Latency and Early Neonatal Provision of Antiretroviral Drugs Clinical Trial

HIV Clinical Trial

— LEOPARD  

Official title:

Latency and Early Neonatal Provision of Antiretroviral Drugs Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02431975
• Other study ID #: AAAO5011
• Secondary ID: U01HD080441
• Status: Completed
• Phase: Phase 4
• Start date: August 2015
• Est. completion date: April 30, 2020

Study information

• Verified date: July 2020
• Source: Columbia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

Prevention of mother-to-child transmission (PMTCT) programs using antiretrovirals (ARVs) have had tremendous success in sub-Saharan Africa. However, HIV transmission continues to occur because (1) implementation of PMTCT is incomplete and (2) ARV interventions are not 100% effective in blocking infection. Thus the challenge of providing treatment to HIV-infected children is far from over. The capacity of early ART treatment to favorably influence the viral reservoir and potentially lead to post-treatment cessation viral control needs to be described in the population of infants, and to identify useful public health strategies.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 73
• Est. completion date: April 30, 2020
• Est. primary completion date: April 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 48 Hours

Eligibility

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.

Related Conditions & MeSH terms

• HIV

Intervention

Drug:
• Nevirapine
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.
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
South Africa	Rahima Moosa Mother and Child Hospital	Johannesburg	Gauteng

Sponsors (4)

Lead Sponsor	Collaborator
Columbia University	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), National Institutes of Health (NIH), University of Witwatersrand, South Africa

Country where clinical trial is conducted

South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent of patients with initial viral suppression	Suppression is defined as patients with plasma HIV RNA <50 copies/mL.	24 weeks
Secondary	Percent of patients maintaining viral suppression	Suppression is defined as patients with plasma HIV RNA <50 copies/mL.	Between 24 and104 weeks
Secondary	Prevalence of CD4 percentage greater than 30	Patients that reached a normal CD4% level.	By 24 weeks and sustained through 104 weeks
Secondary	Prevalence of growth along curve within one standard deviation or upward trend	By comparing viral growth curves.	Up to 104 weeks
Secondary	Prevalence of detection of specific HIV antibody classes	HIV antibody detection	24 and 104 weeks
Secondary	Size of the viral reservoir (copies/million cell)	Quantification of viral reservoir	Up to 104 weeks