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.
|HIV||Drug: Nevirapine Drug: Zidovudine Drug: Lamivudine Drug: LPV/r||Phase 4|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Latency and Early Neonatal Provision of Antiretroviral Drugs Clinical Trial|
- Percent of patients with initial viral suppression [ Time Frame: 24 weeks ]Suppression is defined as patients with plasma HIV RNA <50 copies/mL.
- Percent of patients maintaining viral suppression [ Time Frame: Between 24 and104 weeks ]Suppression is defined as patients with plasma HIV RNA <50 copies/mL.
- Prevalence of CD4 percentage greater than 30 [ Time Frame: By 24 weeks and sustained through 104 weeks ]Patients that reached a normal CD4% level.
- Prevalence of growth along curve within one standard deviation or upward trend [ Time Frame: Up to 104 weeks ]By comparing viral growth curves.
- Prevalence of detection of specific HIV antibody classes [ Time Frame: 24 and 104 weeks ]HIV antibody detection
- Size of the viral reservoir (copies/million cell) [ Time Frame: Up to 104 weeks ]Quantification of viral reservoir
|Actual Study Start Date:||August 2015|
|Estimated Study Completion Date:||July 31, 2020|
|Estimated Primary Completion Date:||July 31, 2020 (Final data collection date for primary outcome measure)|
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.
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.
Other Names:Drug: Zidovudine
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.
Other Names:Drug: Lamivudine
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.
Other Names:Drug: LPV/r
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.
Other Name: Ritonavir-boosted lopinavir
Please refer to this study by its ClinicalTrials.gov identifier: NCT02431975
|Contact: Louise Kuhn, PhDemail@example.com|
|Rahima Moosa Mother and Child Hospital||Recruiting|
|Johannesburg, Gauteng, South Africa|
|Contact: Ashraf Coovadia, MBChB +27 114709290 Ashraf.Coovadia@wits.ac.za|
|Contact: Karl Technau, MBChB firstname.lastname@example.org|
|Principal Investigator:||Louise Kuhn, PhD||Columbia University|