Commercialization of PANDAA qDx for rapid drug resistance genotyping of protease inhibitor ART failures in resource-limited settings.

In 2020, 20M adults living with HIV in low- and middle-income countries (LMICs) are estimated to be receiving first-line antiretroviral therapy (ART) and this is expected to increase to 23.6M by 2024. This increase in access to first-line ART will have a cascade effect on the number of patients prescribed alternative, second-line protease- inhibitor (PI)-based ART following first-line ART failure. Studies of patients on PI-based ART have shown high rates of virologic failure at 12 and 24 months on ART, and patients maintained on failing PI-based regimens accumulate drug resistance mutations (DRMs) that hamper current and future treatment options. Despite calls for improved access to HIVDR diagnostics, the persistent urgent and unmet need for resistance genotyping has not been met, prohibiting the appropriate allocation of expensive third-line ART options. Early identification of second-line ART patients unable to achieve virologic suppression in the absence of HIV drug resistance (HIVDR) is crucial to prevent disease progression and curb HIV transmission. When virologic failure is adherence- mediate, third-line ART is unlikely to improve patient outcomes, while increasing healthcare system costs, and prematurely restricting future treatment options. Aldatu’s pioneering technology, PANDAA, uses adaptation to enable qPCR for DRM genotyping despite the high genomic variability of HIV. Our Phase II award preceding this CRP used PANDAA to successfully develop the first diagnostic for simultaneous focused genotyping of six resistance-conferring positions in the protease gene, and the K65R and M184VI DRMs. PANDAA accurately genotypes DRMs present ≥10% where conventional qPCR fails, with excellent sensitivity: as few as 100 DRM copies detected reproducibly even with allelic variants with known mismatches in the probe-binding sites. In this CRP, we build upon our recent product commercialization experience in the USA to create a diagnostic product for marketing and sale in LMICs. In the first year we will expand our existing quality management system (QMS) to be compliant with international standard for medical device manufacturing. This will align our manufacturing processes to achieve CE marking as an in vitro diagnostic (IVD). Concurrent with the establishment of our QMS we will expand our in-house manufacturing practices such that by the end of the second year we will have the capacity for the GMP production of ≥800, CE IVD HIVDR genotyping tests per a week in an ISO 134585-certified facility. This will be coordinated with implementing our go-to-market strategy to introduce the product in 3-5 short list countries, and we will have identified and vetted clinical study partners, distributors, and other regional partners to support Aldatu in negotiations and contracting with local partners and facilitating engagement with Ministries of Health. Our go-to-market launch will be preceded by early site evaluations by collaborators in key target markets where they will perform side-by-side comparisons with Sanger sequencing and evaluate our software. The net result will be the manufacturing and regulatory qualification of an HIVDR genotyping diagnostic that significantly reduces test complexity, time burden and costs, without sacrificing accuracy.