scholarly journals Low-level viremia is associated with cumulative adherence to antiretroviral therapy in persons with HIV

2021 ◽  
Author(s):  
Jose R Castillo-Mancilla ◽  
Mary Morrow ◽  
Ryan P Coyle ◽  
Stacey S Coleman ◽  
Jia-Hua Zheng ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Dried Blood Spots ◽  
Odds Ratios ◽  
Antiretroviral Adherence ◽  
Low Level ◽  
Blood Spots ◽  
Tenofovir Diphosphate

Abstract The drivers of low-level viremia (LLV) between 20-200 copies/mL remain unclear. In 1,042 person-visits from 497 persons with HIV on TDF-containing ART, the association between LLV and cumulative antiretroviral adherence (quantified using tenofovir diphosphate (TFV-DP) in dried blood spots) was assessed. Lower TFV-DP levels were associated with higher odds of LLV. As TFV-DP (fmol/punch) categories decreased from >1,650 to 800-1,650; 800-1,650 to <800; and >1,650 to <800, the adjusted odds ratios for LLV versus HIV VL <20 copies/mL were: 2.0 [1.2, 3.1]; 2.4 [1.1, 5.0]; and 4.6 [2.2, 9.9], respectively. This suggests that adherence could impact LLV.

scholarly journals Associations Between Tenofovir Diphosphate in Dried Blood Spots, Impaired Physical Function, and Fracture Risk

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Mona Abdo ◽  
Ryan P Coyle ◽  
Sharon M Seifert ◽  
Jose R Castillo-Mancilla ◽  
Catherine M Jankowski ◽  
...  
Keyword(s):  
Fracture Risk ◽  
Physical Function ◽  
Lean Body Mass ◽  
Body Mass ◽  
Fat Mass ◽  
Dried Blood Spots ◽  
Blood Spots ◽  
Hip Bmd ◽  
Total Fat ◽  
Tenofovir Diphosphate

Abstract Background In this study, we evaluate associations between cumulative antiretroviral adherence/exposure, quantified using tenofovir diphosphate (TFV-DP) in dried blood spots (DBS), and human immunodeficiency virus (HIV)-related aging factors. Methods This is a cross-sectional analysis of younger (ages 18–35) and older (ages ≥60) persons with HIV (PWH) taking TFV disoproxil fumarate. Tenofovir diphosphate concentrations were quantified in DBS. Linear and logistic regression models were used to evaluate associations between TFV-DP and bone mineral density (BMD), physical function, frailty, and falls. Results Forty-five PWH were enrolled (23 younger, 22 older). Every 500 fmol/punch (equivalent to an increase in ~2 doses/week) increase in TFV-DP was associated with decreased hip BMD (−0.021 g/cm2; 95% confidence interval [CI], −0.040 to −0.002; P = .03). Adjusting for total fat mass, every 500 fmol/punch increase in TFV-DP was associated with higher odds of Short Physical Performance Battery impairment (score ≤10; adjusted odds ratio [OR], 1.6; 95% CI, 1.0–2.5; P = .04). Every 500 fmol/punch increase in TFV-DP was associated with slower 400-meter walk time (14.8 seconds; 95% CI, 3.8–25.8; P = .01) and remained significant after adjusting for age, lean body mass, body mass index (BMI), and fat mass (all P ≤ .01). Every 500 fmol/punch increase in TFV-DP was associated with higher odds of reporting a fall in the prior 6 months (OR, 1.8; 95% CI, 1.1–2.8; P = .02); this remained significant after adjusting for age, lean body mass, BMI, and total fat mass (all P < .05). Conclusions Higher TFV-DP levels were associated with lower hip BMD, poorer physical function, and greater risk for falls, a concerning combination for increased fracture risk.

scholarly journals Tenofovir, Emtricitabine, and Tenofovir Diphosphate in Dried Blood Spots for Determining Recent and Cumulative Drug Exposure

2013 ◽  
Vol 29 (2) ◽  
pp. 384-390 ◽  
Author(s):  
Jose R. Castillo-Mancilla ◽  
Jia-Hua Zheng ◽  
Joseph E. Rower ◽  
Amie Meditz ◽  
Edward M. Gardner ◽  
...  
Keyword(s):  
Drug Exposure ◽  
Dried Blood Spots ◽  
Blood Spots ◽  
Tenofovir Diphosphate

scholarly journals Intracellular Tenofovir-Diphosphate and Emtricitabine-Triphosphate in Dried Blood Spots following Tenofovir Alafenamide

2020 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Jenna Yager ◽  
Jose Castillo-Mancilla ◽  
Mustafa E. Ibrahim ◽  
Kristina M. Brooks ◽  
Cricket McHugh ◽  
...  
Keyword(s):  
Dried Blood Spots ◽  
Blood Spots ◽  
Tenofovir Alafenamide ◽  
Tenofovir Diphosphate

scholarly journals Emtricitabine-Triphosphate in Dried Blood Spots as a Marker of Recent Dosing

2016 ◽  
Vol 60 (11) ◽  
pp. 6692-6697 ◽  
Author(s):  
Jose Castillo-Mancilla ◽  
Sharon Seifert ◽  
Kayla Campbell ◽  
Stacey Coleman ◽  
Kevin McAllister ◽  
...  
Keyword(s):  
Half Life ◽  
Dried Blood Spots ◽  
Directly Observed Therapy ◽  
Open Label ◽  
Limit Of Quantification ◽  
Antiretroviral Adherence ◽  
Blood Spots ◽  
Preexposure Prophylaxis ◽  
The Mean ◽  
Hiv Negative

ABSTRACTNew objective measures of antiretroviral adherence are needed. We determined if emtricitabine triphosphate (FTC-TP) in dried blood spots (DBS) can be used as a marker of recent dosing with tenofovir disoproxil fumarate-emtricitabine (TDF-FTC). The half-life of FTC-TP was estimated in DBS samples obtained from an intensive pharmacokinetic (PK) study of coformulated TDF-FTC in HIV-negative and HIV-infected participants. The concordance of quantifiable FTC-TP in DBS with tenofovir (TFV)/FTC in plasma was evaluated by utilizing paired plasma-DBS samples from participants enrolled in 2 large preexposure prophylaxis (PrEP) open-label trials. The time to FTC-TP nondetectability after TDF-FTC dosing was evaluated utilizing DBS from HIV-negative participants enrolled in a directly observed therapy study of variable adherence to TDF-FTC. The mean (95% confidence interval [CI]) terminal half-life of FTC-TP in the PK study was 35 (23 to 47) h. A total of 143/163 (88%) samples obtained 0 to 48 h post-TDF-FTC dose had quantifiable FTC-TP in DBS, compared with 2/93 (2%) and 0/87 (0%) obtained >48 and >96 h postdose. In 746 paired plasma-DBS samples from 445 participants enrolled in PrEP trials, when both TFV/FTC in plasma were below the limit of quantification, FTC-TP was as well in 98.9% of the samples, and when either TFV or FTC in plasma was quantifiable, FTC-TP was as well in 90.5% of the samples. The half-life of FTC-TP in DBS is short relative to that of TFV-diphosphate (TFV-DP), making it a surrogate for TFV-FTC detection in plasma. FTC-TP can be quantified in DBS simultaneously with TFV-DP, which quantifies cumulative adherence to TDF-FTC. (The clinical trials discussed in this article have been registered at ClinicalTrials.gov under identifiers NCT01040091, NCT02022657, NCT00458393, NCT01772823, and NCT02012621.)

scholarly journals Income Inequality Is Associated With Low Cumulative Antiretroviral Adherence in Persons With Human Immunodeficiency Virus

2020 ◽  
Vol 7 (10) ◽  
Author(s):  
Frances Vernon ◽  
Mary Morrow ◽  
Samantha MaWhinney ◽  
Ryan Coyle ◽  
Stacey Coleman ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Income Inequality ◽  
Gini Coefficient ◽  
Viral Suppression ◽  
Clinical Care ◽  
Dried Blood Spots ◽  
Antiretroviral Adherence ◽  
Blood Spots ◽  
Antiretroviral Drug ◽  
Immunodeficiency Virus

Abstract Background The adherence biomarker tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) is associated with viral suppression and predicts future viremia. However, its association with social determinants of health (SDoH) in people with human immunodeficiency virus (PWH) remains unknown. Methods Dried blood spots for TFV-DP were longitudinally collected from a clinical cohort of PWH receiving tenofovir disoproxil fumarate-based therapy (up to 3 visits over 48 weeks) residing in 5 Colorado counties. To assign SDoH, zip codes at enrollment were matched with SDoH data from AIDSVu (https://aidsvu.org/). The SDoH included household income, percentage living in poverty, education level, and income inequality (quantified using Gini coefficient, where 0 and 1 represent perfect income equality and inequality, respectively). Log-transformed TFV-DP concentrations were analyzed using a mixed-effects model to estimate percentage change (95% confidence interval) in TFV-DP for every significant change in the SDoH and adjusted for relevant covariates including age, gender, race, estimated glomerular filtration rate, body mass index, hematocrit, CD4+ T-cell count, antiretroviral drug class, and 3-month self-reported adherence. Results Data from 430 PWH totaling 950 person-visits were analyzed. In an adjusted analysis, income inequality was inversely associated with TFV-DP in DBS. For every 0.1 increase in the Gini coefficient, TFV-DP concentrations decreased by 9.2% (−0.5 to −17.1; P = .039). This remained significant after adjusting for human immunodeficiency virus viral suppression, where a 0.1 increase in Gini was associated with a decrease of 8.7% (−0.3 to −17.9; P = .042) in TFV-DP. Conclusions Higher income inequality was associated with lower cumulative antiretroviral adherence. These findings support the need for further research on how SDoH impact adherence and clinical care.

scholarly journals Application of an intracellular assay for determination of tenofovir-diphosphate and emtricitabine-triphosphate from erythrocytes using dried blood spots

2016 ◽  
Vol 122 ◽  
pp. 16-20 ◽  
Author(s):  
Jia-Hua Zheng ◽  
Caitlin Rower ◽  
Kevin McAllister ◽  
Jose Castillo-Mancilla ◽  
Brandon Klein ◽  
...  
Keyword(s):  
Dried Blood Spots ◽  
Blood Spots ◽  
Tenofovir Diphosphate

scholarly journals Intracellular Tenofovir-Diphosphate and Emtricitabine-Triphosphate in Dried Blood Spots following Directly Observed Therapy

2017 ◽  
Vol 62 (1) ◽  
Author(s):  
Peter L. Anderson ◽  
Albert Y. Liu ◽  
Jose R. Castillo-Mancilla ◽  
Edward M. Gardner ◽  
Sharon M. Seifert ◽  
...  
Keyword(s):  
Steady State ◽  
San Francisco ◽  
Dried Blood Spots ◽  
Directly Observed Therapy ◽  
Blood Spots ◽  
Preexposure Prophylaxis ◽  
Dosing Regimens ◽  
Sex With Men ◽  
Tenofovir Diphosphate ◽  
Dose Proportional

ABSTRACT Studies of daily emtricitabine-tenofovir disoproxil fumarate (FTC-TDF) for HIV preexposure prophylaxis (PrEP) in men who have sex with men (MSM) modeled intracellular tenofovir-diphosphate (TFV-DP) in dried blood spots (DBS) to assess adherence and corresponding PrEP outcomes. We conducted a prospective, randomized, crossover pharmacokinetic study of TFV-DP in DBS during 33%, 67%, or 100% of daily dosing under directly observed therapy (DOT). Participants were assigned to two 12-week dosing regimens, separated by a 12-week washout. Forty-eight adults (25 women) from Denver and San Francisco were included. TFV-DP exhibited a median half-life of 17 days, reaching steady state in 8 weeks. TFV-DP was dose proportional with mean (SD) steady-state concentrations of 530 (159), 997 (267), and 1,605 (405) fmol/punch for the 33%, 67%, and 100% arms, respectively. Prior work in MSM demonstrated clinically meaningful TFV-DP thresholds of 350, 700, and 1,250 fmol/punch, which were estimated 25th percentiles for 2, 4, and 7 doses/week. In the present study, corresponding TFV-DP was within 3% of the prior estimates, and subgroups by site, race, and sex were within 14% of prior estimates, although males had 17.6% (95% confidence intervals [CIs], 6.5, 27.4%) lower TFV-DP than females. The thresholds of 350, 700, and 1,250 fmol/punch were achieved by 75% of men taking ≥1.2, 3.2, and 6 doses/week and 75% of women taking ≥0.6, 2.0, and 5.3 doses/week, indicating that lower dosing reached these thresholds for both sexes. In conclusion, TFV-DP arising from DOT was similar to previous estimates and is useful for interpreting PrEP adherence and study outcomes. (This study has been registered at ClinicalTrials.gov under identifier NCT02022657.)

scholarly journals Factors associated with tenofovir diphosphate concentrations in dried blood spots in persons living with HIV

2020 ◽  
Vol 75 (6) ◽  
pp. 1591-1598 ◽  
Author(s):  
Ryan P Coyle ◽  
Mary Morrow ◽  
Stacey S Coleman ◽  
Edward M Gardner ◽  
Jia-Hua Zheng ◽  
...  
Keyword(s):  
Tenofovir Disoproxil Fumarate ◽  
Dried Blood Spots ◽  
Future Research ◽  
Art Adherence ◽  
Factors Associated ◽  
Blood Spots ◽  
Persons Living With Hiv ◽  
Clinical Covariates ◽  
Living With Hiv ◽  
Tenofovir Diphosphate

Abstract Objectives To determine factors associated with interindividual variability in tenofovir diphosphate (TFV-DP) concentrations in dried blood spots (DBSs) among persons living with HIV (PLWH). Methods PLWH who were at least 18 years old and taking tenofovir disoproxil fumarate-containing ART were prospectively recruited and enrolled from a clinical cohort and followed longitudinally (up to three visits over 48 weeks). With log-transformed TFV-DP concentrations in DBSs as the outcome, mixed-model regression analyses were used to assess associations between self-reported 3 month ART adherence, race and other clinical covariates (gender, age, BMI, CD4+ T cell count, estimated glomerular filtration rate, haematocrit, duration on current ART and anchor drug class) on TFV-DP in DBSs. Results Five hundred and twenty-seven participants (1150 person-visits) were analysed. Adjusting for race and other clinical covariates, every 10% increase in self-reported 3 month ART adherence was associated with an average TFV-DP concentration increase in DBSs of 28% (95% CI: 24%–32%; P < 0.0001). In the same model, female participants had 20% (95% CI: 3%–40%; P = 0.02) higher TFV-DP concentrations in DBSs, compared with male participants, and every 1 kg/m2 increase in BMI was associated with a decrease in TFV-DP concentration in DBSs by 2% (95% CI: −3% to −1%; P < 0.0001). Conclusions Individual patient characteristics were predictive of TFV-DP concentration in DBSs in PLWH receiving tenofovir disoproxil fumarate-based ART. Future research to incorporate these predictors into the interpretation of this ART adherence biomarker, and to establish whether these associations extend to PLWH taking tenofovir alafenamide-containing ART, is needed.

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