Presumptive and Definitive Virologic HIV Diagnosis in Hospitalized Malawian Infants
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Enrollment
- 300
- Locations
- 1
- Primary Endpoint
- ART initiation of HIV-infected infants
Study Overview
Brief Summary
Purpose: The purpose of this research study is to learn about two HIV tests - a clinical "presumptive diagnosis" (PD) that a trained healthcare provider can quickly use to determine if a child is likely to be HIV-infected and in need of HIV medicines and an "expedited" gold standard RNA-PCR test (expedited PCR) that is done at the UNC Project lab located at the hospital and the result given within 48 hours. Both of these tests can obtain results quickly while the current test called dried blood spot DNA-PCR goes to a lab and the result may take up to one month. The performance of PD and expedited PCR will be compared to one another with respect to HIV-infected infants correctly initiating life-saving antiretroviral therapy.
Participants: Hospitalized children younger than 12 months of age who are HIV DNA-PCR eligible at Kamuzu Central Hospital (KCH), in Lilongwe, Malawi. Other participants will be patient caregivers and clinical officers who provide healthcare for children that could be HIV-infected. Clinical officers will be trained to conduct the presumptive diagnosis test.
Procedures (methods): Patients will be randomized to either standard of care (PD and dried blood spot DNA-PCR) or expedited PCR. A consultant pediatrician and a clinical officer will perform the PD. If the PD or expedited PCR test results are positive, hospital care could include HIV medicine.
Detailed Description
Background A majority of HIV-infected children die by two years of age without antiretroviral therapy (ART). Unfortunately, diagnosing HIV in this age group is complex as it requires virologic testing. This has served as a barrier to younger HIV-infected (HIV+) children accessing ART in resource-constrained generalized epidemic countries. Malawi, a high HIV-prevalence country in sub-Saharan Africa, implemented a national early infant diagnosis (EID) program utilizing virologic testing with dried blood spots (DBS) DNA PCR technology in 2007 to address this gap.
In coordination with the national EID program in 2008, we implemented a routine HIV testing strategy within the pediatric inpatient ward at Kamuzu Central Hospital (KCH) that incorporated DBS. While our initial program results have been encouraging, we have observed that only 50.2% of DBS recipients have returned for their test results after hospital discharge, draining resources and reducing the potential impact of definitive virologic testing and early diagnosis. DBS technology is a contributing factor to low patient follow-up as it requires burdensome transport and lengthy processing by highly trained laboratory personnel, requiring patients to return several weeks after testing for their results. Currently in Malawi, as is the case throughout sub-Saharan Africa, definitive virologic testing that provides test results prior to hospital discharge is not routinely available.
Two alternatives that could potentially strengthen EID and pediatric ART access are the routine use of presumptive diagnosis (PD), or a clinical HIV diagnostic algorithm in young children, as an adjunct to DBS and definitive inpatient virologic testing that provides results before hospital discharge ("expedited PCR") instead of PD and DBS. This research proposal primarily aims to validate PD testing as well as assess the impact of PD and expedited PCR upon patient outcomes within the established inpatient pediatric HIV testing system at KCH.
RESEARCH QUESTION TO BE ADDRESSED BY THIS PROPOSAL Is presumptive diagnosis, as an adjunct to dried blood spot DNA PCR, a valid approach for diagnosing HIV in hospitalized Malawian children younger than 12 months of age, and how does this strategy, compared to an expedited inpatient virologic diagnosis, affect patient outcomes?
RATIONALE FOR RESEARCH
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Diagnostic
- Masking
- None
Eligibility Criteria
- Ages
- — to 12 Months (Child)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Male and female children
- •Less than 12 months of age
- •Inpatient at KCH
- •HIV DNA-PCR test eligible
- •No prior definitive PCR test result
Exclusion Criteria
- •Caregiver does not want to be contacted by study team
- •Mother initiated on ART prior to pregnancy
Arms & Interventions
Point of Care HIV RNA PCR
Patients randomized to this arm will be followed prospectively from the time of clinical evaluation in the hospital until 12 months after returning for outpatient care at the KCH HIV clinic. The counselor will collect infant blood for point of care RNA PCR testing, number the sample, and transport it to the central laboratory for processing. Patients determined to be HIV-uninfected or HIV-exposed uninfected will not continue in the study beyond virologic test result disclosure, which will occur as an inpatient at KCH for this arm. If the patient does not return for outpatient care for three months after hospitalization then the patient's participation in the study will end.
Intervention: Point of care HIV RNA PCR (Device)
Standard of Care
Patients randomized to this arm will be followed prospectively from the time of clinical evaluation in the hospital until 12 months after returning for outpatient care at the KCH HIV clinic. The counselor will collect infant blood for dried blood spot DNA PCR testing, number the sample, and transport it to the central laboratory for processing. If the patient is PD positive then the patient will be offered ART initiation prior to hospital discharge.
Patients determined to be HIV-uninfected or HIV-exposed uninfected will not continue in the study beyond virologic test result disclosure, which will occur as an outpatient at KCH for this arm. If the patient does not return for outpatient care for three months after hospitalization then the patient's participation in the study will end.
Outcomes
Primary Outcomes
ART initiation of HIV-infected infants
Time Frame: Participants will be followed for an expected average of 2 months, or until their HIV-status is confirmed
The primary outcome will be the proportion of HIV+ children initiated on ART in the hospital. We will need a sample size of 400 infants assuming the standard of care will initiate 60% and the experimental group will initiate 85% of HIV-infected infants on ART prior to hospital discharge, respectively. These assumptions also take into consideration a predicted inpatient HIV-prevalence in HIV-exposed infants of 25% and a 5% absconding rate, using a confidence interval of 10% and confidence level of p \< 0.05.
Secondary Outcomes
No secondary outcomes reported