Diagnosis of HIV and Early Antiretroviral Therapy Initiation Among HIV-1 Infected Infants

Study Overview
=================
Brief Summary
-----------------
The purpose of the study is to test the effect of the Alere™ q HIV-1/2 Detect (diagnostic assay) on uptake of HIV testing among HIV-exposed infants and young children, and health outcomes for HIV-infected infants and young children using a novel POC EID Community Model in Zambia. The study will also assess the feasibility of field implementation of this novel diagnostic tool and its acceptability among HIV-infected mothers and frontline health workers.

Detailed Description
-----------------
The purpose of the study is to test the effect of the Alere™ q HIV-1/2 Detect (diagnostic assay) on uptake of HIV testing among HIV-exposed infants and young children, and health outcomes for HIV-infected infants and young children through a novel POC EID Community Model in Zambia. The study will also assess the feasibility of field implementation of this novel diagnostic tool and its acceptability among HIV-infected mothers and frontline health workers. The knowledge generated from this study will enable the Zambia Ministry of Health (MOH) to make informed policy decisions about the implementation and scale up of point of care (POC) diagnostic tools for early infant diagnosis and pediatric HIV treatment programs in Zambia and the region.

Official Title
-----------------
To Improve Rates of Antiretroviral Therapy Initiation for HIV-1 Infected Infants Through Point-of-Care Diagnosis

Conditions
-----------------
HIV Infections, Hiv

Intervention / Treatment
-----------------
* Diagnostic Test: Alere Q Testing


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria include IYCs: 0 days (at birth) - 17 months of age; Probable or known HIV exposure documented through maternal sero-positivity or reactive infant HIV antibody test; The IYC must be born to mothers who: attended ≥1 ANC visits without HIV testing; or delivered at home and did not return for post-natal care at a health facility, and thus the mother or their child were not tested for HIV; or were documented as HIV-infected but never initiated ART; or disengaged from HIV care after ART initiation/have not returned for ARV refills; or have not returned to the facility with their infant for initial EID testing or follow-up EID testing (after a negative test at birth or 6 weeks); or IYC not tested 6 weeks after cessation of breastfeeding. With a parent/guardian ≥18 years of age, and willing and able to provide written informed consent in a study language (English, Nyanja, or Bemba). Exclusion criteria include IYCs: With documented age-appropriate, guideline-adherent receipt of DBS-based EID HIV PCR testing; Already known to be HIV-infected / receiving ART.

Ages Eligible for Study
-----------------
Minimum Age: 1 Minute
Maximum Age: 17 Months

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pre-Intervention Group<br>The Investigators will visit each of the selected 3 clusters (i.e. 6 primary health clinics) to construct a retrospective cohort of high-risk HIV-infected women who entered the national PMTCT program and received the SOC between June 1, 2017 and May 31, 2018. Using existing data through the electronic health record information (SmartCare and LIMS), the investigators will gather individual-level retrospective data on high-risk Mother-Infant Pairs (MIPs) from PMTCT enrolment through the child's ART enrolment, initiation, and retention rate at 3 months. | |
| Post-Intervention Group<br>Study Research Assistants (RA) will review routine patient files and registers, augmented by existing electronic health record information, to identify a new cohort of high-risk Mother-Infant Pairs (MIPs) at each study site between the dates of June 1, 2019 and May 31, 2020. The outreach team will include, at a minimum, the study RA, a study peer, and an HIV counselor from the health facility, who will carry the Alere™ q HIV-1/2 Detect with them. When the outreach team contacts a high-risk MIP at community level, the team will approach the MIP for study screening, consent, and enrolment procedures. Study staff will ask the parent/guardian if the parent/guardian would like the IYC to be tested at their home, at a community health post, or other private space in the community. The IYC will be tested using both the Alere™ q HIV-1/2 Detect platform and a reflex DBS PCR test to evaluate performance of the POC platform in a mobile setting against the gold standard. | Diagnostic Test: Alere Q Testing<br>* Infants of intervention clinics will have heelprick-obtained blood tested by standard of care method (SOC) and Alere™ q HIV-1/2 Detect Test Point of Care testing onsite (i.e. community, household, or facility level). Point-of-care (POC) testing results will be available in 52 minutes. HIV-infected infants, based on the Alere Q test result, will start ART as soon as possible and start routine SOC visits at weeks 2, 4, 8, 12, 16, 20, 24, 36, and 48 post ART-initiation. Study data will be obtained on first 4 routine visits after ART initiation (3 months). Infants will return for results of DBS-based DNA PCR testing. Positive SOC infants remain on ART/study follow-up. Negative POC test/negative SOC infants will attend only routine care visits and continue on HIV prophylaxis per national guidelines. Discordant results require DNA PCR test, with positive results continuing ART, negative results being repeated for confirmation before discontinuation.<br>* Other names: Alere™ q HIV-1/2 Detect Test Point-of-Care Testing;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Uptake of Antiretroviral Therapy (ART) among HIV-infected Infants and Young Children (IYC) | Number of IYCs who were initiated on ARVs following a positive HIV test divided by the number of IYCs who tested positive for HIV. | Baseline to 18 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Age at first early infant HIV testing among HIV-exposed IYCs | Average chronological ages of all IYCs when presenting for initial EID HIV testing. | Baseline to 18 months | 
| 3-month survival for HIV-infected IYC receiving ART | Number of HIV-infected IYCs receiving ART who presented alive at 3 month visit divided by the total number of HIV-infected IYCs enrolled into ART. | Baseline to 18 months | 
| 3-month retention in care for HIV-infected IYC receiving ART | Number of HIV-infected IYCs receiving ART who were retained in care at 6 month visit divided by the total number of HIV-infected IYCs enrolled in ART. | Baseline to 18 months | 
| Time to ART initiation among HIV-infected IYCs using Alere™ q HIV-1/2 Detect | Average time of ART initiation by IYCs who present for at initial HIV test following positive screening test within 17 months of age. | Baseline to 18 months | 
| Describe knowledge of HIV-infected mothers regarding the Alere™ q HIV-1/2 Detect platform and POC EID Community Model | A pre-defined set of questions will be asked to all the parent/guardians to evaluate their knowledge regarding the Alere ™ q HIV-1/2 Detect platform and POC EID Community Model. The Investigators will enroll a total of 20 parents/guardians of HIV-exposed IYC (3-4 will be recruited from each clinic) to participate in in-depth interviews (IDIs). | Baseline to 18 months | 
| Describe attitudes of HIV-infected mothers regarding the Alere™ q HIV-1/2 Detect platform and POC EID Community Model | A pre-defined set of questions will be asked to all the parent/guardians to evaluate their attitudes regarding the Alere ™ q HIV-1/2 Detect platform and POC EID Community Model. The Investigators will enroll a total of 20 parents/guardians of HIV-exposed IYC (3-4 will be recruited from each clinic) to participate in IDIs. | Baseline to 18 months | 
| Describe preferences of HIV-infected mothers regarding the Alere™ q HIV-1/2 Detect platform and POC EID Community Model | A pre-defined set of questions will be asked to all the parent/guardians to evaluate their knowledge regarding the Alere ™ q HIV-1/2 Detect platform and POC EID Community Model. The Investigators will enroll a total of 20 parents/guardians of HIV-exposed IYC (3-4 will be recruited from each clinic) to participate in IDIs. | Baseline to 18 months | 
| Characterize feasibility of using the Alere™ q HIV-1/2 Detect platform and POC EID Community Model by the health care workers | A pre-defined set of questions will be asked to all the healthcare providers to characterize the feasibility of using the Alere ™ q HIV-1/2 Detect platform and POC EID Community Model. The Investigators will enroll a total of 20 healthcare providers who have used the platform to participate in IDIs. | Baseline to 18 months | 
| Characterize the acceptability of using the Alere™ q HIV-1/2 Detect platform and POC EID Community Model by the health care workers | A pre-defined set of questions will be asked to all the healthcare providers to characterize the acceptability of using the Alere ™ q HIV-1/2 Detect platform and POC EID Community Model. The Investigators will enroll a total of 20 healthcare providers who have used the platform to participate in IDIs. | Baseline to 18 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
HIV, EID HIV, Early Infant Diagnosis, Point of Care, Infant