Latency and Early Neonatal Provision of Antiretroviral Drugs Clinical Trial (LEOPARD)

Columbia University

Status and phase: Completed; Phase 4

Conditions: HIV

Treatments: Drug: Zidovudine; Drug: Lamivudine; Drug: Nevirapine; Drug: LPV/r

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT02431975

U01HD080441 (U.S. NIH Grant/Contract)

AAAO5011

Details and patient eligibility

About

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.

Full 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.

Enrollment: 73 patients

Sex: All

Ages: Under 48 hours old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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73 participants in 1 patient group

Early ART

Experimental group

Description:

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.

Treatment:

Drug: LPV/r

Drug: Nevirapine

Drug: Lamivudine

Drug: Zidovudine