Safety and Efficacy of Fixed Dose Combination Dolutegravir/Abacavir/Lamivudine FDC Initiated During Acute HIV Infection

NCT02384395 | Completed Results

• 1 other identifier: 14-0549
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

This is a multicenter, single arm, 96-week open-label study of the safety and virologic efficacy of fixed dose combination Dolutegravir/Lamivudine/Abacavir (DTG/3TC/ABC FDC) initiated during acute HIV infection (AHI).

Conditions

HIV; Acute HIV Infection

Keywords

Dolutegravir; Abacavir; Lamivudine; acute HIV infection; human leukocyte antigen; latent HIV reservoir; integrase-based regimen; viremia; antiretroviral therapy; fixed dose combination

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Viral Load Measurement <200 Copies/mL at Week 24

  Total number of participants on study at Week 24 with an HIV-1 RNA level less than 200 copies/mL

  Week 24

Secondary Outcomes (3)

• Number of Participants With Grade 3 or Higher Adverse Event (AE)

  Baseline through Week 96

• Proportion of Treated Participants With HIV-1 RNA to <50 Copies/mL at Week 48

  Week 48

• Median Change HIV-1 RNA Level Among Participants Completing Week 24 Visit

  Baseline, Week 24

Study Arms (1)

DTG/3TC/ABC FDC

EXPERIMENTAL

Dolutegravir (DTG 50 mg), abacavir sulfate (ABC 600 mg) and lamivudine (3TC 300 mg) formulated in a single tablet fixed dose combination (FDC) (DTG/ABC/3TC, GSK2619619), administered orally, once daily

Drug: Dolutegravir 50 mg; Drug: Lamivudine 300 mg; Drug: Abacavir 600 mg

Interventions

Dolutegravir 50 mg DRUG

Initial therapy for AHI

Also known as: DTG, Tivicay

DTG/3TC/ABC FDC

Lamivudine 300 mg DRUG

Initial therapy for AHI

Also known as: 3TC, Epivir

DTG/3TC/ABC FDC

Abacavir 600 mg DRUG

Initial therapy for AHI

Also known as: ABC, Ziagen

DTG/3TC/ABC FDC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documentation of Acute HIV infection at or within 30 days of study entry.
• Men and women age ≥18 years.
• ART naive, defined as ≤14 days of antiretroviral treatment at any time prior to entry. The only exceptions are:
• Pre-exposure prophylaxis (PrEP) and documented as HIV-1 negative at least 1 month prior to AHI diagnosis during PrEP, and
• Post-exposure prophylaxis (PEP) provided the participant was documented as HIV-1 negative at least 3-6 months following completion of PEP treatment.
• Lab values obtained within 30 days prior to study entry:
• Absolute neutrophil count \>500/mm\^3
• Hemoglobin \> 8.5 g/dL for men and \> 8.0 g/dL for women
• Platelet count \>50,000/mm\^3
• Lipase ≤ 3 X upper limit of normal (ULN), single repeat test is allowed to determine eligibility
• Calculated creatinine clearance (CrCl, Cockcroft-Gault formula) ≥ 50 mL/min:
• CrCl = (140-age) x body weight (kg) (x 0.85 if female) Serum creatinine \[mg/dL\] x (72)
• Testing for HBsAg is pending. Note: Participants who test positive for HBsAg will be terminated from the study prior to starting study treatment.
• Testing for HLA-B57 and/or HLA-B\*5701 is pending. Note: Participants who test positive for HLA-B\*5701 will be terminated from the study prior to starting study treatment.
• A female is eligible to enter and participate in the study if she:

You may not qualify if:

• Alanine Transaminase (ALT) ≥ 5 times Upper Limit of Normal (≥5xULN)
• Aspartate Aminotransferase (AST) ≥ 3x ULN
• Bilirubin ≥1.5x ULN (with \>35% direct bilirubin)
• Weight \<40 kg
• Women who are breast-feeding.
• Women with a positive pregnancy test on enrollment or prior to study drug administration.
• Women and men of child bearing potential unwilling to agree to use an effective methods of contraception required by the study.
• History or presence of allergy to the study drugs or their components.
• Requires or is anticipated to require any of the prohibited concomitant therapy: barbiturates, dofetilide, fampridine (dalfampridine), modafinil, oxcarbazepine, pioglitazone, pilsicainide, pimozide, rifampin, rifapentine, phenytoin, phenobarbital, carbamazepine, and St. John's wort.
• Dofetilide, fampridine, and pilsicainide are prohibited, as DTG may inhibit its renal tubular secretion resulting in increased dofetilide concentrations and potential for toxicity.
• Unable to discontinue any current medications that are excluded during study treatment.
• Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), radiation therapy, HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 30 days prior to study entry.
• Prednisone at a daily dose of 10 mg or less (physiologic replacement dose) is permitted.
• Treatment with radiation therapy or cytotoxic chemotherapeutics agents within 28 days prior to screening or has an anticipated need for these agents during the study.
• Administration of an HIV-1 immunotherapeutic vaccine within 90 days prior to screening.

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• ViiV Healthcare: collaborator

Study Sites (2)

University of North Carolina

Chapel Hill, North Carolina, 27599, United States

Location

Duke University Health System

Durham, North Carolina, 27710, United States

Location

Related Publications (50)

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• D:A:D Study Group; Sabin CA, Worm SW, Weber R, Reiss P, El-Sadr W, Dabis F, De Wit S, Law M, D'Arminio Monforte A, Friis-Moller N, Kirk O, Pradier C, Weller I, Phillips AN, Lundgren JD. Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D:A:D study: a multi-cohort collaboration. Lancet. 2008 Apr 26;371(9622):1417-26. doi: 10.1016/S0140-6736(08)60423-7. Epub 2008 Apr 2.

  PMID: 18387667 BACKGROUND

• Costagliola D, Lang S, Mary-Krause M, Boccara F. Abacavir and cardiovascular risk: reviewing the evidence. Curr HIV/AIDS Rep. 2010 Aug;7(3):127-33. doi: 10.1007/s11904-010-0047-3.

  PMID: 20521126 BACKGROUND

Related Links

• University of North Carolina website

MeSH Terms

Conditions

Viremia

Interventions

dolutegravir; Lamivudine; abacavir

Condition Hierarchy (Ancestors)

Virus Diseases; Infections; Sepsis; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides

Results Point of Contact

• Title: Cynthia Gay, MD, MPH
• Organization: University of North Carolina at Chapel Hill

cynthia_gay@med.unc.edu

919-966-6712

Study Officials

• Cindy Gay, MD, MPH

  University of North Carolina

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 4, 2015
• First Posted: March 10, 2015
• Study Start: September 1, 2015
• Primary Completion: March 6, 2020
• Study Completion: September 17, 2021
• Last Updated: November 22, 2021
• Results First Posted: November 22, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)