Safety and Efficacy of Dolutegravir/Lamivudine (DTG/3TC) in Therapy-naive Human Immunodeficiency Virus-1 (HIV-1) Infected Adolescents

NCT03682848 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: 205861
• Study Type: interventional
• Target: 32
• Locations: 3 countries
• Sites: 8

Brief Summary

First-line antiretroviral regimens are highly efficacious and generally well tolerated. However, as these regimens need to be taken life-long, there is growing concern about long-term toxicities associated with these regimens. Thus, there is great interest from participants and clinicians in unique regimens that might avoid such toxicities by minimizing the number of antiretrovirals without sacrificing long-term antiviral efficacy. DTG plus 3TC is a novel, well-tolerated first-line regimen for HIV-infected treatment- naive participants, limiting the risk of many common adverse reactions associated with other antiretroviral drugs. This study was designed to evaluate the efficacy and safety of DTG/3TC as an FDC in ART-naive HIV-1-infected adolescents who weighed at least 25 kilograms (kg). The study consisted of a Screening Phase (up to 28 days prior to the first dose of drug), followed by a Treatment Phase (up to 48 weeks). Participants who successfully completed 48 weeks of therapy and continued to receive benefit from DTG/3TC FDC were eligible to enter a 96-week Extension Phase. Study participants who successfully completed both the Treatment Phase through 48 weeks and the Extension Phase through 144 weeks and continued to receive benefit from this two-drug regimen were to continue receiving DTG/3TC FDC in a Continuation Phase (after Week 144) until DTG and 3TC were both locally approved for use as part of a dual regimen and the single entities of DTG and 3TC were available to participants (e.g., through public health services), or the DTG/3TC FDC tablet, if required by local regulations, was locally approved and available (e.g., commercially or through public health services), or the participant no longer derived clinical benefit, or the participant met a protocol-defined reason for discontinuation. All participants received the FDC of DTG/3TC (50/300 milligrams) once daily.

Conditions

HIV Infections

Keywords

Viral load; Dolutegravir; Lamivudine; HIV-1; Fixed dose combination; DOVATO

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Plasma Human Immunodeficiency Virus Type 1 (HIV-1) Ribonucleic Acid (RNA) Less Than 50 Copies Per Milliliter (c/mL) at Week 48

  Percentage of participants with plasma HIV-1 RNA \<50 c/mL was assessed at Week 48 according to the Food and Drug Administration (FDA) snapshot algorithm.

  Week 48

Secondary Outcomes (41)

• Percentage of Participants With Plasma HIV-1 RNA <200 c/mL at Week 24

  Week 24

• Percentage of Participants With Plasma HIV-1 RNA <200 c/mL at Week 96

  Week 96

• Percentage of Participants With Plasma HIV-1 RNA <200 c/mL at Week 144

  Week 144

• Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Week 24

  Week 24

• Percentage of Participants With Plasma HIV-1 RNA <50 c/mL at Week 96

  Week 96

Study Arms (1)

DTG/3TC FDC

EXPERIMENTAL

Participants received dolutegravir/lamivudine (DTG/3TC) (50/300 mg) Fixed Dose Combination (FDC) tablets orally once daily.

Drug: DTG + 3TC FDC

Interventions

DTG + 3TC FDC DRUG

DTG + 3TC FDC was available as a 50/300 mg tablet to be given orally once daily.

DTG/3TC FDC

Eligibility Criteria

• Age: 12 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• HIV-1-infected adolescents were 12 to \<18 years of age at the time of signing the informed consent form.
• Weight was \>25 kg at the time of signing the informed consent form.
• Screening plasma HIV-1 RNA was between 1,000 and =500,000 c/mL.
• Participants were antiretroviral-naive (defined as having had no prior therapy with any antiretroviral agent for the treatment of HIV following a diagnosis of HIV-1 infection). Participants who had received ART for prevention of mother-to-child transmission of HIV in the first 3 months of life were allowed. Participants who had received HIV post-exposure prophylaxis (PEP) or pre-exposure prophylaxis (PrEP) in the past were allowed as long as the last PEP/PrEP dose was = 6 months before HIV diagnosis or there was documented HIV seronegativity at least 2 months after the last prophylactic dose and prior to the date of HIV diagnosis.
• Male and female participants were included. A female participant was eligible to participate if she was not pregnant (as confirmed by a negative serum human chorionic gonadotropin \[hCG\] test at Screening and a negative urine hCG test before Enrollment) and not lactating. Female participants of child-bearing potential who were engaging in sexual activity that could have led to pregnancy had to agree to use one birth-control method from 28 days prior to the first dose of study medication until 4 weeks after the last dose of study medication (and completion of the follow-up visit). Condoms were additionally recommended, as appropriate use was the only contraceptive method effective in preventing HIV-1 transmission. The investigator was responsible for ensuring that participants understood how to properly use these contraceptive methods. All participants in the study were also counseled on safer sexual practices, including the use and benefit/risk of effective barrier methods (e.g., male condoms), as well as on the risk of HIV transmission to an uninfected partner.
• The participant's parent(s) or legal guardian, or the participant, was capable of giving signed informed consent.

You may not qualify if:

• Females who were breastfeeding or who planned to become pregnant or breastfeed during the study were excluded.
• Participants with severe hepatic impairment (Class C) as determined by the Child-Pugh classification were excluded.
• Participants with unstable liver disease (defined by ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, or persistent jaundice), cirrhosis, or known biliary abnormalities (except Gilbert's syndrome or asymptomatic gallstones) were excluded.
• Participants with an anticipated need for any HCV therapy during the first 48 weeks of the study-and for any HCV therapy based on interferon or drugs with potential adverse drug-drug interactions with study treatment throughout the entire study period-were excluded.
• Participants with a history of sensitivity to any study medication or its components, or to drugs of the same class, or a history of drug or other allergy that, in the opinion of the Investigator or Medical Monitor, contraindicated participation, were excluded.
• Participants who, in the investigator's judgment, posed a significant suicide risk were excluded. A recent history of suicidal behavior and/or suicidal ideation could have been considered evidence of serious suicide risk.
• Children who were wards of the state or government were excluded.

Sponsors & Collaborators

• ViiV Healthcare: lead

Study Sites (8)

GSK Investigational Site

Kericho, 20200, Kenya

Location

GSK Investigational Site

Kisumu, 40100, Kenya

Location

GSK Investigational Site

Cape Town, 7500, South Africa

Location

GSK Investigational Site

Durban, 4001, South Africa

Location

GSK Investigational Site

Johannesburg, 1862, South Africa

Location

GSK Investigational Site

Bangkok, 10330, Thailand

Location

GSK Investigational Site

Bangkok, 10700, Thailand

Location

GSK Investigational Site

Chiang Mai, 50200, Thailand

Location

Related Publications (1)

• Puthanakit T, Aurpibul L, Lopez M, Wang M, Ciuffa M, Bontempo G, Cheung SYA, Deprez I, Buchanan AM, Vavro C, McKenna M, Min S, Tan LK. Efficacy and Safety of the Two-Drug Regimen Dolutegravir-Lamivudine in Adolescents Living With HIV-1 Naive to Antiretroviral Therapy at 48 Weeks (DANCE): A Single-Arm, Open-Label, Phase 3b Trial. J Acquir Immune Defic Syndr. 2025 Jun 1;99(2):202-210. doi: 10.1097/QAI.0000000000003655.

  PMID: 39988749 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

dolutegravir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  ViiV Healthcare

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Masking Details: This was an open-label study hence, there was no masking.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: All participants received FDC of DTG/3TC (50/300 mg) once daily.

Study Record Dates

• First Submitted: September 21, 2018
• First Posted: September 25, 2018
• Study Start: May 6, 2019
• Primary Completion: December 1, 2021
• Study Completion: May 22, 2025
• Last Updated: December 9, 2025
• Results First Posted: August 8, 2022

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

KE (2); ZA (3); TH (3)