Clinical trial NCT02431975: Latency and Early Neonatal Provision of Antiretroviral Drugs Clinical Trial
Official title: Latency and Early Neonatal Provision of Antiretroviral Drugs Clinical Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV
Keywords: HIV
infant
antiretroviral therapy, highly active
antiretroviral agents
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: University of Witwatersrand, South Africa
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2015-05-01
Enrollment: 73
Sex: ALL
Maximum age (years): 48
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percent of patients with initial viral suppression
timeFrame: 24 weeks
Secondary outcomes:
measure: Percent of patients maintaining viral suppression
timeFrame: Between 24 and104 weeks
measure: Prevalence of CD4 percentage greater than 30
timeFrame: By 24 weeks and sustained through 104 weeks
measure: Prevalence of growth along curve within one standard deviation or upward trend
timeFrame: Up to 104 weeks
measure: Prevalence of detection of specific HIV antibody classes
timeFrame: 24 and 104 weeks
measure: Size of the viral reservoir (copies/million cell)
timeFrame: Up to 104 weeks
Other outcomes:
Locations:
city: Johannesburg
country: South Africa
facility: Rahima Moosa Mother and Child Hospital
state: Gauteng
Study officials:
affiliation: Columbia University
name: Louise Kuhn, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.