Resumen

Este estudio de un solo brazo y abierto tiene como objetivo evaluar la eficacia y seguridad de dolutegravir más lamivudina como estrategia de cambio en mujeres transgénero (MT) con VIH que reciben tratamiento antirretroviral (TAR) supresor.

Descripción detallada

Este es un estudio fase IV, de 48 semanas, prospectivo, abierto y de un solo brazo. La población del estudio incluirá 50 MT que viven con VIH bajo TAR supresor. Los participantes elegibles serán cambiados a una base de terapia dual (2DR) con DTG + 3TC una vez al día, y el período de seguimiento será de 48 semanas. El cronograma del estudio constará de: * un período de selección de hasta 30 días, * un período de tratamiento de 48 semanas, * y un período de seguimiento postratamiento de 4 semanas. El objetivo del estudio será explorar la efectividad, seguridad y aceptabilidad de la terapia dual DTG + 3TC en MT que viven con VIH.

Elegibilidad

Edad mínima: 18 YearsSexo: MALE

Criterios de inclusión

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.

Criterios de exclusión

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.

Intervenciones

drug

Dolutegravir 50 MG plus lamivudine 300 MG； Dolutegravir/lamivudine (50 MG/300 MG)

Enrolled participants will be switched to a dual therapy regimen consisting of 50-mg DTG plus 300-mg 3TC tablet (as a single pill fixed dose combination) orally administered once daily with or without food. No dose reductions, modifications in dosage, or changes in the frequency of dosing will be allowed in this study.

Cambio a terapia dual con dolutegravir más lamivudina en mujeres transgénero que viven con VIH bajo tratamiento antirretroviral con supresión virológica (TRANS-SWITCH)

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Dolutegravir 50 MG plus lamivudine 300 MG； Dolutegravir/lamivudine (50 MG/300 MG)

Ubicaciones

Hospital General de Agudos Dr. Juan A. Fernández, Infectious Diseases Division

Patrocinadores

Contactos

Martín Jaume, MD

José AE Barletta, MD