HIV
Conditions
Keywords
HIV, infant, antiretroviral therapy, highly active, antiretroviral agents
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.
Interventions
DRUGNevirapine
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.
DRUGZidovudine
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.
DRUGLamivudine
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.
DRUGLPV/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.
Sponsors
National Institutes of Health (NIH)
University of Witwatersrand, South Africa
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Columbia University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 48 Hours
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of patients with initial viral suppression | 24 weeks | Suppression is defined as patients with plasma HIV RNA \<50 copies/mL. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Prevalence of growth along curve within one standard deviation or upward trend | Up to 104 weeks | By comparing viral growth curves. |
| Prevalence of detection of specific HIV antibody classes | 24 and 104 weeks | HIV antibody detection |
| Size of the viral reservoir (copies/million cell) | Up to 104 weeks | Quantification of viral reservoir |
| Percent of patients maintaining viral suppression | Between 24 and104 weeks | Suppression is defined as patients with plasma HIV RNA \<50 copies/mL. |
| Prevalence of CD4 percentage greater than 30 | By 24 weeks and sustained through 104 weeks | Patients that reached a normal CD4% level. |
Countries
South Africa
Outcome results
None listed