Resumen

Título del protocolo: «Eficacia y seguridad de doravirina en el inicio rápido de terapia antirretroviral de alta actividad (TARGA) en pacientes con VIH-1 positivo sin tratamiento previo.»

Descripción detallada

Número de protocolo: FH-96 Objetivo primario: Evaluar la actividad antiviral de DOR/3TC/TDF a la semana 48 en VIH. Objetivos secundarios: 1\. Evaluar la actividad antiviral de DOR/3TC/TDF a \< 200 copias/mL a la semana 48, mediante el análisis por intención de tratar (análisis FDA snapshot) para la población expuesta (ITT-E). 2. Evaluar la actividad antiviral de DOR/3TC/TDF a la semana 48 mediante un análisis observado (que incluye únicamente a los pacientes con datos virológicos disponibles). 3\. Evaluar la actividad antiviral de DOR/3TC/TDF en el subgrupo de participantes con mutaciones de ITINN basales que no confieren resistencia a doravirina (según la lista de mutaciones definida en los criterios de exclusión), calculando la proporción de pacientes con carga viral \<200 copias/mL y \<50 copias/mL a la semana 48. 4\. Evaluar la actividad antiviral de DOR/3TC/TDF a \<200 copias/mL y \<50 copias/mL a la semana 24. 5\. Evaluar la seguridad y tolerabilidad de DOR/3TC/TDF. 6. Evaluar la actividad antiviral de DOR/3TC/TDF a la semana 48 en pacientes con carga viral basal \>100.000 copias/mL. 7\. Respuesta inmunológica: evaluar la recuperación inmunológica (recuentos de células T CD4, CD8 y cociente CD4/CD8) a las semanas 24 y 48. 8\. Evaluar el desarrollo de resistencia al VIH-1 en pacientes que experimenten fracaso virológico durante el tratamiento con DOR/3TC/TDF. 9\. Evaluar los cambios en el peso, el IMC y el perfil lipídico (colesterol total, HDL, LDL y triglicéridos) a las semanas 24 y 48. Población del estudio: Los sujetos serán pacientes con infección por VIH-1 sin experiencia con ARV (naïve) dentro de los 30 días posteriores al diagnóstico, dispuestos a iniciar terapia ARV en un contexto de inicio rápido, con edad ≥ 18 años, que cumplan todos los criterios de inclusión y no cumplan ninguno de los criterios de exclusión. Diseño del estudio: Estudio de fase IV, multicéntrico, no aleatorizado, de un solo brazo y etiqueta abierta, que describe la eficacia antiviral, la seguridad y la tolerabilidad de la terapia DOR/3TC/TDF como tratamiento de inicio rápido en sujetos con infección por VIH-1 que no han recibido tratamiento previo. Regímenes: Doravirina 100 mg; Lamivudina 300 mg; Tenofovir disoproxilo 245 mg. Trece frascos. (Nombre comercial: DELSTRIGO - MSD). Duración: 48 semanas. Tamaño de muestra: 100 sujetos

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 90 YearsSexo: ALL

Criterios de inclusión

Subject has to voluntarily signed and dated an informed consent form, approved by an institutional ethics committee.
≥18 years of age.
Not previously exposed to ARV (naïve). Subject may have received oral PrEP and PEP within the last 6 months and injectable PrEP and PEP within the last year.
Have a received an HIV diagnosis within 30 days prior to selection. Defined as: Having confirmed HIV-1 infection. HIV-1 positive result is considered if the HIV1 RNA in plasma is ≥ 1000 copies/mL or two HIV antibody tests (using two different tests) are positive.
NOTE: Participants may be included without knowing their baseline viral load. If baseline viral load results are less than 1000 copies/mL, the volunteer's participation will be suspended and they will be considered to have failed the screening test. A viral load brought by the subject may be considered if it was performed within the last 30 days prior to the SCR visit.
CD4+ T-cell count: No limit.
Subjects able to meet the protocol requirements.

Criterios de exclusión

History of hypersensitivity to doravirine, tenofovir, or lamivudine.
Severe hepatic impairment (Child-Pugh C).
Active HCV infection requiring specific treatment during study participation at the time of eligibility assessment. If HCV is diagnosed during the study and the participant requires treatment, the decision on whether to continue in the study will be at the investigator's discretion.
A woman may be eligible to enter and participate in the study if she is not pregnant (confirmed by a negative urine pregnancy test at the time of screening/baseline). If the baseline visit is scheduled on a different day than the SCR, the urine pregnancy test will be repeated) or breastfeeding and if at least one of the following conditions applies:
Women without reproductive capacity, defined as premenopausal women with tubal ligation or hysterectomy, or documented bilateral oophorectomy; or as postmenopausal women with 12 months of spontaneous amenorrhea, and women ≥ 45 years of age without hormone replacement therapy.
Women with reproductive capacity who agree to adopt one of the contraceptive options in Appendix 2 for at least 30 days after the last dose of study medication and/or completion of the follow-up visit.
The chosen contraceptive method must be used consistently, according to the approved product label. All study participants must be advised on safer sex practices, including the use of effective barrier methods, and the choice of effective contraceptive method must be documented in the eCRF (Electronic Case Report Form).
The subject's general health status, in the investigator's oIPnion, interferes with the requirements of the study.
Has a diagnosis of an active opportunistic infection defining AIDS or a malignant neoplasm within 30 days prior to evaluation (except Kaposi's sarcoma with fewer than 10 skin lesions).
Is participating or has participated in a clinical study in the last 6 months.
Creatinine clearance (CrCl) ≤50 mL/min according to the Cockcroft-Gault equation.
Any verified Grade 4 abnormality (except liIPds: HDL, LDL, total cholesterol, triglycerides).
History or presence of allergy to study drugs or their components, or to drugs in their class.
Subjects taking any medication during the study, including over-the-counter medications and herbal preparations, without the approval of the study physician.
Mutations resistant to doravirine, 3TC, or TDF, according to the list described below:
DOR mutations (INNTI):
Doravirine (INNTI) Primary: the presence of one or more ART-resistant mutations will be grounds for exclusion.
Mutations: V106A/M, F227C/V, L234I, Y188L, Y318F, M230I/L. Secondary: the presence of one or more RAMs will be grounds for exclusion. Mutations: A98G, V108I, G190E, H221Y, P225H, F227L, P236L. Others: the presence of five or more RAMs will be grounds for exclusion. Mutations: V90I, L100I, K101E/H/P, K103N/R/S, V106I, I135T, Y181C/I/V, E138A/G/K/Q/R, V170F/T, G190A/Q/S, Y188C/H, F227I, V245E, K311R.
NRTI (TDF) Relevant mutations: Presence of one or more RAM Mutations: K65R, insertion 69, K70R/E, Q151M,
NRTI (3TC) Relevant mutation Presence of IM184V

Intervenciones

drug

Doravirine / lamivudine/ Tenofovir Disoproxil Oral Tablet

Pharmaceutical form: Oral tablets Unit dose concentration/dose level(s): 100/300/245 mg Administration instructions: Take one tablet once a day

Ubicaciones

Fundacion IDEAA -Infectologia de atencion ambulatoria

Ciudad Autonoma de Buenos Aire, Buenos Aires, Argentina

Ezequiel Cordova, MD · dr_ecordova@hotmail.com · 011 49017133

Fundacion Huesped

Buenos Aires, Argentina

Patrocinadores

PrincipalFundación Huésped

ColaboradorMSD Pharmaceuticals LLC

ColaboradorFundacion IDEAA

Contactos

Pedro E Cahn, MD

CONTACT

pedro.cahn@huesped.org.ar 1121209999

María I Figueroa, MD

CONTACT

maria.figueroa@huesped.org.ar 1121209999