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.

scholarly journals Moderately High Tenofovir Diphosphate in Dried Blood Spots Indicates Drug Resistance in Viremic Persons Living with HIV

2019 ◽  
Vol 18 ◽  
pp. 232595821988845 ◽  
Author(s):  
Jenna Lynn Yager ◽  
Ryan Patrick Coyle ◽  
Stacey Summer Coleman ◽  
Lucas Ellison ◽  
Jia-Hua Zheng ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Strong Predictor ◽  
Dried Blood Spots ◽  
Published Data ◽  
Virologic Suppression ◽  
Hiv Viral Load ◽  
Blood Spots ◽  
Persons Living With Hiv ◽  
Living With Hiv ◽  
Tenofovir Diphosphate

Background: Tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) is a strong predictor of viral suppression in persons living with HIV (PLWH). Its association with antiretroviral therapy (ART) resistance remains unknown. Methods: Blood was collected in PLWH receiving TDF-containing ART enrolled in a 48-week study. Tenofovir diphosphate/emtricitabine triphosphate (FTC-TP) were quantified from the same sample as HIV viral load (VL) in PLWH who developed resistance within ≤12 months. Results: The study enrolled 807 participants, of whom 10 had new resistance-conferring mutations. Among these, median (interquartile range) TFV-DP and HIV VL were 956 (407-1510) fmol/punch and 9840 (513-68,200) copies/mL, respectively. Five had quantifiable FTC-TP in DBS. Based on previously published data, a TFV-DP concentration of 956 fmol/punch would have an adjusted odds of virologic suppression of 32.8 versus TFV-DP <350 fmol/punch, making viremia of ∼10,000 copies/mL an unexpected outcome. Conclusion: Moderately high TFV-DP in DBS (700-1249 fmol/punch) in PLWH with high viremia suggest that antiretroviral drug resistance might be present.

scholarly journals Predictive Value of Tenofovir Diphosphate in Dried Blood Spots for Future Viremia in Persons Living With HIV

2019 ◽  
Vol 220 (4) ◽  
pp. 635-642 ◽  
Author(s):  
Mary Morrow ◽  
Samantha MaWhinney ◽  
Ryan P Coyle ◽  
Stacey S Coleman ◽  
Edward M Gardner ◽  
...  
Keyword(s):  
Viral Suppression ◽  
Prediction Models ◽  
Characteristic Curve ◽  
Dried Blood Spots ◽  
Blood Spots ◽  
Persons Living With Hiv ◽  
Receiver Operation Characteristic ◽  
Operation Characteristic ◽  
Living With Hiv ◽  
Tenofovir Diphosphate

AbstractBackgroundTenofovir diphosphate (TFV-DP) in dried blood spots (DBS) is associated with viral suppression in persons living with HIV (PLWH) taking tenofovir disoproxil fumarate (TDF). However, its value as a predictor of future viremia remained unknown.MethodsBlood for plasma viral load (VL) and TFV-DP in DBS were collected (up to 3 visits within 48 weeks) in PLWH on TDF. TFV-DP cut points were selected using logistic prediction models maximizing the area under the receiver operation characteristic curve, and estimated adjusted odds ratio (aOR) of future viremia (≥20 copies/mL) were compared to the highest TFV-DP category.ResultsAmong all 451 participants in the analysis, aOR of future viremia for participants with TFV-DP <800 and 800 to <1650 fmol/punch were 4.7 (95% CI, 2.6–8.7; P < .0001) and 2.1 (95% CI, 1.3–3.3; P = .002) versus ≥1650 fmol/punch, respectively. These remained significant for participants who were virologically suppressed at the time of the study visit (4.2; 95% CI, 1.5–12.0; P = .007 and 2.2; 95% CI, 1.2–4.0; P = .01).ConclusionsTFV-DP in DBS predicts future viremia in PLWH on TDF, even in those who are virologically suppressed. This highlights the utility of this biomarker to inform about adherence beyond VL.Clinical Trials Registration. NCT02012621.

scholarly journals Tenofovir Diphosphate in Dried Blood Spots Is Strongly Associated With Viral Suppression in Individuals With Human Immunodeficiency Virus Infections

2018 ◽  
Vol 68 (8) ◽  
pp. 1335-1342 ◽  
Author(s):  
Jose R Castillo-Mancilla ◽  
Mary Morrow ◽  
Ryan P Coyle ◽  
Stacey S Coleman ◽  
Edward M Gardner ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Viral Suppression ◽  
Geometric Mean ◽  
Dried Blood Spots ◽  
Hiv Treatment ◽  
Virologic Suppression ◽  
Blood Spots ◽  
Persons Living With Hiv ◽  
Immunodeficiency Virus ◽  
Tenofovir Diphosphate

Abstract Background Although tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) is a predictor of adherence and pre-exposure prophylaxis efficacy, its utility in human immunodeficiency virus (HIV) treatment remains unknown. Methods DBS for TFV-DP were collected up to 3 times over 48 weeks in persons living with HIV (PLWH) who were receiving TFV disoproxil fumarate (TDF)-based therapy. Log-transformed baseline TFV-DP was compared using t-tests or analyses of variance; generalized estimating equations were used to estimate the adjusted odds ratio (aOR) of viral suppression (&lt;20 copies/mL) based on the TFV-DP concentration at the study visit. Results We analyzed 1199 DBS from 532 participants (76 female; 101 Black, 101 Hispanic). Among the virologically-suppressed participants at baseline (n = 347), TFV-DP was lower in Blacks (geometric mean 1453, 95% confidence interval [CI] 1291–1635) vs Whites (1793, 95% CI 1678–1916; P = .002) and Hispanics (1760, 95% CI 1563–1982; P = .025); in non-boosted (1610, 95% CI 1505–1723) vs. boosted (1888, 95% CI 1749–2037; P = .002) regimens; and in non-nucleoside reverse transcription inhibitor–based (1563, 95% CI 1432–1707) vs. boosted protease inhibitor–based (1890, 95% CI 1704–2095; P = .006) and multiclass-based (1927, 95% CI 1650–2252; P = .022) regimens. The aOR of virologic suppression, after adjusting for age, gender, race, body mass index, estimated glomerular filtration rate, CD4+ T-cell count, antiretroviral drug class and duration of therapy, was 73.5 (95% CI 25.7–210.5; P &lt; .0001) for a TFV-DP concentration ≥1850 fmol/punch compared to &lt;350 fmol/punch. Conclusions TFV-DP in DBS is strongly associated with virologic suppression in PLWH on TDF-based therapy and is associated with certain participant characteristics. Further research is required to evaluate this drug adherence and exposure measure in clinical practice. Clinical Trials Registration NCT02012621.

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 &lt; .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

Factors Associated with Sexual Risk Behavior Among Persons Living with HIV: Gender and Sexual Identity Group Differences

2007 ◽  
Vol 12 (5) ◽  
pp. 685-694 ◽  
Author(s):  
Cari Courtenay-Quirk ◽  
Sherri L. Pals ◽  
Grant Colfax ◽  
David McKirnan ◽  
Lauren Gooden ◽  
...  
Keyword(s):  
Sexual Identity ◽  
Risk Behavior ◽  
Sexual Risk ◽  
Sexual Risk Behavior ◽  
Group Differences ◽  
Factors Associated ◽  
Identity Group ◽  
Persons Living With Hiv ◽  
Living With Hiv

scholarly journals Intersectionality and Cognitive Impairment Risk in Older Persons With HIV: Age, Ethnicity, and LGBT Status

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 724-724
Author(s):  
Monica Rivera Mindt ◽  
Micah Savin ◽  
Angela Summers ◽  
Jordan Stiver ◽  
Alex Slaughter
Keyword(s):  
Working Memory ◽  
Cognitive Impairment ◽  
Executive Functioning ◽  
Hiv Infection ◽  
Older Persons ◽  
Neurocognitive Impairment ◽  
Future Research ◽  
Multiple Regressions ◽  
Persons Living With Hiv ◽  
Living With Hiv

Abstract The Latinx population is disproportionately affected by HIV-infection and older Latinx persons living with HIV (PLWH) are at greater risk for neurocognitive impairment (NCI). However, no studies have examined whether intersectionality (including Lesbian Gay Bisexual Transgender [LGBT] status) increases NCI risk. This study investigated whether LGBT status increases NCI risk in 126 PLWH (Ages 19-73 years; 74% Male; 66% Latinx, 34% NHW) who completed a comprehensive NC battery. Domain average T-scores were based on demographically-corrected norms. Multiple regressions revealed that after accounting for covariates (cocaine use, premorbid IQ) and other dimensions of intersectionality (age, ethnicity), LGBT status significantly contributed to NCI risk in attention/working memory (B=-4.50, p=.01) and executive functioning (trend-level; B=-3.67, p=.06). LGBT status, a key dimension of intersectionality, should be considered in NC assessment of PLWH. Future research is needed to identify factors (e.g., discrimination) that may confer increased NCI risk in this population.

Mapping Evidence Of Patient-centered Care For Persons Living With Hiv: A Protocol For A Systematic Scoping Review

2019 ◽  
Author(s):  
Delarise Mulqueeny ◽  
Manduleli Herald Pokiya ◽  
Praba Naidoo
Keyword(s):  
Scoping Review ◽  
Grey Literature ◽  
Hiv Treatment ◽  
World Health ◽  
Hiv Care ◽  
Future Research ◽  
Clinical Settings ◽  
Keywords Hiv ◽  
Persons Living With Hiv ◽  
Living With Hiv

Abstract Background: The Human Immunodeficiency virus (HIV) is a global, chronic health challenge that warrants a multidimensional approach to treatment and care. Notwithstanding the strides made in suppressing the virus, evidence illustrates challenges in persons living with HIV (PLHIV) experiences of treatment and care. Such experiences threaten HIV patients’ retention, adherence, mortality, comorbidities and the global community’s efforts to end the AIDS epidemic by 2030. A patient-centred approach (PCC) to HIV care and treatment could improve patients’ health care experiences, wellbeing, retention and adherence and strengthen patient-provider relationships, Hence, the aim of this scoping review is to comprehensively map existing evidence of PCC in HIV treatment and care. Additionally, the review will identify and describe gaps that could inform future research and interventional programmes or the need for systematic reviews. Methods and analysis: As HIV PCC is a broad topic, a systematic scoping review, that includes peer-reviewed journal articles and grey literature will be conducted. Online databases: (Google scholar, Scopus, EBSCOhost, PsycINFO via ProQuest, PsycARTICLES via ProQuest, International Bibliography of the Social Sciences (IBSS) via ProQuest, UNAIDS databases will be accessed. Humanitarian databases such as the World Health Organization (WHO) and United Nations Educational, Scientific and Cultural Organization (UNESCO) will also be accessed to identify literature on PCC for PLHIV. Such literature will be published between 2009 and 2019. Two reviewers will independently extract data from relevant search engines, utilising specific inclusion and exclusion standards. Thereafter thematic content analysis will be performed, and a narrative account of the findings will be presented. Discussion: As this is a scoping review, no ethical approval is required. Once the review is completed all summarized data will be disseminated in peer-reviewed journals, at national and international conferences, clinical settings and to policy makers. This is aimed at improving PLHIV’s experiences in clinical settings, practice and care. Keywords: HIV, patient-centred care, patient experiences, ART programme; ARVS; patients

scholarly journals Increased tenofovir monoester concentrations in patients receiving tenofovir disoproxil fumarate with ledipasvir/sofosbuvir

2019 ◽  
Vol 74 (8) ◽  
pp. 2360-2364 ◽  
Author(s):  
Kristina M Brooks ◽  
Jose R Castillo-Mancilla ◽  
Joshua Blum ◽  
Ryan Huntley ◽  
Samantha MaWhinney ◽  
...  
Keyword(s):  
Tenofovir Disoproxil Fumarate ◽  
Clinical Relevance ◽  
Geometric Mean ◽  
Plasma Concentrations ◽  
Dried Blood Spots ◽  
Pharmacokinetic Parameters ◽  
Post Dose ◽  
P Values ◽  
Hydrolysis Of ◽  
Tenofovir Diphosphate

AbstractBackgroundIntracellular tenofovir diphosphate concentrations are markedly increased in HIV/HCV coinfected individuals receiving tenofovir disoproxil fumarate (TDF) with sofosbuvir-containing treatment. Sofosbuvir may inhibit the hydrolysis of TDF to tenofovir, resulting in increased concentrations of the disoproxil or monoester forms, which may augment cell loading. We sought to quantify tenofovir disoproxil and monoester concentrations in individuals receiving TDF with and without ledipasvir/sofosbuvir.MethodsHIV/HCV coinfected participants receiving TDF-based therapy were sampled pre-dose and 1 and 4 h post-dose prior to and 4 weeks after initiating ledipasvir/sofosbuvir. Tenofovir disoproxil was not detectable. Tenofovir monoester in plasma and tenofovir diphosphate in PBMC and dried blood spots (DBS) were quantified using LC-MS/MS. Geometric mean ratios (week 4 versus baseline) and 95% CIs were generated for the pharmacokinetic parameters. P values reflect paired t-tests.ResultsTen participants had complete data. At baseline, geometric mean (95% CI) tenofovir monoester plasma concentrations at 1 and 4 h post-dose were 97.4 ng/mL (33.0–287.5) and 0.74 ng/mL (0.27–2.06), respectively. With ledipasvir/sofosbuvir, tenofovir monoester concentrations at 4 h post-dose were 5.02-fold higher (95% CI 1.40–18.05; P = 0.019), but did not significantly differ at 1 h post-dose (1.72-fold higher, 95% CI 0.25–11.78; P = 0.54), possibly due to absorption variability. Tenofovir diphosphate in PBMC and DBS were increased 2.80-fold (95% CI 1.71–4.57; P = 0.001) and 7.31-fold (95% CI 4.47–11.95; P < 0.0001), respectively, after 4 weeks of ledipasvir/sofosbuvir.ConclusionsTenofovir monoester concentrations were increased in individuals receiving TDF with ledipasvir/sofosbuvir, consistent with inhibition of TDF hydrolysis. Additional studies are needed to determine the clinical relevance of this interaction.

Sign in / Sign up

Export Citation Format

Share Document