Clinical trial NCT06967753: The Purpose of This Study is to Evaluate the Safety and Efficacy of a DTG + 3TC Based Dual Therapy as Switch Strategy Among ART-experienced TGW With HIV Receiving Suppresive Antiretroviral Therapy
Official title: Switch to Dolutegravir Plus Lamivudine Dual-therapy in Transgender Women Living With HIV on Virologically Suppressive Antiretroviral Therapy (TRANS-SWITCH)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: HIV
HIV-1
Keywords: dual therapy
dolutegravir
antiretroviral treatment
Lead sponsor: UBATEC
Sponsor class: OTHER
Collaborators: name: ViiV Healthcare
name: Hospital Fernandez
First posted: 2025-05-13
Enrollment: 50
Sex: MALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This single-arm, open label study is aimed to assess efficacy and safety of dolutegravir plus lamivudine as a switch strategy among TGW with HIV receiving suppresive antiretroviral therapy.

Detailed description: This is a phase IV, 48-week, prospective, open-label, and single arm study. Study population will include 50 TGW living with HIV on suppressive ART. Eligible participants will be switched to a 2DR base of DTG + 3TC once daily and follow-up period will be 48 weeks.

The study timeline will consist of:

* a selection period of up to 30 days,
* a 48-week treatment period,
* and a 4-week post-treatment follow-up period.

The aim of the study will be to explore the effectiveness, safety, and acceptability of DTG + 3TC dual therapy among TGW living with HIV.

Eligibility criteria: Inclusion Criteria:

1. 18 years or older at the time of signing the informed consent.
2. Self-identified as TGW.
3. Documented HIV-1 infection as per local standard: HIV-1 positive serology by at least two different serological tests (rapid test, ELISA, Western Blot) or a plasma HIV RNA viral ≥1,000 copies/mL.
4. ART-experienced participant on uninterrupted, stable, and suppressive triple ART for at least 3 months prior to screening, including: a) Acceptable stable ART regimens prior to Screening include 2 NRTIs plus i) INSTI ii) NNRTI or iii) Boosted PI. b) Any prior switch, defined as a change of a single drug or multiple drugs, must have occurred due to tolerability and/or safety concerns or access to medications, or convenience/simplification and must not have been done for suspected or established treatment failure. The following switches, if they are the only switches, would not be considered a change in regimen. a) A switch from a PI boosted with ritonavir (RTV) to the same PI boosted with cobicistat is allowed (and vice versa). b) A switch from 3TC to emtricitabine (FTC) (and vice versa). c) A switch from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) (and vice versa).
5. Documented evidence of at least two HIV-1 RNA pVL \<50 copies/mL in the last 12 months. HIV-1 RNA pVL corresponding to the screening visit may be accepted as second measurement.
6. Evidence of HIV-1 RNA pVL \<50 copies/mL at screening visit.
7. Do not have history of previous virological failure and/or evidence of resistance to DTG or 3TC as per protocol definition.
8. Participants must be able to understand and comply with protocol.
9. Written informed consent provided.

Exclusion Criteria:

1. History or presence of hypersensitivity to any of the study drugs or their components.
2. Evidence of known acute or chronic viral hepatitis B (positive Hepatitis B surface antigen \[HBsAg\]) or hepatitis C (detectable plasma HCV RNA viral load). Participants with chronic Hepatitis B (positive HBsAg) or Hepatitis C (positive plasma HCV RNA viral load) will be excluded. Individuals with evidence of previous Hepatitis B (positive for Hepatitis B core antibody \[HBcAc\] but negative HBsAg may be included on the trial. Individuals with positive anti-HCV antibodies but with non-detectable plasma HCV RNA (previously treated or spontaneously cleared HCV) may be included in the study.
3. Evidence of untreated syphilis infection (positive VDRL at screening without clear documentation of treatment). Participants who are at least 7 days post completed treatment are eligible.
4. Evidence of an active centers for disease control and prevention (CDC) Stage 3 disease, except cutaneous Kaposi's sarcoma not requiring systemic therapy. Historical or current CD4 cell counts less than 200 cells/millimeter are not exclusionary. Those individuals who are stable and receiving appropriate treatment for an HIV/AIDS-associated disease can be considered for the study.
5. Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected noninvasive cutaneous squamous cell carcinoma, or anal or penile intraepithelial neoplasia.
6. Participants with severe hepatic impairment (Class C) as determined by Child Pugh classification.
7. Any evidence of preexisting viral resistance based on the presence of any NRTI or INSTI major resistance associated mutation as per IAS-USA 2022 resistance panel in any historical resistance test result. 3TC resistance is considered in the presence of the M184V/I and/or K65R and/or Q151M mutations. DTG resistance is considered in the presence of the G118R, E138A/K/TG140A/C/R/S, Q148H/K/R, S153F/Y, N155H, or R263K mutations.
8. Participants who, as per the investigator's judgment, poses a significant suicidality risk. Recent history of suicidal behavior and/or suicidal ideation may be considered as evidence of serious suicide risk.
9. Receiving other medications with relevant interactions with DTG and/or 3TC.
10. Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of screening.
11. Treatment with any of the following agents within 28 days of screening: radiation therapy, cytotoxic chemotherapeutic agents, any systemic immune suppressant.
12. 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 the study drug.
13. Laboratory tests performed at the screening visit show any of the following results: a. Any verified Grade 4 laboratory abnormality. b. Hemoglobin \<9.0 g/dL c. Absolute neutrophil count \<750 cel/µL d. Platelet count \<80,000 cel/mm3 e. Creatinine clearance \<30 mL/min according to the Cockroft-Gault formula. f. Alanine aminotransferase (ALT) ≥5 times the upper limit of normal (ULN) or ALT ≥3 times ULN and bilirubin ≥1.5 times ULN (with \>35% direct bilirubin).
14. Any condition (including but not limited to the abuse of alcohol or drugs) which in the opinion of the investigator could compromise the participant's safety or adherence to the protocol.

Primary outcomes:
measure: Virological efficacy
timeFrame: 48 weeks
Secondary outcomes:
measure: Virological efficacy
timeFrame: 48 weeks
measure: Virological efficacy
timeFrame: 24 weeks
measure: Changes in CD4+ count
timeFrame: 24 and 48 weeks
measure: Safety - Adverse Events (including Serious Adverse Events and Adverse Events Leading to Discontinuation)
timeFrame: 48 weeks
measure: Changes in lipid profile measurements
timeFrame: 24 and 48 weeks
measure: Changes in Kidney Function measurements
timeFrame: 24 and 48 weeks
measure: Changes in Body Weight
timeFrame: 24 and 48 weeks
measure: Changes in Bone Mineral Density
timeFrame: 48 weeks
measure: Emerging resistance to study drugs
timeFrame: 48 weeks
measure: Quality of LIfe
timeFrame: Weeks 4, 24 and 48
measure: Treatment acceptance
timeFrame: Weeks 4, 24 and 48
measure: Treatment Adherence
timeFrame: Weeks 4, 12, 24, 36 and 48.
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: Hospital General de Agudos Dr. Juan A. Fernández, Infectious Diseases Division
state: Caba
Study officials:
affiliation: Hospital Fernández, Infectious Diseases Division
name: Martín Jaume, MD
role: PRINCIPAL_INVESTIGATOR
References: