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 (<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 < .0001) for a TFV-DP concentration ≥1850 fmol/punch compared to <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 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 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 Frequency and Predictors of Tenofovir-diphosphate Detection Among Young Kenyan Women in a Real-world Pre-exposure Prophylaxis Implementation Program

2020 ◽  
Vol 71 (9) ◽  
pp. e509-e512 ◽  
Author(s):  
Jillian Pintye ◽  
John Kinuthia ◽  
Felix Abuna ◽  
Kenneth Mugwanya ◽  
Harison Lagat ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Real World ◽  
Dried Blood Spots ◽  
Blood Spots ◽  
Implementation Program ◽  
Immunodeficiency Virus ◽  
Kenyan Women ◽  
Exposure Prophylaxis ◽  
Tenofovir Diphosphate

Abstract In a pre-exposure prophylaxis program for Kenyan women, we detected tenofovir-diphosphate in 61% (125/201) of randomly selected dried blood spots collected at the first follow-up visit. Tenofovir-diphosphate was detected more frequently among women who had partners living with human immunodeficiency virus, who were not pregnant, and who were ≥24 years.

scholarly journals Coadministration of Indinavir and Nelfinavir in Human Immunodeficiency Virus Type 1-Infected Adults: Safety, Pharmacokinetics, and Antiretroviral Activity

2002 ◽  
Vol 46 (12) ◽  
pp. 3877-3882 ◽  
Author(s):  
Sharon A. Riddler ◽  
Diane Havlir ◽  
Kathleen E. Squires ◽  
Brad Kerr ◽  
Ronald H. Lewis ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Geometric Mean ◽  
Pharmacokinetic Profile ◽  
Pharmacokinetic Data ◽  
Virologic Suppression ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Combinations of protease inhibitors (PIs) can have potentially beneficial pharmacokinetic interactions, resulting in higher drug levels and less frequent dose administration. Indinavir (IDV) and nelfinavir (NFV) are potent inhibitors of human immunodeficiency virus type 1 (HIV-1) protease and are commonly prescribed antiretroviral agents. Pilot pharmacokinetic data suggested a bidirectional enhancing interaction between IDV and NFV. A phase II study was conducted to evaluate the safety, pharmacokinetics, and antiviral activity of IDV plus NFV given in a combination every 12 h in HIV-1-infected subjects. IDV plus NFV was given as a twice-daily regimen to 20 HIV-1-infected subjects who were PI naive (11 of 20 were antiretroviral naive). After week 18, nucleoside reverse transcriptase inhibitors were added to the treatment regimen in seven subjects. The enrolled subjects had a geometric mean baseline plasma HIV-1 RNA of 63,095 copies/ml and a mean CD4+ cell count of 266 cells/mm3. Pharmacokinetic evaluations were performed at the following doses: IDV at 1,000 mg every 12 h (q12h) plus NFV at 750 mg q12h, IDV at 1,000 mg q12h plus NFV at 1,000 mg q12h, and IDV at 1,200 mg q12h plus NFV at 1,250 mg q12h. The coadministration of IDV plus NFV resulted in a modest inhibition of IDV elimination, resulting in a plasma profile of IDV 1200 mg q12h (with NFV at 1,250 mg q12h) that was comparable to the standard IDV dose of 800 mg q8h. In contrast, IDV had no apparent effect on the pharmacokinetic profile of NFV. The combination of IDV and NFV was generally well tolerated and resulted in sustained virologic suppression with 45% of the subjects having an HIV-1 RNA level in plasma of <400 copies/ml at week 72 (intent-to-treat).

scholarly journals Degree of Housing Instability Shows Independent “Dose-Response” With Virologic Suppression Rates Among People Living With Human Immunodeficiency Virus

2018 ◽  
Vol 5 (3) ◽  
Author(s):  
Angelo Clemenzi-Allen ◽  
Elvin Geng ◽  
Katerina Christopoulos ◽  
Hali Hammer ◽  
Susan Buchbinder ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Dose Response ◽  
Living Arrangements ◽  
Viral Suppression ◽  
Housing Instability ◽  
Virologic Suppression ◽  
Inverse Association ◽  
Housing Status ◽  
Immunodeficiency Virus ◽  
Strong Inverse Association

Abstract Housing instability negatively impacts outcomes in people living with human immunodeficiency virus (PLHIV), yet the effect of diverse living arrangements has not previously been evaluated. Using 6 dwelling types to measure housing status, we found a strong inverse association between housing instability and viral suppression across a spectrum of unstable housing arrangements.

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