Brief Report: Adherence Biomarker Measurements in Older and Younger HIV-Infected Adults Receiving Tenofovir-Based Therapy

Seifert, Sharon M; Castillo‐Mancilla, José; Erlandson, Kristine M.; Morrow, Mary; Gandhi, Monica; Kuncze, Karen; Horng, Howard; Zheng, Jia‐Hua; Bushman, Lane R.; Kiser, Jennifer J.; MaWhinney, Samantha; Anderson, Peter L.

doi:10.1097/qai.0000000000001596

Cited by 23 publications

(12 citation statements)

References 22 publications

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“…The summary statistics of key characteristics of the included studies are presented in Table 2. In terms of the characteristics of ARV drugs, the included studies examined hair concentrations of 11 ARV drugs in four drug classes: nucleoside reverse transcriptase inhibitor (NRTI) including lamivudine (3TC) [24] , TFV [25][26][27][28][29][30][31][32][33][34] , and FTC [26,28,32] ; nonnucleoside reverse transcriptase inhibitor (NNRTI) including nevirapine (NVP) [35,36] , and efavirenz (EFV) [35,[37][38][39] ; protease inhibitor (PI) including indinavir (IDV) [40][41][42][43] , atazanavir (ATV) [35,[44][45][46][47] , lopinavir (LPV) [35,38,39,46,[48][49][50] , ritonavir (RTV) [35,38,46,50] , and darunavir (DRV) [47] ; and integrase strand transfer inhibitor (INSTI) including raltegravir (RAL) [47] . The included studies also reported a total of eight adhrences measures that were divided into three main categories including non-PK adherence measures (self-repo...…”

Section: Study Descriptionmentioning

confidence: 99%

Antiretroviral Concentration in Hair as a Measure for Antiretroviral Medication Adherence: A Systematic Review of Global Literature

et al. 2019

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This review aims to validate hair antiretroviral concentration (HAC) as a measure for antiretroviral medication adherence. This review included 31 studies that analyzed a total of 11 ARV drugs in four different drug classes. The associations between HAC and non-pharmacokinetic measures were generally lower than the association between HAC and other pharmacokinetic measures: the correlation coefficients (r) ranged from −0.20 to 0.38 for self-report or pill counts and 0.20 to 0.85 for electronic drug monitoring; HAC and other pharmacokinetic measures were positively correlated with the correlation coefficients (r) ranging from 0.20 to 0.72, 0.34 to 0.86, 0.50 to 0.85 for antiretroviral concentration in plasma, peripheral blood mononuclear cells, and dried blood spots, respectively. HAC was one of the strongest independent predictors of virologic responses. HAC of tenofovir was significantly associated with renal toxicity in large sample studies. This review suggests that HAC is a valid biomarker of antiretroviral medication adherence.

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Section: Study Descriptionmentioning

confidence: 99%

Antiretroviral Concentration in Hair as a Measure for Antiretroviral Medication Adherence: A Systematic Review of Global Literature

et al. 2019

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“…As far as we know, this was the first successful attempt to determine 2-OH NVP and 3-OH NVP and evaluate long-term adherence based on the concentrations of metabolites in human hair. Previous studies were limited to the detection of NVP metabolites in other biological samples, such as human serum [28] and for the adherence evaluation based on drug prototypes in hair [22][23][24][25]. Additionally, we found that NVP's metabolites showed high consistency with NVP in evaluating long-term adherence.…”

Section: Discussionmentioning

confidence: 78%

“…Existing studies utilize the concentrations of the drugs' prototype in hair to evaluate long-term adherence [22][23][24][25]. However, the antiretroviral drugs are mostly metabolized in the circulating system once orally administered and only a fraction of them remain as the prototype structure.…”

Section: Introductionmentioning

confidence: 99%

LC-MS/MS Quantification of Nevirapine and Its Metabolites in Hair for Assessing Long-Term Adherence

Yang

Chu

et al. 2020

Molecules

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The adherence assessment based on the combination of nevirapine (NVP) and its two metabolites (2-hydroxynevirapine and 3-hydroxynevirapine) would more comprehensively and accurately reflect long-term adherence than that of a single prototype. This study aimed to develop a specific, sensitive and selective method for simultaneous detection of the three compounds in hair and explore whether there was consistency among the three compounds in assessing long-term adherence. Furthermore, 75 HIV-positive patients who were taking the NVP drug were randomly recruited and divided into two groups (high-and low-adherence group). All participants self-reported their days of oral drug administration per month and provided their hair strands closest to the scalp at the region of posterior vertex. The concentrations of three compounds in the hair were determined using a developed LC-MS/MS method in multiple reaction monitoring. This method showed good performances in limit of quantification and accuracy with the recoveries from 85 to 115% and in precision with the intra-day and inter-day coefficients of variation within 15% for the three compounds. The population analysis revealed that patients with high-adherence showed significantly higher concentrations than those with low-adherence for all three compounds. There were significantly moderate correlations of nevirapine with 2-hydroxynevirapine and 3-hydroxynevirapin and high correlation between 2-hydroxynevirapine and 3-hydroxynevirapin. The two NVP’s metabolites showed high consistency with NVP in evaluating long-term adherence.

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“…Background regimen was divided by class, and protease inhibitors were further categorized to account for potentially increased TFVdp concentrations with specific protease inhibitors (atazanavir-ritonavir and lopinavir-ritonavir, compared with darunavirritonavir) (37,38). Race was included based on both literature from analyses of dried blood spots (42,43) and differences in the racial composition of the age groups. For continuous covariates, we used Akaike's Information Criterion and diagnostics of model fit to guide the choice of proper functional forms.…”

Section: Methodsmentioning

confidence: 99%

Intracellular Tenofovir and Emtricitabine Concentrations in Younger and Older Women with HIV Receiving Tenofovir Disoproxil Fumarate/Emtricitabine

Dumond

Bay

Nelson³

et al. 2020

Antimicrob Agents Chemother

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The altered immune states of aging and HIV infection may affect intracellular metabolism of tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC); increased cellular senescence decreases FTC-triphosphate (FTCtp) concentrations. The effects of age and inflammation on the ratio of intracellular metabolites (IM; tenofovir diphosphate [TFVdp], FTCtp) to their endogenous nucleotides (EN; dATP and dCTP, respectively), a potential treatment efficacy marker, was assessed among participants of the Women's Interagency HIV Study (WIHS), who ranged from 25-75 years. Samples from women receiving TDF/FTC with viral load <200 copies/mL were dichotomized by age at collection into two groups (≤45 years, ≥60 years). IM/EN concentrations were measured in peripheral blood mononuclear cell (PBMC) pellets; IL-6 and sCD163 were measured in plasma; senescent CD8+ T cells were measured in viable PBMCs. The TFVdp:dATP and FTCtp:dCTP ratios had statistically significantly different distributions in older and younger women (log-rank test p=0.0023 and p=0.032, respectively); in general, IM and EN concentrations were higher in the older women. After adjusting for potential confounders, these findings were not significant. In women ≤45 years, TFVdp was negatively associated with IL-6 and sCD163, while FTCtp was positively associated with sCD163 and IL-6 in women ≥60 years. BMI was positively associated with IL-6 in both age groups, and negatively associated with TFVdp in women ≤45 years. After adjustment, age remained significant for sCD163, while Black race, BMI, and renal function remained significant for several IMs and ENs, suggesting that factors associated with aging, but not age itself, govern intracellular TDF/FTC pharmacology.

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Brief Report: Adherence Biomarker Measurements in Older and Younger HIV-Infected Adults Receiving Tenofovir-Based Therapy

Abstract: Cumulative drug exposure measures (hair and DBS) were comparable in younger and older HIV-infected individuals on TFV-based therapy after adjustment for renal function.

Cited by 23 publications

References 22 publications

Antiretroviral Concentration in Hair as a Measure for Antiretroviral Medication Adherence: A Systematic Review of Global Literature

Antiretroviral Concentration in Hair as a Measure for Antiretroviral Medication Adherence: A Systematic Review of Global Literature

LC-MS/MS Quantification of Nevirapine and Its Metabolites in Hair for Assessing Long-Term Adherence

Intracellular Tenofovir and Emtricitabine Concentrations in Younger and Older Women with HIV Receiving Tenofovir Disoproxil Fumarate/Emtricitabine

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