population.

7. Proportion of Participants With Plasma HIV-1 RNA <200 Copies/mL- ITT Missing = Ignored [Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40 and 48]

   Proportion of participants with HIV-1 RNA < 200 copies/mL by week, ITT (missing = ignored) population.

8. Proportion of Participants With Plasma HIV-1 RNA <50 Copies/mL- As Treated [Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40 and 48]

   Proportion of participants with HIV-1 RNA < 50 copies/mL by week, as treated population.

9. Proportion of Participants With Plasma HIV-1 RNA <200 Copies/mL- As Treated [Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40 and 48]

   Proportion of participants with HIV-1 RNA < 200 copies/mL by week, as treated population.

10. CD4+ Cell Count [Baseline, weeks 4, 12, 24, and 48]

    CD4+ cell counts by study week.

11. Change in CD4+ Cell Count [Baseline, weeks 4, 12, 24, and 48]

    Change in CD4+ cell counts by study week. Change was calculated as value at the later visit minus the value at baseline.

12. Number of HIV-1 Drug Resistance Mutation Occurrences in Participants [at the time of virologic failure]

    Number of HIV-1 drug resistance mutation occurrences participants with virologic failure and FDA snapshot non-successes. Participants that had one drug class resistance mutation may have one or more mutations.

13. Fasting Lipids and Glucose [Baseline and week 48]

    Fasting lipids include: total cholesterol, triglycerides, LDL cholesterol, HDL cholesterol, and glucose. Fasting was set to be 8 hours prior to the sample collection.

14. Creatinine Clearance [Baseline, weeks 4, 12, 24, 32, 40 and 48]

    Creatinine clearance was estimated by the Cockcroft-Gault equation.

15. Number of Participants With Grade 3 of Higher Adverse Events [from study treatment dispensation through up to week 52 or until study discontinuation]

    Number of participants who experienced an AE (sign/symptom or laboratory abnormality) of Grade 3 or higher. The AEs were graded by the clinicians according to the Division of AIDS (DAIDS) AE Grading Table (see reference in the Protocol Section) as follows: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Potentially Life-Threatening.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

NOTE: Further information on the eligibility criteria can be found in the study protocol.

Inclusion Criteria:

• HIV-1 infection.

• Plasma HIV-1 RNA ≥1000 copies/mL and <500,000 copies/mL obtained within 90 days prior to study entry.

• No evidence of any RT, any integrase, or major protease resistance mutation (according to the 2014 IAS-USA drug resistance mutations list, available at https://www.iasusa.org/sites/default/files/tam/22-3-642.pdf) based on pre-ARV (antiretroviral) treatment genotype performed any time prior to study entry.

• ARV treatment drug-naive (defined as no previous ARV treatment at any time prior to study entry, with the exception of successful post-exposure prophylaxis (PEP) or pre-exposure prophylaxis (PrEP).

• The following laboratory values obtained within 45 days prior to study entry:

• ANC (absolute neutrophil count) ≥750/mm^3

• Hemoglobin ≥10.0 g/dL

• Platelets ≥ 50,000/mm^3

• Calculated creatinine clearance (CrCl) ≥50 mL/min, as estimated by the Cockcroft-Gault equation

• AST (aspartate aminotransferase) <5 x ULN (upper limit of normal)

• ALT (alanine aminotransferase) <5x ULN

• Total bilirubin <1.5 x ULN

• Hepatitis B surface antigen negative within 45 days prior to study entry.

• For women with reproductive potential, negative serum or urine pregnancy test at screening and within 48 hours prior to study entry.

• If participating in sexual activity that could lead to pregnancy, female participants with reproductive potential must have agreed to use one form of contraceptive as listed in the protocol while receiving protocol-specified medications and for 30 days after stopping the medications.

• Ability and willingness of participant or legal representative to provide informed consent.

Exclusion Criteria:

• Serious illness requiring systemic treatment and/or hospitalization.

• Treatment within 30 days prior to study entry with immune modulators such as systemic steroids, interleukins, interferons, granulocyte colony-stimulating factor (G-CSF), erythropoietin, or any investigational therapy.

• Pregnancy or breastfeeding.

• Receipt of systemic cytotoxic chemotherapy or dofetilide.

• Known allergy/sensitivity to any of the study drugs or their formulations.

• Active drug or alcohol use or dependence that may interfere with adherence to study requirements, in the opinion of the site investigator.

• Active hepatitis C virus (HCV) treatment or anticipated need for treatment within study period.

• Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).

• Severe hepatic impairment (Class C) as determined by Child-Pugh classification.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Southern California CRS (1201)	Los Angeles	California	United States	90033
2	UCLA CARE Center CRS (601)	Los Angeles	California	United States	90095
3	Ucsd, Avrc Crs (701)	San Diego	California	United States	92103
4	Harbor-UCLA Med. Ctr. CRS (603)	Torrance	California	United States	90502
5	University of Colorado Hospital CRS (6101)	Aurora	Colorado	United States	80045
6	Univ. of Miami AIDS CRS (901)	Miami	Florida	United States	33136
7	The Ponce de Leon Center CRS (5802)	Atlanta	Georgia	United States	30308
8	Northwestern University CRS (2701)	Chicago	Illinois	United States	60611
9	Rush Univ. Med. Ctr. ACTG CRS (2702)	Chicago	Illinois	United States	60612
10	Massachusetts General Hospital ACTG CRS (101)	Boston	Massachusetts	United States	02114
11	Brigham and Women's Hosp. ACTG CRS (107)	Boston	Massachusetts	United States	02115
12	Washington University CRS (2101)	Saint Louis	Missouri	United States	63110
13	Cornell CRS (7804)	New York	New York	United States	10011
14	Weill Med. College of Cornell Univ., The Cornell CTU -Chelsea (7803)	New York	New York	United States	10011
15	Columbia Physicians and Surgeons CRS (30329)	New York	New York	United States	10032
16	University of Rochester Adult HIV Therapeutic Strategies Network CRS (31787)	Rochester	New York	United States	14642
17	3201 Chapel Hill CRS	Chapel Hill	North Carolina	United States	27516
18	Greensboro CRS (3203)	Greensboro	North Carolina	United States	27401
19	Univ. of Cincinnati CRS (2401)	Cincinnati	Ohio	United States	45267
20	The Ohio State Univ. AIDS CRS (2301)	Columbus	Ohio	United States	43210
21	Hosp. of the Univ. of Pennsylvania CRS (6201)	Philadelphia	Pennsylvania	United States	19104
22	The Miriam Hospital ACTG CRS (2951)	Providence	Rhode Island	United States	02906
23	Vanderbilt Therapeutics CRS (3652)	Nashville	Tennessee	United States	37204
24	31443 Trinity Health and Wellness Center CRS	Dallas	Texas	United States	75208
25	Houston AIDS Research Team CRS (31473)	Houston	Texas	United States	77030
26	Puerto Rico-AIDS CRS (5401)	San Juan		Puerto Rico	00935

Sponsors and Collaborators

• AIDS Clinical Trials Group
• National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

• Study Chair: Roy Gulick, MD, MPH, Weill Medical College of Cornell University
• Study Chair: Babafemi Taiwo, MBBS, Northwestern University

Study Documents (Full-Text)

• Statistical Analysis Plan - Sep 28, 2016
• Study Protocol - Aug 14, 2015

More Information

Additional Information:

• DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0 November 2014
• FDA Snapshot Definition (refer to Appendix A in FDA Snapshot PDF)
• DAIDS Adverse Events Manual, Version 2.0 January 2010

Publications

None provided.

• Responsible Party: AIDS Clinical Trials Group
• ClinicalTrials.gov Identifier: NCT02582684
• Other Study ID Numbers: ACTG A5353; 2UM1AI068636
• First Posted: Oct 21, 2015
• Last Update Posted: May 9, 2018
• Last Verified: Apr 1, 2018

• Additional relevant MeSH terms: Lamivudine; Dolutegravir

Study Results

Participant Flow

Pre-assignment Detail	A total of 122 participants were accrued.

Arm/Group Title	Arm 1: DTG 50 MG + 3TC 300 mg
Arm/Group Description	Dolutegravir: Participants were prescribed 50 mg of DTG orally daily Lamivudine: Participants were prescribed 300 mg of 3TC orally daily.
Period Title: Overall Study
STARTED	122
COMPLETED	105
NOT COMPLETED	17

Baseline Characteristics

Arm/Group Title	Arm 1: DTG 50 MG + 3TC 300 mg
Arm/Group Description	Dolutegravir: Participants were prescribed 50 mg of DTG orally daily Lamivudine: Participants were prescribed 300 mg of 3TC orally daily.
Overall Participants	120
Age (Years) [Median (Inter-Quartile Range) ]
Age	30
Age, Customized (Count of Participants)
18-29 years	58 48.3%
30-39 years	29 24.2%
40-49 years	17 14.2%
50-59 years	12 10%
>= 60 years	4 3.3%
Sex: Female, Male (Count of Participants)
Female	16 13.3%
Male	104 86.7%
Race/Ethnicity, Customized (Count of Participants)
White Non-Hispanic	34 28.3%
Black Non-Hispanic	48 40%
Hispanic (Regardless of Race)	32 26.7%
Asian, Pacific Islander	2 1.7%
More than one race	2 1.7%
Does not want to report	2 1.7%
Region of Enrollment (Count of Participants)
Puerto Rico	3 2.5%
United States	117 97.5%
Intravenous Drug Use (Count of Participants)
Never	113 94.2%
Currently	2 1.7%
Previously	5 4.2%
CD4 Count, Continuous (cells/mm^3) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [cells/mm^3]	387
CD4 Count, Categorized (Count of Participants)
<200 cells/mm^3	16 13.3%
200-349 cells/mm^3	27 22.5%
350-499 cells/mm^3	30 25%
500-649 cells/mm^3	19 15.8%
650-799 cells/mm^3	15 12.5%
>=800 cells/mm^3	11 9.2%
Missing	2 1.7%
CD8 Count (cells/mm^3) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [cells/mm^3]	871
CD4/CD8 Ratio (ratio) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [ratio]	0.44
Screening HIV-1 RNA (log10 copies/mL) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [log10 copies/mL]	4.70
Baseline HIV-1 RNA (log10 copies/mL) [Median (Inter-Quartile Range) ]
Median (Inter-Quartile Range) [log10 copies/mL]	4.61
Baseline HIV-1 RNA Category (Count of Participants)
< 1,000 copies/mL	1 0.8%
1,000 - 9,999 copies/mL	34 28.3%
10,000 - 99,999 copies/mL	48 40%
100,000 - 200,000 copies/mL	23 19.2%
> 200,000 copies/mL	14 11.7%
Hepatitis C Antibody Status (Count of Participants)
Positive	4 3.3%
Negative	116 96.7%
Post-exposure Prophylaxis or Pre-Exposure Prophylaxis History (Count of Participants)
Yes	1 0.8%
No	119 99.2%

Outcome Measures

1. Primary Outcome

Title	Virologic Status at Week 24
Description	Numbers of Participants With Virologic Success, Virologic Non-Success, and no Virologic Data at Week 24 Window are provided below. Virologic success is defined as HIV-1 RNA <50 copies/mL and on study treatment (FDA Snapshot definition).
Time Frame	At 24 weeks after study entry

Outcome Measure Data

Analysis Population Description

All eligible participants enrolled.

Arm/Group Title	Arm 1: DTG 50 MG + 3TC 300 mg
Arm/Group Description	Dolutegravir: Participants were prescribed 50 mg of DTG orally daily Lamivudine: Participants were prescribed 300 mg of 3TC orally daily.
Measure Participants	120
Virologic success	108 90%
Virologic non-success	5 4.2%
No virologic data in window	7 5.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm 1: DTG 50 MG + 3TC 300 mg
	Comments
	Type of Statistical Test	Other
	Comments	Binomial Proportion of Participants with Virologic Success and 95% Confidence Interval
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	proportion
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 95%; 0.83 to 0.95
	Parameter Dispersion	Type: Value:
	Estimation Comments	Confidence interval was calculated using the Clopper-Pearson exact method.

2. Secondary Outcome

Title	Virologic Status at Week 12
Description	Numbers of Participants With Virologic Success, Virologic Non-Success, and no Virologic Data at Week 12 Window are provided below. Virologic success is defined as HIV-1 RNA <50 copies/mL and on study treatment (FDA Snapshot definition).
Time Frame	At 12 weeks after study entry

Outcome Measure Data

Analysis Population Description

All eligible participants enrolled.

Arm/Group Title	Arm 1: DTG 50 MG + 3TC 300 mg
Arm/Group Description	Dolutegravir: Participants were prescribed 50 mg of DTG orally daily Lamivudine: Participants were prescribed 300 mg of 3TC orally daily.
Measure Participants	120
Virologic success	107 89.2%
Virologic non-success	7 5.8%
No virologic data in window	6 5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm 1: DTG 50 MG + 3TC 300 mg
	Comments
	Type of Statistical Test	Other
	Comments	Binomial Proportion of Participants with Virologic Success and 95% Confidence Interval
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Proportion
	Estimated Value	0.89
	Confidence Interval	(2-Sided) 95%; 0.82 to 0.94
	Parameter Dispersion	Type: Value:
	Estimation Comments	Confidence interval was calculated using the Clopper-Pearson exact method.

3. Secondary Outcome

Title	Virologic Status at Week 48
Description	Numbers of Participants With Virologic Success, Virologic Non-Success, and no Virologic Data at Week 48 Window are provided below. Virologic success is defined as HIV-1 RNA <50 copies/mL and on study treatment (FDA Snapshot definition).
Time Frame	At 48 weeks after study entry

Outcome Measure Data

Analysis Population Description

All eligible participants enrolled.

Arm/Group Title	Arm 1: DTG 50 MG + 3TC 300 mg
Arm/Group Description	Dolutegravir: Participants were prescribed 50 mg of DTG orally daily Lamivudine: Participants were prescribed 300 mg of 3TC orally daily.
Measure Participants	120
Virologic success	102 85%
Virologic non-success	6 5%
No virologic data in window	12 10%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Arm 1: DTG 50 MG + 3TC 300 mg
	Comments
	Type of Statistical Test	Other
	Comments	Binomial Proportion of Participants with Virologic Success and 95% Confidence Interval
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	proportion
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95%; 0.77 to 0.91
	Parameter Dispersion	Type: Value:
	Estimation Comments	Confidence interval was calculated using the Clopper-Pearson exact method.

4. Secondary Outcome

Title	Virologic Failure
Description	Virologic failure is defined as follows: Weeks 16 or 20: confirmed plasma HIV-1 RNA > 400 copies/mL Week 24 or later: confirmed plasma HIV-1 RNA > 200 copies/mL Participants were evaluated for virologic failure regardless of whether on study treatment. Confirmation was determined based on any two consecutive evaluations meeting the virologic failure definition regardless of the time between them. Participants discontinuing the study (for any reason, including death and lost to follow-up) were considered virologic failures if their last measurement met the definition of virologic failure but no confirmatory measurement was obtained. All other participants' follow-up was censored immediately after the last available plasma HIV-1 RNA measurement.
Time Frame	Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40 and 48

Outcome Measure Data

Analysis Population Description

All eligible participants enrolled.

Arm/Group Title	Arm 1: DTG 50 MG + 3TC 300 mg
Arm/Group Description	Dolutegravir: Participants were prescribed 50 mg of DTG orally daily Lamivudine: Participants were prescribed 300 mg of 3TC orally daily.
Measure Participants	120
Yes	4 3.3%
No	116 96.7%

5. Secondary Outcome

Title	Proportion of Participants With Plasma HIV-1 RNA < 50 Copies/mL - Missing = Failure
Description	Proportion of participants with HIV-1 RNA < 50 copies/mL by week, ITT (Intention To Treat; missing/off study/off treatment = failure) population.
Time Frame	Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40 and 48

Outcome Measure Data

Analysis Population Description

The population here is the ITT (missing/off study/off treatment = failure) population. The numerator includes participants with HIV-1 RNA < 50 copies/mL and still on initial treatment; the denominator includes all participants with potential for the given week of follow-up based on the date of registration.

Arm/Group Title	Arm 1: DTG 50 MG + 3TC 300 mg
Arm/Group Description	Dolutegravir: Participants were prescribed 50 mg of DTG orally daily Lamivudine: Participants were prescribed 300 mg of 3TC orally daily.
Measure Participants	120
Week 2	0.40 0.3%
Week 4	0.68 0.6%
Week 8	0.85 0.7%
Week 12	0.89 0.7%
Week 16	0.88 0.7%
Week 20	0.90 0.8%
Week 24	0.90 0.8%
Week 32	0.88 0.7%
Week 40	0.89 0.7%
Week 48	0.84 0.7%

6. Secondary Outcome

Title	Proportion of Participants With Plasma HIV-1 RNA < 200 Copies/mL - Missing = Failure
Description	Proportion of participants with HIV-1 RNA < 200 copies/mL by week, ITT (missing/off study/off treatment = failure) population.
Time Frame	Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40 and 48

Outcome Measure Data

Analysis Population Description

The population here is the ITT (missing/off study/off treatment = failure) population. The numerator includes participants with HIV-1 RNA < 200 copies/mL and still on initial treatment; the denominator includes all participants with potential for the given week of follow-up based on the date of registration.

Arm/Group Title	Arm 1: DTG 50 MG + 3TC 300 mg
Arm/Group Description	Dolutegravir: Participants were prescribed 50 mg of DTG orally daily Lamivudine: Participants were prescribed 300 mg of 3TC orally daily.
Measure Participants	120
Week 2	0.68 0.6%
Week 4	0.90 0.8%
Week 8	0.95 0.8%
Week 12	0.93 0.8%
Week 16	0.92 0.8%
Week 20	0.95 0.8%
Week 24	0.92 0.8%
Week 32	0.89 0.7%
Week 40	0.91 0.8%
Week 48	0.87 0.7%

7. Secondary Outcome

Title	Proportion of Participants With Plasma HIV-1 RNA <50 Copies/mL - Missing = Ignored
Description	Proportion of participants with HIV-1 RNA < 50 copies/mL by week, ITT (missing = ignored) population.
Time Frame	Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40 and 48

Outcome Measure Data

Analysis Population Description

ITT Missing = Ignored. The numerator includes participants with HIV-1 RNA < 50 copies/mL; the denominator includes all participants with an HIV-1 RNA evaluation at the given week.

Arm/Group Title	Arm 1: DTG 50 MG + 3TC 300 mg
Arm/Group Description	Dolutegravir: Participants were prescribed 50 mg of DTG orally daily Lamivudine: Participants were prescribed 300 mg of 3TC orally daily.
Measure Participants	120
Week 2	0.41 0.3%
Week 4	0.70 0.6%
Week 8	0.88 0.7%
Week 12	0.94 0.8%
Week 16	0.94 0.8%
Week 20	0.94 0.8%
Week 24	0.96 0.8%
Week 32	0.93 0.8%
Week 40	0.95 0.8%
Week 48	0.94 0.8%

8. Secondary Outcome

Title	Proportion of Participants With Plasma HIV-1 RNA <200 Copies/mL- ITT Missing = Ignored
Description	Proportion of participants with HIV-1 RNA < 200 copies/mL by week, ITT (missing = ignored) population.
Time Frame	Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40 and 48

Outcome Measure Data

Analysis Population Description

ITT Missing = Ignored. The numerator includes participants with HIV-1 RNA < 200 copies/mL; the denominator includes all participants with an HIV-1 RNA evaluation at the given week.

Arm/Group Title	Arm 1: DTG 50 MG + 3TC 300 mg
Arm/Group Description	Dolutegravir: Participants were prescribed 50 mg of DTG orally daily Lamivudine: Participants were prescribed 300 mg of 3TC orally daily.
Measure Participants	120
Week 2	0.71 0.6%
Week 4	0.94 0.8%
Week 8	0.98 0.8%
Week 12	0.98 0.8%
Week 16	0.98 0.8%
Week 20	0.99 0.8%
Week 24	0.97 0.8%
Week 32	0.95 0.8%
Week 40	0.96 0.8%
Week 48	0.96 0.8%

9. Secondary Outcome

Title	Proportion of Participants With Plasma HIV-1 RNA <50 Copies/mL- As Treated
Description	Proportion of participants with HIV-1 RNA < 50 copies/mL by week, as treated population.
Time Frame	Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40 and 48

Outcome Measure Data

Analysis Population Description

As Treated: purely virologic missing = ignored. The numerator includes participants with HIV-1 RNA < 50 copies/mL and still on initial treatment; the denominator includes participants on initial treatment with an HIV-1 RNA evaluation at the given week.

Arm/Group Title	Arm 1: DTG 50 MG + 3TC 300 mg
Arm/Group Description	Dolutegravir: Participants were prescribed 50 mg of DTG orally daily Lamivudine: Participants were prescribed 300 mg of 3TC orally daily.
Measure Participants	120
Week 2	0.41 0.3%
Week 4	0.70 0.6%
Week 8	0.88 0.7%
Week 12	0.94 0.8%
Week 16	0.94 0.8%
Week 20	0.94 0.8%
Week 24	0.96 0.8%
Week 32	0.95 0.8%
Week 40	0.97 0.8%
Week 48	0.97 0.8%

10. Secondary Outcome

Title	Proportion of Participants With Plasma HIV-1 RNA <200 Copies/mL- As Treated
Description	Proportion of participants with HIV-1 RNA < 200 copies/mL by week, as treated population.
Time Frame	Weeks 2, 4, 8, 12, 16, 20, 24, 32, 40 and 48

Outcome Measure Data

Analysis Population Description

As Treated: purely virologic missing=ignored. The numerator includes participants with HIV-1 RNA < 200 copies/mL and still on initial treatment; the denominator includes participants on initial treatment with an HIV-1 RNA evaluation at the given week.

Arm/Group Title	Arm 1: DTG 50 MG + 3TC 300 mg
Arm/Group Description	Dolutegravir: Participants were prescribed 50 mg of DTG orally daily Lamivudine: Participants were prescribed 300 mg of 3TC orally daily.
Measure Participants	120
Week 2	0.71 0.6%
Week 4	0.94 0.8%
Week 8	0.98 0.8%
Week 12	0.98 0.8%
Week 16	0.98 0.8%
Week 20	0.99 0.8%
Week 24	0.98 0.8%
Week 32	0.97 0.8%
Week 40	0.99 0.8%
Week 48	1.00 0.8%

11. Secondary Outcome

Title	CD4+ Cell Count
Description	CD4+ cell counts by study week.
Time Frame	Baseline, weeks 4, 12, 24, and 48

Outcome Measure Data

Analysis Population Description

All eligible participants enrolled with CD4 count results available at a given visit.

Arm/Group Title	Arm 1: DTG 50 MG + 3TC 300 mg
Arm/Group Description	Dolutegravir: Participants were prescribed 50 mg of DTG orally daily Lamivudine: Participants were prescribed 300 mg of 3TC orally daily.
Measure Participants	120
Week 0	387
Week 4	473
Week 12	520
Week 24	582
Week 48	579

12. Secondary Outcome

Title	Change in CD4+ Cell Count
Description	Change in CD4+ cell counts by study week. Change was calculated as value at the later visit minus the value at baseline.
Time Frame	Baseline, weeks 4, 12, 24, and 48

Outcome Measure Data

Analysis Population Description

All eligible participants enrolled with CD4 cell count results available at baseline and the given visit.

Arm/Group Title	Arm 1: DTG 50 MG + 3TC 300 mg
Arm/Group Description	Dolutegravir: Participants were prescribed 50 mg of DTG orally daily Lamivudine: Participants were prescribed 300 mg of 3TC orally daily.
Measure Participants	120
Change from Baseline to Week 4	78
Change from Baseline to Week 12	122
Change from Baseline to Week 24	167
Change from Baseline to Week 48	182

13. Secondary Outcome

Title	Number of HIV-1 Drug Resistance Mutation Occurrences in Participants
Description	Number of HIV-1 drug resistance mutation occurrences participants with virologic failure and FDA snapshot non-successes. Participants that had one drug class resistance mutation may have one or more mutations.
Time Frame	at the time of virologic failure

Outcome Measure Data

Analysis Population Description

Of the enrolled eligible participants, those with virologic failures had resistance testing done.

Arm/Group Title	Arm 1: DTG 50 MG + 3TC 300 mg
Arm/Group Description	Dolutegravir: Participants were prescribed 50 mg of DTG orally daily Lamivudine: Participants were prescribed 300 mg of 3TC orally daily.
Measure Participants	4
NRTI mutation	1
NNRTI mutation	1
INI mutation	1

14. Secondary Outcome

Title	Fasting Lipids and Glucose
Description	Fasting lipids include: total cholesterol, triglycerides, LDL cholesterol, HDL cholesterol, and glucose. Fasting was set to be 8 hours prior to the sample collection.
Time Frame	Baseline and week 48

Outcome Measure Data

Analysis Population Description

All eligible participants enrolled with lipids results available at a given time point.

Arm/Group Title	Arm 1: DTG 50 MG + 3TC 300 mg
Arm/Group Description	Dolutegravir: Participants were prescribed 50 mg of DTG orally daily Lamivudine: Participants were prescribed 300 mg of 3TC orally daily.
Measure Participants	120
Baseline Total Cholesterol	151
Week 48 Total Cholesterol	154
Baseline LDL Cholesterol	85
Week 48 LDL Cholesterol	86
Baseline HDL Cholesterol	39
Week 48 HDL Cholesterol	46
Baseline Triglycerides	91
Week 48 Triglycerides	98
Baseline Glucose	84
Week 48 Glucose	86

15. Secondary Outcome

Title	Creatinine Clearance
Description	Creatinine clearance was estimated by the Cockcroft-Gault equation.
Time Frame	Baseline, weeks 4, 12, 24, 32, 40 and 48

Outcome Measure Data

Analysis Population Description

All eligible participants enrolled with creatinine clearance results available at a given time point.

Arm/Group Title	Arm 1: DTG 50 MG + 3TC 300 mg
Arm/Group Description	Dolutegravir: Participants were prescribed 50 mg of DTG orally daily Lamivudine: Participants were prescribed 300 mg of 3TC orally daily.
Measure Participants	120
Week 0	126.0
Week 4	112.9
Week 12	112.0
Week 24	114.7
Week 32	115.5
Week 40	112.7
Week 48	114.4

16. Secondary Outcome

Title	Number of Participants With Grade 3 of Higher Adverse Events
Description	Number of participants who experienced an AE (sign/symptom or laboratory abnormality) of Grade 3 or higher. The AEs were graded by the clinicians according to the Division of AIDS (DAIDS) AE Grading Table (see reference in the Protocol Section) as follows: Grade 1=Mild, Grade 2=Moderate, Grade 3=Severe, Grade 4=Potentially Life-Threatening.
Time Frame	from study treatment dispensation through up to week 52 or until study discontinuation

Outcome Measure Data

Analysis Population Description

All eligible participants enrolled.

Arm/Group Title	Arm 1: DTG 50 MG + 3TC 300 mg
Arm/Group Description	Dolutegravir: Participants were prescribed 50 mg of DTG orally daily Lamivudine: Participants were prescribed 300 mg of 3TC orally daily.
Measure Participants	120
Count of Participants [Participants]	16 13.3%

Adverse Events

Time Frame	From study entry through up to week 52 or until study discontinuation
Adverse Event Reporting Description	The protocol required reporting of all diagnoses (identified by the ACTG criteria for clinical events and other diseases), signs/symptoms and laboratory values of >= Grade 3 and events that led to a change in treatment or that met ICH, EAE, or SAE guidelines, regardless of grade. Creatinine and creatinine clearance were reported regardless of grade. The DAIDS AE Grading Table (Version 2.0) and Expedited AE Manual (Version 2.0) were used.
Arm/Group Title	Arm 1: DTG 50 MG + 3TC 300 mg
Arm/Group Description	Dolutegravir: Participants were prescribed 50 mg of DTG orally daily Lamivudine: Participants were prescribed 300 mg of 3TC orally daily.
All Cause Mortality
	Arm 1: DTG 50 MG + 3TC 300 mg
	Affected / at Risk (%)	# Events
Total	0/122 (0%)
Serious Adverse Events
	Arm 1: DTG 50 MG + 3TC 300 mg
	Affected / at Risk (%)	# Events
Total	3/122 (2.5%)
Psychiatric disorders
Suicidal ideation	3/122 (2.5%)
Suicide attempt	1/122 (0.8%)
Other (Not Including Serious) Adverse Events
	Arm 1: DTG 50 MG + 3TC 300 mg
	Affected / at Risk (%)	# Events
Total	75/122 (61.5%)
Infections and infestations
Urethritis gonococcal	7/122 (5.7%)
Investigations
Alanine aminotransferase increased	8/122 (6.6%)
Aspartate aminotransferase increased	10/122 (8.2%)
Blood cholesterol increased	20/122 (16.4%)
Blood creatinine abnormal	10/122 (8.2%)
Blood glucose increased	11/122 (9%)
Blood sodium decreased	7/122 (5.7%)
Blood triglycerides increased	30/122 (24.6%)
Low density lipoprotein increased	19/122 (15.6%)
Neutrophil count decreased	12/122 (9.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.