CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

Results: N=84 participants (median age 54 [43, 59] years) receiving TAF for median 32 (18, 45) months were enrolled. Most were males (89%) receiving integrase strand transfer inhibitors (88%). Race/ethnicity was 55% White, 24% Black, and 21% Hispanic/Latino. TFV-DP Css in DBS (n=77) were median 3301 (2580, 4362) fmol/punches. PWH with ≤85% DOT adherence (n=8) had median 2998 (2152, 3610) fmol/punches; PWH with >85% DOT adherence (n=69) had median 3339 (2629, 4378) fmol/punches (A). TFV-DP Css in DBS were higher with boosted (b/) than unboosted (un/) ART. PWH receiving un/ART (n=72) had median 3274 (2542, 4232) fmol/punches; PWH receiving b/ART (n=5) had median 8210 (5893, 8760) fmol/punches (B). No HIV VL was >200 cps/mL. Low-level viremia (LLV) occurred at 60/335 (18%) visits from 33/84 (39%) participants (VL range: 20-149 cps/mL), with similar TFV-DP concentrations in DBS: median 3176 (2494, 4145) fmol/punches at LLV visits, median 3278 (2585, 4404) fmol/punches at suppressed (VL <20 cps/mL) visits. Digital pills were well tolerated. Conclusion: We describe initial TFV-DP benchmarks in DBS in PWH receiving TAF-based ART as digital pills to capture DOT adherence in a real-world clinical study. We observed higher TFV-DP Css with b/ART than un/ART. The lack of relationship between LLV and TFV-DP concentrations in DBS in this cohort suggests mechanisms other than variable adherence for LLV. Future analyses will explore additional factors that may be associated with LLV.

we present a map of ARVs penetration across different post-mortem tissue homogenates from altruistic participants recruited in the Last Gift program. Methods: People with HIV with terminal illness who gave written informed consent were enrolled. All participants were on suppressive ART until the time of death. Tissue samples were collected through rapid research autopsy (<6h after death) and immediately snap frozen in liquid nitrogen. Non-nucleosidic ARVs intra-tissue concentrations were determined through an UHPLC-MS/ MS validated method, with accuracy and precision within the requirements of FDA guidelines, after homogenization of 2 aliquots (about 30 mg) of tissue for each sample. The results were normalized by weight and the mean values were reported as results. Results: 21 tissue biopsies per participant were isolated from different anatomical sites in 6 volunteers on different ART regimens: 3 on tenofovir alafenamide/emtricitabine (TAF/FTC) and dolutegravir (DTG), 1 on TAF/ FTC+DTG plus rilpivirine (RPV), 1 on DTG and darunavir/cobicistat (DRV/c) and 1 on abacavir/lamivudine (ABC/3TC)/DTG. DTG had a higher exposure in intestine, kidney, and liver and lower in central nervous system (CNS) and pancreas (p<0.001 and p=0.012 compared to intestine, respectively). DRV, RPV and cobicistat (COBI), in a lower sample size (1 participant/drug), showed a higher exposure in liver and intestine, compared with other anatomical sites as reported in Fig.1. No statistical differences were observed in the overall ARVs penetration in different areas in the brain (p=0.971) and intestine tracts (p=0.941). Conclusion: Scarce data on human intra-tissue ARV penetration are reported in literature. This is the first study to report different ARV concentrations in different anatomical sites in humans. Previous studies on non-human primates showed similar results about the poor, but rather uniform, concentrations of DTG in all the districts of the CNS, and higher concentrations in kidney and intestine.

Poster Abstracts

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Factors Affecting TFV-DP Concentrations in PBMC and Relationships With DBS in PWH on TAF-Based ART Stefanie Schwab 1 , Mary Morrow 1 , Corwin Coppinger 1 , Ryan P. Coyle 1 , Vincent Mainella 1 , Sarah C. Mann 1 , Nicholas Barker 1 , Lucas Ellison 1 , Samuel L. Ellis 1 , Pamela E. Alpert 2 , Lane Bushman 1 , Samantha MaWhinney 1 , Kristina M. Brooks 1 , Jose R. Castillo-Mancilla 1 , Peter L. Anderson 1 1 University of Colorado Anschutz Medical Campus, Aurora, CO, USA, 2 etectRx, Gainesville, FL, USA Background: Relationships between tenofovir-diphosphate (TFV-DP) steady state concentrations (Css) in peripheral blood mononuclear cells (PBMCs), dried blood spots (DBS), and adherence have not been well-described in people with HIV (PWH) on tenofovir-alafenamide (TAF)-containing antiretroviral therapy (ART). Our objectives were to assess the influence of adherence and other factors on TFV-DP Css in PBMCs, and to examine relationships between TFV-DP Css in DBS and PBMC. Methods: QUANTI-TAF was a 16-week observational study that enrolled PWH on TAF-based ART for >6 months. Study visits occurred at weeks 0, 4, 8, 12, and 16. Blood was collected for TFV-DP in DBS (2x7mm punches) and PBMC (per 106 cells) at each visit and quantified using validated LC-MS/MS methods. Adherence was quantified using TAF-based ART co-encapsulated with an ingestible biosensor (calculated as # ingestions in the 10 days before each visit). Week 4 TFV-DP Css in PBMC were dichotomized by 5-8 vs. 9-10 days of dosing in the 10-day window. A linear mixed-effects model with backward selection was used to evaluate factors associated with TFV-DP Css in PBMC (all visits), and included adherence, age, sex, weight, BMI, race, eGFR, CD4, and NNRTI or INSTI. Pearson correlation compared week 4 TFV-DP Css in DBS and PBMC. Results: Data were available in 84 PWH (55% White, 24% Black, 21% Hispanic/ Latino) on TAF for median (IQR) 32 (18, 45) months (79 unboosted [un/], 5 boosted [b/]). Median (IQR) age was 54 (43, 59) years; most were males (89%) on INSTIs (88%). Median TFV-DP Css in PBMC in PWH on un/ART were 32% higher for 9-10 vs. 5-8 days of dosing (Fig. A). Median TFV-DP Css for b/ART was 72% higher than un/ART (1007 [IQR: 868, 1297] vs. 585 [IQR: 459, 780] fmol/106 cells, respectively). Ten-day adherence was the only significant predictor, with every 10% adherence increase associated with an average TFV-DP in PBMC increase of 32 (95% CI: 14, 49; P=0.0005) fmol/106 cells. Week 4 TFV-DP Css in DBS and PBMC were moderately correlated (Fig. B).

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Tenofovir Diphosphate Benchmarks in Dried Blood Spots in PWH Receiving TAF-Based ART (QUANTI-TAF) Ryan P Coyle 1 , Mary Morrow 1 , Vincent Mainella 1 , Sarah C. Mann 1 , Nicholas Barker 1 , Lucas Ellison 1 , Samuel L. Ellis 1 , Pamela E. Alpert 2 , Tony C. Carnes 2 , D. Eric Buffkin 2 , Lane Bushman 1 , Samantha MaWhinney 1 , Kristina M. Brooks 1 , Jose R. Castillo-Mancilla 1 , Peter L. Anderson 1 1 University of Colorado Anschutz Medical Campus, Aurora, CO, USA, 2 etectRx, Gainesville, FL, USA Background: Tenofovir diphosphate (TFV-DP) concentrations in dried blood spots (DBS) in people with HIV (PWH) receiving tenofovir alafenamide (TAF)- based antiretroviral therapy (ART) are not defined. QUANTI-TAF (NCT04065347) aimed to establish adherence:concentration benchmarks in PWH receiving TAF based ART by quantifying TFV-DP concentrations in DBS, leveraging digital pills to organically capture directly observed therapy (DOT) adherence in a real-world clinical cohort. Methods: PWH receiving TAF-based ART for ≥6 months were prospectively enrolled in a 16-week pharmacokinetic study. Digital pills captured DOT adherence by co-encapsulation of each TAF-based ART dose with an ingestible biosensor powered by gastric fluid. Blood for TFV-DP concentrations in DBS (fmol/2x7mm punches) was collected at each visit and quantified using a validated LC-MS/MS method. TFV-DP steady-state concentrations (Css) in DBS were assessed at weeks ≥12 overall, by DOT adherence, booster status, and HIV viral load (VL; all weeks), reported as median (IQR).

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