Background
ACT (NCT05335590) is an ongoing observational study that aims to evaluate tenofovir-diphosphate (TFV-DP) concentrations in dried blood spots (DBS) among persons with HIV (PWH) receiving tenofovir alafenamide (TAF)-based antiretroviral therapy (ART) with suppressed compared with detectable HIV-1 RNA. Previously, QUANTI-TAF (NCT04065347) reported a pharmacokinetic (PK)-based TFV-DP in DBS benchmark of ≥1800 fmol/punches for PWH with ≥85% adherence using digital pills to objectively quantify adherence. We investigated the relationship between this concentration threshold and HIV-1 RNA suppression (<200 c/mL) in the ACT Study.
Methods
PWH prescribed TAF-based ART (25mg ± booster or 10mg + booster) for ≥3 months were prospectively enrolled and completed up to three convenience-based visits within 48 weeks during which HIV-1 RNA and DBS were collected. Results through July 18, 2024 were included in analysis. We reported TFV-DP in DBS mixed model estimates as geometric mean (GM [95% CI]) and used generalized linear mixed effects models with a logit link to estimate the odds ratio (OR [95% CI]) for HIV-1 RNA suppression (<200 c/mL) according to dichotomized TFV-DP in DBS (<1800 or ≥1800 fmol/punches).
Results
Paired TFV-DP in DBS and HIV-1 RNA results were available in 69 participants (205 person-visits): 61 (88%) males, 6 (9%) females, and 2 (3%) transgender persons; 63 (91%) were receiving unboosted TAF 25mg or boosted TAF 10mg. Median (IQR) age was 55 (42-61) years. HIV-1 RNA was <20, 20-199, and ≥200 c/mL at 141 (69%), 51 (25%), and 13 (6%) visits, respectively. GM (95% CI) TFV-DP in DBS for PWH with HIV-1 RNA <20, 20-199, and ≥200 c/mL was 3583 (3102, 4138), 3314 (2413, 4551), and 898 (565, 1428) fmol/punches, respectively (Figure). For TFV-DP in DBS ≥1800 fmol/punches, the OR for an individual to have HIV-1 RNA <200 c/mL was 39.2 (95% CI: 2.4, 471.2; P=0.003) compared with TFV-DP in DBS <1800 fmol/punches.
Conclusions
Our previously established PK-based TFV-DP in DBS benchmark of ≥1800 fmol/punches was associated with HIV-1 RNA suppression (<200 c/mL) among PWH receiving TAF-based ART, while TFV-DP in DBS was similar in those with HIV-1 RNA <20 and 20-199 c/mL. Given the small number of visits with HIV-1 RNA ≥200 c/mL, additional data will confirm the additional benchmark(s) to predict viral breakthrough.
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