Evaluating Inflammatory and Immunological Changes of HIV-positive Patients Switching to DTG Dual Regimen Compared to Those Switching to a Triple Drugs Regimen (B/F/TAF)

Long-term side effects of antiretrovirals (ART) have led to the introduction in clinical practice of NRTI-sparing regimens as double- or mono- therapy and their use is now recommended in specific populations by International Guidelines. Indeed, based on the monitoring of surrogate markers of ART efficacy, most of these unconventional regimens, when used in switch studies, have shown to have a non-inferior virological efficacy and a good CD4 recovery compared to standard triple drug-based therapy.

At present, the best marker to evaluate the risk of developing of non-AIDS related events has not been determined. Interestingly, the analysis of the data of the investigator's and others cohorts have shown that, in contrast with recent data from ART-CC collaboration, a low CD4/CD8 ratio is a predictor of non-AIDS related events independently from CD4 cell count, while other studies have shown an association of this marker with non-AIDS defining cancers or, more recently, with pulmonary emphysema. Aim of the present study is to compare CD8 and CD4/CD8 slopes in patients switching with an undetectable viral load to the 2 regimens which will be more frequently used in clinical practice: i.e B/F/TAF and dolutegravir + lamivudine. Indeed, B/F/TAF is already a recommended regimen in all guidelines while dolutegravir + lamivudine is widely used in clinical practice.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Bictegravir 50 MG / Emtricitabine 200 MG / Tenofovir Alafenamide 25 MG [Biktarvy]; Drug: dolutegravir 50 mg / lamivudine 300 mg

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 4

Contacts and Locations

Study Locations

• Italy
  • Modena, Italy, 41124
    • University Hospital of Modena- Infetious Diseases Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age = 18 years
2. The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
3. Patients infected by HIV-1
4. Patients under the first-line cART regimen with three antiretrovirals
5. HIV-RNA <=50 copies/mL for at least 12 months
6. No previous virological failures/blips

7. A female subject is eligible to enter the study if it is confirmed that she is:

   • Not pregnant or nursing
   • Of non-childbearing potential (e.g., women who have had a hysterectomy, have had both ovaries removed or medically documented ovarian failure, or are postmenopausal women >54 years of age with cessation for =12 months of previously occurring menses)
   • Of chilbearing potential and agrees to utilize highly effective contraception methods or be non-heterosexually active or practice sexual abstinence from screening throughout the duration of study treatment and for 30 days following discontinuation of study drugs
   • Female subjects who utilize hormonal contraceptive as one of their birth control methods must have used the same method for at least three months prior to study dosing
8. Male subjects must agree to utilize a highly effective method of contraception (as defined in Appendix 5) during heterosexual intercourse or be non-heterosexually active, or practice sexual abstinence from first dose throughout the study period and for 30 days following the last study drug dose.
9. Male subjects must agree to refrain from sperm donation from first dose until at least 30 days after the last study drug dose.

Exclusion Criteria:

1. Patients with chronic hepatitis B
2. Pregnant or breastfeeding women
3. Current alcohol or substance use judged by the Investigator to potentially interfere with subject study compliance
4. Known hypersensitivity to B/F/TAF FDC tablets, DTG and 3TC, their metabolites, or formulation excipient

5. Subjects receiving ongoing therapy with any of the following medications in the table below, including drugs not to be used with B, F, TAF, DTG and 3TC.

   Administration of any of the previous medications must be discontinued at least 30 days prior to the Day 1 visit and for the duration of the study

6. Documented resistance to any of the study drugs
7. Active, serious infection (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Day 1.
8. Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with protocol requirements. -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: A; B/F/TAF	Drug: Bictegravir 50 MG / Emtricitabine 200 MG / Tenofovir Alafenamide 25 MG [Biktarvy]; Biktarvy OD
Active Comparator: B; DTG+3TC	Drug: dolutegravir 50 mg / lamivudine 300 mg; DTG +3TC (Dovato OD)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
CD8 slope and consequent CD4/CD8 ratio difference between the 2 arms	week48

Collaborators and Investigators

• Sponsor: Cristina Mussini

Publications and helpful links

General Publications

• Cossarizza A, Cozzi-Lepri A, Mattioli M, Paolini A, Neroni A, De Biasi S, Tartaro DL, Borella R, Fidanza L, Gibellini L, Beghetto B, Roncaglia E, Nardini G, Milic J, Menozzi M, Cuomo G, Digaetano M, Orlando G, Borghi V, Guaraldi G, Mussini C. Evaluating immunological and inflammatory changes of treatment-experienced people living with HIV switching from first-line triple cART regimens to DTG/3TC vs. B/F/TAF: the DEBATE trial. Front Immunol. 2023 Oct 16;14:1279390. doi: 10.3389/fimmu.2023.1279390. eCollection 2023.

Study record dates

Study Major Dates

• Study Start (Actual): January 23, 2020
• Primary Completion (Actual): January 23, 2020
• Study Completion (Actual): February 28, 2022

Study Registration Dates

• First Submitted: August 2, 2019
• First Submitted That Met QC Criteria: August 12, 2019
• First Posted (Actual): August 13, 2019

Study Record Updates

• Last Update Posted (Actual): May 1, 2026
• Last Update Submitted That Met QC Criteria: April 30, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; HIV Infections; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Deoxyribonucleosides; Dideoxynucleosides; Zalcitabine; Emtricitabine; Lamivudine; tenofovir alafenamide; dolutegravir; bictegravir; bictegravir, emtricitabine, tenofovir alafenamide, drug combination
• Other Study ID Numbers: DEBATE; 2018-003458-26 (EudraCT Number)

Drug and device information, study documents

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