Switch to Dolutegravir Plus Lamivudine Dual-Therapy in Transgender Women Living With HIV on Virologically Suppressive Antiretroviral Therapy (TRANS-SWITCH)

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.

Inclusion criteria

• 18 years or older at the time of signing the informed consent.
• Self-identified as TGW.
• 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.
• 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).
• 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.
• Evidence of HIV-1 RNA pVL <50 copies/mL at screening visit.
• Do not have history of previous virological failure and/or evidence of resistance to DTG or 3TC as per protocol definition.
• Participants must be able to understand and comply with protocol.
• Written informed consent provided.

Exclusion criteria

• History or presence of hypersensitivity to any of the study drugs or their components.
• 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.
• 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.
• 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.
• Ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected noninvasive cutaneous squamous cell carcinoma, or anal or penile intraepithelial neoplasia.
• Participants with severe hepatic impairment (Class C) as determined by Child Pugh classification.
• 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.
• 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.
• Receiving other medications with relevant interactions with DTG and/or 3TC.
• Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of screening.
• Treatment with any of the following agents within 28 days of screening: radiation therapy, cytotoxic chemotherapeutic agents, any systemic immune suppressant.
• 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.
• 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).
• 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.