Adherence insights from TAF/FTC-based art co-encapsulated with an ingestible sensor among virologically suppressed persons with HIV

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Adherence insights from TAF/FTC-based art co-encapsulated with an ingestible sensor among virologically suppressed persons with HIV

Ryan Coyle¹, Vincent Mainella¹, Mary Morrow¹, Sarah Mann¹, Stefanie Schwab¹, Corwin Coppinger¹, Nicholas Barker¹, Samuel Ellis¹, Tony Carnes², Pamela Alpert², Lucas Ellison¹, Lane Bushman¹, Kristina Brooks¹, Samantha MaWhinney¹, Jose Castillo-Mancilla¹ and Peter Anderson¹

¹University of Colorado Anschutz Medical Campus; ²etectRx

Background: QUANTI-TAF (NCT04065347) measured adherence for approximately 16 weeks using digital pills with ingestible sensors (ID-Cap System, etectRx) paired with tenofovir diphosphate/emtricitabine triphosphate (TFV-DP/FTC-TP) concentrations in dried blood spots (DBS) among 84 persons with HIV (PWH) receiving daily oral tenofovir alafenamide/emtricitabine (TAF/FTC)-based antiretroviral therapy (ART) for ≥6 months. This analysis focused on digital pill adherence patterns.

Material and methods: We categorized each recorded dose by interval length (>36 h [late/missed]; 36–18 h [on-time]; <18 h [early/stacked]). Chi-squared tests compared the proportion of observed dosing intervals and detected vs. manually entered doses. Kaplan–Meier analysis evaluated digital pill system use from enrolment to end of study, censored at week 16. We used generalized estimating equations with a logit link to calculate the odds ratio (OR [95% CI]) of a missed dose according to day of the week, or between Sunday–Thursday and Friday–Saturday. We summarized HIV-1 RNA, adherence and TFV-DP/FTC-TP in DBS at visits with suppressed HIV-1 RNA (<200 copies/mL) and low (<85%) cumulative (enrolment to visit) digital pill adherence as proportion (%) or median (IQR).

Results: Overall, adherence was 93% (8650 recorded doses/9280 expected). Dosing intervals were mostly on-time (7991 [92%]), with smaller numbers of late/missed doses (356 [4%]) or early/stacked doses (303 [4%]), p < .0001. Significantly more doses were detected (7948 [92%]) than manually entered (702 [8%]), p < .0001. The proportion of participants on-study was 84/84 (100%) at week 4, 81/84 (96%) at week 8, 77/84 (92%) at week 12 and 73/84 (87%) at week 16. Median (IQR) cumulative adherence was 100% (100%–100%) at week 4 and 99% (96%–100%) at week 12 and at week 16. The OR (95% CI) for a missed dose was higher on Friday compared with Monday (1.35 [1.02, 1.79]; p = .04) or Tuesday (1.34 [1.04, 1.73]; p = .03), and on Saturday compared with Sunday (1.39 [1.08, 1.79]; p = .01), Monday (1.58 [1.14, 2.19]; p = .006), Tuesday (1.57 [1.23, 2.02]; p = .0004), Wednesday (1.38 [1.01, 1.88]; p = .04), or Thursday (1.47 [1.11, 1.96]; p = .008). Accordingly, the OR (95% CI) for a missed dose was higher on Friday–Saturday compared with Sunday–Thursday (1.37 [1.15, 1.63]; p = .0005). 335/404 total visits (83%) assessed HIV-1 RNA (all <200 copies/mL) and 247/335 (74%) of these visits also had cumulative adherence results (not measured before enrolment). 19/247 (8%) of these visits showed virologic suppression with low cumulative adherence: HIV-1 RNA was 0, <20 or between 26 and 86 copies/mL at 9/19 (47%), 4/19 (21%) and 6/19 (32%) visits, respectively. Median (IQR) cumulative adherence, TFV-DP in DBS and FTC-TP in DBS at these 19 visits was 79% (70%–82%), 2418 (2039–3444) fmol/punches and 2.79 (2.20–3.94) pmol/punches, respectively.

Conclusions: Digital pill system use remained high for 16 weeks and provided detailed adherence insights among virologically suppressed PWH receiving TAF/FTC-based ART. PWH receiving daily oral ART may stack doses to compensate for late/missed doses; missed doses were more likely to be on Friday–Saturday compared with Sunday–Thursday. Modern ART's potency is highlighted by virologic suppression even with intermittent non-adherence. Future research could leverage digital pill systems for adherence monitoring in clinical trials of novel oral dosing regimens such as long-acting weekly oral ART.