Project Details

Using novel point-of-care HIV drug resistance testing to optimize viral suppression rates among children living with HIV (Opt4Kidsplus)

Rena Patel, MD, MPH

Summary

BACKGROUND: Children and adolescents living with HIV (CALWH) under 15 years of age receiving antiretroviral treatment (ART) and living in low and middle-income countries (LMIC) have suboptimal viral suppression (VS), the hallmark of successful HIV treatment. Currently, an estimated 1.7 million children ages 0-14 years and 1.7 million adolescents 10-19 years are living with HIV, with 150,000 children and 170,000 adolescents newly diagnosed with HIV annually, with the majority living in sub-Saharan Africa. CALWH are less likely to achieve VS and more likely to develop drug resistance (DR) than adults. Additionally, among children with virologic failure in Kenya, over 90% have drug resistance mutations (DRM), putting them at risk for clinical deterioration and limiting future drug options. GAP: DRM testing in Kenya, a heavily-burdened country for HIV, is currently very limited leaving clinicians without critical information that impacts the clinical management of children with HIV. Point-of-care drug resistance mutation testing may have the potential to significantly improve the management of children with HIV who are failing treatment by rapidly informing clinicians on what drugs will be effective. HYPOTHESIS: We hypothesized that a novel point-of-care DRM test, OLA Simple, will identify resistance mutations with sensitivity and specificity comparable to traditional resistance testing. Further, we hypothesized that OLA Simple’s usability will be rated highly, and its costs/sample tested will be lower than traditional consensus sequence testing. METHODS: We leveraged the NIH-funded Opt4Kids study-a randomized, controlled study to pilot the use of point-of-care viral load testing among 704 children aged 1-14 years on ART in Kisumu, Kenya implemented from March 2019 to December 2020- to validate the use of OLA Simple through retrospective batch testing of already collected blood samples tested via the “gold-standard” consensus sequencing (CS) method. We also explored usability and costs of OLA Simple use in Kenya. In order to evaluate usability of the OLA Simple assay, we administered a survey before and after the OLA Simple training. We designed the survey according to Nielsen’s usability framework, which entails domains of learnability, efficiency, memorability, error, and satisfaction. We used a microcosting technique to determine costs associated with OLA Simple use. RESULTS: Utilizing DRM data from the Opt4Kids study, we identified the seven most common and clinically significant DRM among CALWH with virologic failure on ART in Kenya. We then adapted the original OLA Simple assay, which was initially set-up to detect the nucleos(t)ide reverse transcriptase inhibitor (NRTI) mutations K65R and M184V and non-nucleos(t)ide reverse transcriptase inhibitor (NNRTI) mutations K103N, Y181C, and G190A, to include additional NRTI mutations, L74V and Y115F (which confer high-level resistance to abacavir), which were identified via CS results for participants undergoing DRM testing. This 7-codon assay was then produced for testing in Kenya. From March to June 2022, six total Kenyan laboratory technicians were successfully trained and tested a total of 87 study samples at two WHO-certified molecular laboratories in Kenya. The analysis comparing the performance of the OLA Simple assay against the CS results is currently under way. Our usability evaluation assessed a total of 13 laboratory technicians who took part in the OLA Simple training (who are separate from the six technicians who conducted the validation study for the OLA Simple noted above). The median age was 33 years with a median of 7 years of working in a laboratory setting. All of the lab staff were experienced in using a micropipette, while 54% had prior experience with molecular tests and 46% had set up and ran a PCR. The technicians rated the OLA Simple high in all five domains, with highest reporting in memorability and satisfaction domains. Future changes in the assay will be focused on improved efficiency. Micro-costing analyses for OLA Simple are underway. IMPACT: Findings from this study will help prepare the OLA Simple technology for clinical use, where rapid return of HIV drug resistance testing results, within the same clinical visit, could lead to change in clinical management. This study will also directly inform treatment monitoring algorithms in LMIC for CALWH and help achieve the UNAIDS 95-95-95 goals.

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