Point-of-Care HIV Testing and Early Dolutegravir Use for Infants

Study Overview
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Brief Summary
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This study is being conducted to explore the feasibility of implementing targeted birth HIV testing of high-risk neonates using facility-based point-of-care (POC) HIV diagnostics, and to improve the ability to implement the best standard-of-care treatment possible. Infants found to be HIV infected will be immediately offered enrollment into a dolutegravir (DTG) antiretroviral treatment study cohort (if maternal consent is granted) or referred for treatment at a government facility. Infants who enter the study treatment cohort will be prospectively followed through 96 weeks of age. ART will follow Botswana guidelines.

Official Title
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Point-of-Care HIV Testing and Early Dolutegravir Use for Infants

Conditions
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HIV

Intervention / Treatment
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* Diagnostic Test: Point-of-Care Cepheid Xpert HIV-1
* Drug: DTG/ABC/3TC


Participation Criteria
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Eligibility Criteria
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Inclusion criteria for point-of-care infant HIV testing: Mother 18 years of age or older Mother willing and able to provide verbal consent for infant testing Infant birth weight ≥1.5kg Presence of any of the following risk factors: <12 weeks of ART prior to delivery (including no ART); Known HIV-1 viremia (above level of detection) for last test performed or at any time >24 weeks gestation in pregnancy; CD4 cell count known to be <350 cells/mm3 within the past year; Self-described poor adherence in pregnancy (1 or more complete days of missed ART) Exclusion criteria for point-of-care infant HIV testing: 1) Medical condition making it unlikely that the infant will survive to 24 months Inclusion criteria for infant longitudinal treatment cohort: Mother 18 years of age or older Mother willing and able to provide written informed consent for study participation for herself and her infant Positive point-of-care HIV screening for infant (HIV DNA PCR pending or completed) Infant eligible for ART treatment in accordance with the Botswana government program Infant birth weight ≥1.5 kg Exclusion criteria for infant longitudinal treatment cohort: Medical condition making it unlikely that the infant will survive to 24 months Infant unable to start treatment-dose ART < 168 hours of age Infant unable to attend follow-up visits at a BHP study clinic in Gaborone or Francistown
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: HIV-exposed neonates<br>Point-of-care HIV testing at birth | Diagnostic Test: Point-of-Care Cepheid Xpert HIV-1<br>* Post-partum HIV-positive women with pre-determined risk factors for vertical HIV transmission will be offered point-of-care HIV testing for their newborns for early infant HIV diagnosis.<br>|
| Other: HIV-positive infants identified through birth HIV screening<br>Early antiretroviral treatment per standard of care, including dolutegravir-based regimen beginning at 4 weeks of age for infants weighing at least 3.0kg. | Drug: DTG/ABC/3TC<br>* Infants will be started on a combination of NVP/ZDV/3TC. A switch to DTG/ABC/3TC will occur for all infants at or after 4 weeks (28 days) post-delivery for those weighing ≥3kg. Dosing of all ART will be weight-based by the Botswana treatment guidelines.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of high-risk HIV-exposed infants identified and tested | Analysis will largely be descriptive, highlighting the proportion of high-risk infants identified and tested at each facility. Proportions will be determined by populating actual numbers approached and screened matched against exact denominators obtained from surveillance data. | within 72 hours of life | 
| Median time to HIV diagnosis and treatment-dose ART | We will describe the proportion of high-risk infants found to be HIV positive per risk category and compare this to findings from another cohort study of early-treated children. Average time to HIV diagnosis and treatment initiation will also be described. | 7 days | 
| The proportion of children with HIV-1 RNA <40 copies/mL at 12 weeks on ART | We will compare time to viral suppression and the proportion with complete HIV-1 RNA suppression (<40 copies/mL) at 12 weeks from ART start between infants on early DTG with another cohort of children on early LPV/r. | 12 weeks on ART | 
| The proportion of children with successful DTG-based treatment through 96 weeks on ART | We will compare the proportion with complete HIV-1 RNA suppression and no need for treatment modification at all visits through 96 weeks between infants on early DTG with another cohort of children on early LPV/r. | 96 weeks on ART | 
| The proportion of infants with grade 3 or 4 adverse events/hospitalization/death | We will compare the proportion with grade 3 or 4 adverse events through 96 weeks between infants on early DTG with another cohort of children on early LPV/r. | 96 weeks on ART |