Dolutegravir-Lamivudine for naïve HIV-Infected Patients With ≤200 CD4/mm3 (DOLCE)

Protocol Title: DOLCE: Dolutegravir-Lamivudine for naïve HIV-Infected Patients with ≤200 CD4/mm3

Protocol Number: FH-57

Study Objectives: To assess the antiviral activity at week 48 of DTG+3TC among naïve HIV patients with a CD4 count ≤200 cells /mm3.

Study Overview

• Status: Completed
• Conditions: HIV-1-infection
• Intervention / Treatment: Drug: Intervention Arm: dolutegravir/lamivudine; Drug: Comparator ARM: TDF/XTC plus Dolutegravir (XTC stand for lamivudine OR emtricitabine)

Detailed Description

Primary endpoint: Proportion of patients with viral load < 50 copies/mL at week 48 using the ITT-exposed analysis (FDA snapshot) for the intent-to-treat exposed (ITT-E) population.

Secondary Objectives:

• To assess the antiviral activity of DTG+3TC and DTG+TDF/XTC at week 24
• To evaluate the safety and tolerability of DTG+3TC and DTG+TDF/XTC over time
• To assess the antiviral activity of DTG+3TC and DTG+TDF/XTC at week 48 in patients with baseline viral load >100,000 c/mL
• To evaluate immunological activity (CD4+ lymphocyte [CD4 counts]) at Week 24 and Week 48
• To assess the development of HIV-1 resistance in patients with virologic failure or viral rebound treated with DTG+3TC or DTG+TDF/XTC
• To evaluate the incidence of disease progression (HIV-associated conditions, AIDS and death) of DTG + 3TC and DTG + TDF/XTC over time.

Secondary endpoints:

• Proportion of patients treated with DTG+3TC and DTG+TDF/XTC with HIV-1 levels of less than 50 copies/mL at week 24
• Frequency, type and severity of adverse events and laboratory abnormalities and proportion of patients who discontinue DTG+3TC or DTG+TDF/XTC due to adverse events or death
• Proportion of patients with baseline HIV-1 RNA >100,000 c/mL that achieve virological suppression at week 48 weeks,
• Changes in CD4 count, CD8 count and CD4/CD8 ratio between baseline and 48 weeks
• Number and type of resistance mutations in case of virologic failure (defined as a confirmed viral above 200 copies/mL after week 24 copies/mL or viral rebound at any timepoint)
• Incidence of IRIS and disease progression (HIV associated conditions, AIDS and death).

Tertiary objectives:

● TDF/XTCTo explore change in health-related quality-of-life for subjects treated with DTG plus 3TC and DTG + TDF/XTC

Tertiary endpoints:

● Change from Baseline in health-related quality of life using EQ-5D-5L and PHQ9 at Weeks 24, and 48

Patient Population:

HIV-1-infected subjects aged >18 years who are naïve to antiretroviral therapy with ≤200 CD4 cell/mm3

Study Design:

Prospective, Phase IV, randomized, multicenter, parallel group study design

Regimens:

Dolutegravir 50 mg /lamivudine 300 mg QD FDC. Dolutegravir 50 mg QD plus tenofovir 300 mg/emtricitabine 200mg or plus tenofovir 300 mg/ lamivudine 300 mg.

Duration: 48 weeks

Sample size:230 subjects

• Study Type: Interventional
• Enrollment (Actual): 265
• Phase: Phase 4

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1425AGP
    • Hospital de Agudos J.A.Fernandez
  • Buenos Aires
    • Ciudad Autonoma de Buenos Aire, Buenos Aires, Argentina, 1202
      • Fundación Huésped
    • Ciudad Autonoma de Buenos Aire, Buenos Aires, Argentina, C1155 AHD
      • Hospital General de Agudos Dr. Cosme Argerich
    • Ciudad Autónoma de Buenos Aires, Buenos Aires, Argentina, 1282
      • Hospital de Infecciosas Francisco Javier Muñiz
  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2000
      • Instituto CAICI
• Brazil
  • São Paulo, Brazil, 04121-000
    • Centro de Treinamento e Referência DST/AIDS
  • Bahia
    • Salvador, Bahia, Brazil, 40110-160
      • Fundação Bahiana de Infectologia
  • Pernambuco
    • Recife, Pernambuco, Brazil, 50100-130
      • HUOC - Hospital Universitário Oswal do Cruz - Universidade de Pernambuco
  • RJ
    • Nova Iguaçu, RJ, Brazil, 26030-380
      • Hospital Geral de Nova Iguaçu
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-903
      • Hospital de Clínicas de Porto Alegre
  • São Paulo
    • Pacaembu, São Paulo, Brazil, 01246-900
      • Centro de Pesquisa: Instituto de Infectologia Emílio Ribas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subject has voluntarily signed and dated an informed consent form, approved by an Institutional Review Board (IRB) / Independent Ethics Committee (IEC), after the nature of the study has been explained and the subject has had the opportunity to ask questions.
2. Documented HIV-1 infection defined as a positive rapid test or ELISA plus a plasma HIV-1 RNA (>1,000 copies/mL) or a positive western blot. A previous result performed on the last 30 days can be used.
3. ≥18 years of age
4. Naïve to ARV therapies (defined as ≤ 10 days of prior therapy with any antiretroviral therapy following an HIV diagnosis). Previous use of PrEP or PEP is allowed if there is documented HIV seronegativity between the last prophylactic dose and the date of HIV diagnosis.
5. HIV RNA at screening visit > or = 1,000 copies/mL. A previous result performed on the last 30 days can be used.
6. CD4 at screening < or = 200 cells/mL A previous result performed on the last 30 days can be used.
7. Subjects can comply with protocol requirements.
8. Subject agrees not to take any medication during the study, including over-the-counter medicines or herbal preparations, without the approval of the trial physician.
9. Subject's general medical condition, in the investigator's opinion, does not interfere with assessments and completion of the study.

10. A female may be eligible to enter and participate in the study if she is not pregnant (as confirmed by serum pregnancy test negative at screening, and a urine negative test at baseline), not lactating and at least one of the following condition applies:

    1. Women with non-reproductive potential, defined as pre-menospausal females with documented tubal ligation or hysterectomy, or bilateral oophorectomy; or as post-menospausal women defined as 12 months of spontaneous amenorrhea, and ≥45 years of age in women without hormonal replacement therapy.
    2. Women with reproductive potential and agrees to follow one of the contraceptive options listed in the Appendix 3 from at least 15 days prior to the first dose of medication and until at least 30 days after the last dose of study medication and completion of the follow-up visit.

Any contraception method must be used consistently, in accordance with the approved product label. All subjects participating in the study should be counselled on safer sexual practices including the use of effective barrier methods and the choice of effective contraceptive method should be documented in the eCRF.

Exclusion Criteria:

1. Women who are pregnant or breastfeeding, or women who plan to become pregnant in the next year.
2. Subjects testing positive for Hepatitis B surface antigen (+HBsAg) at screening, or anticipated need for Hepatitis C virus (HCV) therapy with drugs with potential drug-drug interaction during the study.
3. Subjects with severe hepatic impairment (Child-Pugh class C), or unstable liver disease (ascites, encephalopathy, coagulopathy, or oesophageal or gastric varices) or cirrhosis.
4. Opportunistic infections that impede to start ART immediately (specifically tuberculosis, meningeal tuberculosis or cryptococcosis within the first month of specific treatment). Subjects with other suspected or confirmed active opportunistic infections and subjects with cryptococcal disease after the initial period can be included if she/he can follow the protocol and if her/his participation could benefit the subject. A clear documentation of these aspects must to be done in the clinical chart of the participant.
5. Subjects who in the investigator's judgment, pose a significant suicidality risk.
6. History or presence of allergy to the study drugs or their components or drugs of their class
7. Treatment with any of the following agents within 28 days of screening: radiation therapy; cytotoxic chemotherapeutic agents; any immunomodulators that alter immune responses; or treatment with an HIV-1 immunotherapeutic vaccine within 90 days of screening; or exposure to an experimental drug or experimental vaccine within either 28 days, 5 half-lives of the test agent, or twice the duration of the biological effect of the test agent, whichever is longer, prior to the first dose of investigational product.
8. Any previous evidence of resistance to dolutegravir (defined as the presence of G118R, Q148 H/K/R or R263K), to lamivudine (presence of the mutation M184V) or resistance to tenofovir (mutation K65R or more than 3 TAMs) with a Sanger sequence method or using next-generation sequencing (NGS) at a frequency >15%. If the subject does not have a previous resistance test, samples will be taken at the screening visit and the subject can be randomized and start the study. while awaiting the results (see section 4.8).
9. Any verified Grade 4 abnormality.
10. Alanine aminotransferase (ALT) ≥ 5 times the upper limit of normal (ULN), or ALT ≥ 3xULN and bilirubin ≥ 1.5xULN (with >35% direct bilirubin).
11. Creatinine clearance of <50mL/min via Cockroft-Gault method.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Experimental : Dolutegravir plus Lamivudine; DOVATO: Dolutegravir 50mg/lamivudine 300 mg, FDC, 1 coformulated tablet QD	Drug: Intervention Arm: dolutegravir/lamivudine; 1 pill QD; Other Names: Dovato
Active Comparator: active comparator : TDF/XTC plus Dolutegravir (XTC stands for lamivudine OR emtricitabine); Unit Dose: TDF/FTC 300/200 mg, 1 coformulated tablet QD (FDC) plus Dolutegravir 50 mg, 1 tablet QD OR; TDF/3TC 300/300 mg, 1 coformulated tablet QD (FDC) plus Dolutegravir 50 mg, 1 tablet QD	Drug: Comparator ARM: TDF/XTC plus Dolutegravir (XTC stand for lamivudine OR emtricitabine); 1 pill of each QD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antiviral Activity at Week 48 of DTG+3TC Among ART-naïve HIV Patients With a CD4 Count ≤200 Cells/mm3.	Percentage of patients with viral load < 50 copies/mL at week 48 using the ITT-exposed analysis (FDA snapshot) for the intent-to-treat exposed (ITT-E) population.	Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antiviral Activity of DTG+3TC and DTG+TDF/XTC (TDF/FTC or TDF/3TC) at Week 24	Percentage of patients treated with DTG+3TC and DTG+TDF/XTC with HIV-1 levels of less than 50 copies/mL at week 24	Week 24
Safety and Tolerability of DTG+3TC and DTG+TDF/XTC Over Time	Percentage of patients who discontinue treatment due to adverse events or death	week 48
Antiviral Activity of DTG+3TC and DTG+TDF/XTC at Week 48 in Patients With Baseline Viral Load >100,000 c/mL	Percentage of patients with baseline viral load >100,000 c/mL that reach HIV-1 levels of less than 50 copies/mL at week 48	Week 48
Changes in Lymphocytes Subsets Between Baseline and 48 Weeks	Changes in lymphocytes CD4 cells count per mL	Week 48
Development of HIV-1 Resistance in Patients With Virologic Failure or Viral Rebound Whilst Being Treated With DTG+3TC or DTG+TDF/XTC	Number and type of resistance mutations in case of virologic failure (defined as a confirmed viral above 200 copies/mL on or after week 24 or confirmed viral rebound at any timepoint)	week 48
Incidence of IRIS or Disease Progression (HIV Associated Conditions, AIDS and Death).	Evaluation of disease progression incidence (HIV-associated conditions, AIDS and death) with DTG+3TC and DTG + TDF/XTC treatment over time	week 48

Collaborators and Investigators

• Sponsor: Fundación Huésped
• Collaborators: ViiV Healthcare; Federal University of Bahia
• Investigators: Principal Investigator: Maria Ines Figueroa, PI, Fundación Huésped

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2021
• Primary Completion (Actual): May 7, 2024
• Study Completion (Actual): May 7, 2024

Study Registration Dates

• First Submitted: April 26, 2021
• First Submitted That Met QC Criteria: May 5, 2021
• First Posted (Actual): May 10, 2021

Study Record Updates

• Last Update Posted (Actual): July 30, 2025
• Last Update Submitted That Met QC Criteria: July 29, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: antiretroviral naive triple therapy. Dolutegravir-Lamivudine; dual-therapy
• Additional Relevant MeSH Terms: Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Nucleic Acid Synthesis Inhibitors; Antiviral Agents; Reverse Transcriptase Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Emtricitabine; Dolutegravir; Lamivudine
• Other Study ID Numbers: FH 57

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD available upon request. The request should be supported with a hypothesis-driven project, that should include analysis plan
• IPD Sharing Time Frame: 3 month after last patient last visit
• IPD Sharing Access Criteria: By request
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No