Background:
Multiple barriers limit participation of people with HIV (PWH) in studies in which frequent viral load (VL) monitoring is required such as cure studies involving a treatment interruption (ATI). Convenient, home-based VL testing may increase equitable participation. Here we report a novel VL test based on capillary blood collection, comparing its specificity and sensitivity to conventional clinic-based plasma-based VL (pVL).
Methods:
We enrolled 21 PWH (5% female, 67% African American, mean age of 51 years) undergoing planned ATIs as part of the BEAT-HIV trial (NCT03588715). At contiguous visits (mean 20.5), we collected A) capillary blood using two 4-well Tasso-M50 devices, and B) matched plasma samples. Between visits, participants self-collected capillary blood using two devices that were mailed back (home collection). We employed a robotic automation process for magnetic bead RNA extraction and RT-qPCR readout with dual LTR/GAG FAM-labeled primers that amplify on the same fluorescence channel. Samples and standards underwent qPCR in duplicate.
Results:
The devices were well-accepted, with a collection failure rate <10%. We analyzed a total of 5392 M50 PCR reads (3058 clinic, 2334 home collection). Among the 14 participants where M50 background levels could be determined from ≥ 4 weeks of suppressive treatment, M50 VL 2x above median background was predictive of matched pVL ≥ 200 c/mL (Figure 1. Sensitivity 66%, specificity 81%, PPV 71%, NPV 76%, ROC curve AUC 85%). When M50 VL was < median background, pVL was reliably low (NPV 84% for pVL ≥ 200 c/mL, NPV 90% for pVL ≥ 1000 c/mL). 13 of 14 (93%) participants experienced an increase in M50 VL at the collection immediately following pVL rebound ≥ 200 c/mL (median increase 9-fold, range 1.8- to >1000-fold); the remaining participant experienced an increased M50 VL at the subsequent collection (to 1.6-fold above background). An M50 VL ≥ 2x background was always followed by pVL rebound ≥ 200 c/mL within 4 weeks.
Conclusions:
Our new M50 assay showed good NPV for pVL > 200 c/ml in a cohort of PWH undergoing ATI. This suggests that, upon clinical validation, the assay could be used for home monitoring of VL during ATIs. This approach could enhance equitable participation in HIV research by minimizing participants’ visit burden. Other potential applications, such as monitoring new infections in prophylaxis studies or assessing changes in residual cell-associated HIV in cure studies, are warranted.
