Point-of-Care Virologic Testing to Improve Outcomes of HIV-Infected Children in Zambia: A Clinical Trial Protocol

Abstract

Introduction:In the absence of early infant diagnosis (EID) and immediate antiretroviral therapy (ART), some 50% of untreated HIV-infected infants die before age 2. Conventional EID requires sophisticated instruments that are typically placed in centralized or reference laboratories. In low-resource settings, centralized systems often lead to result turnaround times of several months, long delays in diagnosis, and adverse outcomes for HIV-infected children. Our clinical trial tests the effectiveness of a new point-of-care (POC) diagnostic technology to identify HIV-infected infants and start providing them life-saving ART as soon as possible.Methods and Design:The study uses a randomized, controlled design to test whether the Alere q platform for HIV DNA polymerase chain reaction (PCR) testing improves outcomes of HIV-infected children in Zambia. We aim to enroll 2867 HIV-exposed infants aged 4–12 weeks and to follow those who are HIV infected for 12 months as they receive HIV care at 6 public health facilities in Lusaka. The trial's primary endpoint is the proportion of HIV-infected infants in each study arm who start ART and remain alive, in care, and virally suppressed 12 months after their diagnostic blood draw.Discussion:Our trial will provide evidence for the incremental benefit of implementing a POC EID strategy in low-resource settings where only off-site PCR services are currently available. The results will be useful in guiding future decisions regarding investments in POC virologic testing as part of overall pediatric AIDS mitigation strategies in sub-Saharan Africa.Trial Registration:clinicaltrials.gov NCT02682810.

Significant Patient Impact Observed Upon Implementation of Point-of-Care Early Infant Diagnosis Technologies in an Observational Study in Malawi

“…To accurately diagnose HIV infection in infants, virological detection of HIV nucleic acid–based assays are required, as opposed to the common antibody-based HIV tests used to test older children and adults [ 8 ]. Nucleic acid testing in the laboratory requires sophisticated infrastructure, equipment, and skilled technicians that are often only available in central facilities [ 12 , 13 ]. This system presents a major bottleneck for timely EID, as sample transport from decentralized and rural clinics to central laboratories results in long test turnaround times of up to several months and families may not always return to receive test results [ 13 ].…”

New virological tools for screening, diagnosis and monitoring of hepatitis B and C in resource-limited settings

“…13 Non-immunological (nucleic acid testing) point-of-care tests New POC tests have emerged as a result of technological innovations, allowing for NAT testing in the absence of a sophisticated laboratory environment. [48][49][50] However, no POC test for HBV DNA is available yet, but several companies are working on such developments. In contrast, POC tests have been developed for HCV RNA.…”

“…Another platform, Alere TM q (Abbott, Chicago, IL), a battery-powered, fully automated, cartridge-based assay that does not require sample extraction is CE-marked for rapid HIV-1/2 RNA detection from capillary or venous whole blood in less than one hour. [48][49][50] An HCV RNA assay using small amounts of whole blood is in development with this and several other technologies. 55 Future developments will use smartphone applications, biosensors, lab-on-a chip NAT-based amplification and detection techniques and wearable devices, all of which will offer closer connection to the patient while substantially improving access to care.…”