Latency and Early Neonatal Provision of Antiretroviral Drugs Clinical Trial (LEOPARD)
The investigators propose a non-randomized clinical trial of 60 HIV-infected infants identified within 48 hours of birth and their mothers to investigate the consequences of very early ART on the establishment and maintenance of the viral reservoir.
The first phase (early ART initiation within 48 hours of birth) will examine the trajectory i.e. changes over time of the viral reservoir and detection of HIV-specific antibody responses in infants testing HIV-positive within 48 hours of birth and initiating early ART.
Secondary pathogenesis aims will test whether markers of neonatal immune quiescence are associated with the extent of seeding and rate of decline of the viral reservoir when ART is started at a young age and investigate whether markers in infant stool samples can be used as a non-invasive method of defining relevant immune and HIV-specific parameters associated with viral reservoir size.
The investigators hypothesize that developmental characteristics of newborn immunity may make this period the optimal time to begin ART and influence the seeding of the viral reservoir.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 4
Contactos y Ubicaciones
Ubicaciones de estudio
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Gauteng
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Johannesburg, Gauteng, Sudáfrica
- Rahima Moosa Mother and Child Hospital
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
- Point of care (POC) or laboratory-based test positive on a sample collected within 48 hours of birth.
- Mother willing and able to provide informed consent.
Exclusion Criteria:
- Expressed intention to leave the Johannesburg area permanently.
- Co-morbidities, birth defects or other conditions which in the opinion of the clinical team have a greater than 50% risk of mortality in the first days of life.
- Co-morbidities or conditions which in the opinion of the clinical team advise against initiation of ART within the first 48 hours of life.
- Active (uncontrolled) maternal psychiatric illness.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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Experimental: Early ART
All infants enrolled in the trial, regardless of maternal PMTCT regimen, will be initiated on a triple ARV regimen consisting of nevirapine (NVP), zidovudine (ZDV) and lamivudine (3TC) presumptively based on the initial positive result.
This regimen will be continued to 42 weeks post menstrual age (PMA).
At this time, infants will be switched to LPV/r, ZDV and 3TC to be continued to 104 weeks or longer unless otherwise preferred by the treating clinician or if any clinical or laboratory contraindications are identified.
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Standard medication used to treat and prevent HIV/AIDS, specifically HIV-1. It is generally recommended for use with other antiretroviral medication. The initial dose of NVP will be 6 mg per kg per dose orally twice daily until 42 weeks gestational age (2 weeks of age for infants born at term) which is the dosing selected by the NIH International Maternal, Pediatric, Adolescent AIDS Clinical Trials (IMPAACT) Network.
Otros nombres:
An antiretroviral medication used to prevent and treat HIV/AIDS. It is generally recommended for use with other antiretroviral. ZDV will be dosed as per standard guideline and routine practices.
Otros nombres:
An antiretroviral medication used to prevent and treat HIV/AIDS. It is effective against both HIV-1 and HIV-2. 3TC will be dosed as per standard guideline and routine practices.
Otros nombres:
Lopinavir is an antiretroviral of the protease inhibitor class. It is used against HIV infections as a fixed-dose combination with another protease inhibitor, ritonavir. LPV/r will be dosed as per standard guideline and routine practices.
Otros nombres:
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Percent of patients with initial viral suppression
Periodo de tiempo: 24 weeks
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Suppression is defined as patients with plasma HIV RNA <50 copies/mL.
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24 weeks
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Percent of patients maintaining viral suppression
Periodo de tiempo: Between 24 and104 weeks
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Suppression is defined as patients with plasma HIV RNA <50 copies/mL.
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Between 24 and104 weeks
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Prevalence of CD4 percentage greater than 30
Periodo de tiempo: By 24 weeks and sustained through 104 weeks
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Patients that reached a normal CD4% level.
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By 24 weeks and sustained through 104 weeks
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Prevalence of growth along curve within one standard deviation or upward trend
Periodo de tiempo: Up to 104 weeks
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By comparing viral growth curves.
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Up to 104 weeks
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Prevalence of detection of specific HIV antibody classes
Periodo de tiempo: 24 and 104 weeks
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HIV antibody detection
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24 and 104 weeks
|
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Size of the viral reservoir (copies/million cell)
Periodo de tiempo: Up to 104 weeks
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Quantification of viral reservoir
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Up to 104 weeks
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Colaboradores e Investigadores
Publicaciones y enlaces útiles
Publicaciones Generales
- Kuhn L, Paximadis M, Da Costa Dias B, Shen Y, Mncube S, Strehlau R, Shiau S, Patel F, Burke M, Technau KG, Sherman G, Loubser S, Abrams EJ, Tiemessen CT. Predictors of Cell-Associated Human Immunodeficiency Virus (HIV)-1 DNA Over 1 Year in Very Early Treated Infants. Clin Infect Dis. 2022 Mar 23;74(6):1047-1054. doi: 10.1093/cid/ciab586.
- Kuhn L, Strehlau R, Shiau S, Patel F, Shen Y, Technau KG, Burke M, Sherman G, Coovadia A, Aldrovandi GM, Hazra R, Tsai WY, Tiemessen CT, Abrams EJ; LEOPARD Study Team. Early antiretroviral treatment of infants to attain HIV remission. EClinicalMedicine. 2020 Jan 7;18:100241. doi: 10.1016/j.eclinm.2019.100241. eCollection 2020 Jan.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Actual)
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimar)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Mecanismos moleculares de acción farmacológica
- Agentes antiinfecciosos
- Agentes Antivirales
- Inhibidores de la transcriptasa inversa
- Inhibidores de la síntesis de ácidos nucleicos
- Inhibidores de enzimas
- Agentes Anti-VIH
- Agentes antirretrovirales
- Antimetabolitos
- Inhibidores de la proteasa
- Inhibidores del citocromo P-450 CYP3A
- Inhibidores de enzimas del citocromo P-450
- Inductores de enzimas de citocromo P-450
- Inductores de citocromo P-450 CYP3A
- Inhibidores de la proteasa del VIH
- Inhibidores de la proteasa viral
- Nevirapina
- Ritonavir
- Lopinavir
- Lamivudina
- Zidovudina
Otros números de identificación del estudio
- AAAO5011
- U01HD080441 (Subvención/contrato del NIH de EE. UU.)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
Marco de tiempo para compartir IPD
Criterios de acceso compartido de IPD
Tipo de información de apoyo para compartir IPD
- PROTOCOLO DE ESTUDIO
- SAVIA
- CIF
- CÓDIGO_ANALÍTICO
- RSC
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
producto fabricado y exportado desde los EE. UU.
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