Clinical Pharmacology Quality Assurance for HIV and Related Infectious Diseases Research

DiFrancesco, Robin; Tooley, Kelly; Rosenkranz, Susan L.; Siminski, Susan; Taylor, Charlene R; Pande, Poonam; Morse, Gene D.

doi:10.1038/clpt.2013.62

Cited by 58 publications

(49 citation statements)

References 5 publications

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“…The assays for measuring TFV and FTC in hair samples in the HAL have been peer-reviewed and approved by the Division of AIDS’ Clinical Pharmacology and Quality Assurance (CPQA) program. [26] …”

Section: Methodsmentioning

confidence: 99%

Hair levels of preexposure prophylaxis drugs measure adherence and are associated with renal decline among men/transwomen

Gandhi¹,

Murnane

Bacchetti

et al. 2017

Aids

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Objective The U.S. PrEP Demonstration Project (Demo) evaluated men-who-have-sex-with-men on pre-exposure prophylaxis (PrEP) post-marketing and found low seroconversion rates. The objective of this study is to examine hair levels as an adherence measure to PrEP. Design Using an “opt-in” design, participants of PrEP Demo were invited to enroll into a substudy where hair was collected quarterly. Methods Tenofovir concentrations were measured in hair by liquid-chromatography/tandem-mass-spectrometry. Hair levels consistent with ≥4 doses per week (protective in other studies) defined adequate adherence. Mixed effects multivariate logistic regression models examined factors associated with ≥4 doses/week. Separate mixed effects models evaluated the relationship between hair PrEP levels and changes in creatinine clearance (CrCl) over time. Results Overall, 58% of Demo participants enrolled into this opt-in study; reasons for non-participation included insufficient hair (61%) and concerns about hairstyle (27%). Hair and DBS levels consistent with ≥4 doses/week were highly concordant (84%). Hair levels showed adequate adherence in 87% of 875 person-visits (among 280 participants). Factors associated with adequate adherence in multivariate models were amphetamine use (aOR 2.59 (0.97–6.9, p 0.06), condomless receptive anal sex (aOR 2.28 (1.19–4.40, p 0.01), and stable housing (aOR 2.63 (1.03–6.67), p 0.04). Hair levels of tenofovir showed a monotonic relationship with decline in CrCl (p 0.01 for trend). Conclusions In this substudy of the PrEP Demonstration Project, hair and DBS levels were highly concordant and hair concentrations demonstrated adequate adherence 87% of the time, with stable housing and high-risk behavior associated with higher adherence. Daily PrEP drug-taking is associated with modest declines in CrCl.

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Section: Methodsmentioning

confidence: 99%

Hair levels of preexposure prophylaxis drugs measure adherence and are associated with renal decline among men/transwomen

Gandhi¹,

Murnane

Bacchetti

et al. 2017

Aids

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“…21,48 Assays at UCSF have been developed and validated according to the principles of Good Laboratory Practices and some have undergone peer review and validation by the Division of AIDS Clinical Pharmacology and Quality Assurance (CPQA) program subsequent to the analysis of hair samples in this study. 49 This method has been validated from 0.05 to 20 ng/mg hair for EFV with good linearity (R 2 > 0.99) and reproducibility [coefficient of variation (CV) <15%]; interday and intraday assay precision was high (CV <15%), and accuracy ranged from 89% to 110% (M Gandhi and Y Huang, personal communication).…”

Section: Hair Specimen Processingmentioning

confidence: 99%

CYP2B66andCYP2B618Predict Long-Term Efavirenz Exposure Measured in Hair Samples in HIV-Positive South African Women

Röhrich

Drögemöller

Ikediobi

et al. 2016

AIDS Research and Human Retroviruses

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Long-term exposure to efavirenz (EFV) measured in hair samples may predict response to antiretroviral treatment (ART). Polymorphisms in CYP2B6 are known to alter EFV levels. The aim of this study was to assess the relationship between CYP2B6 genotype, EFV levels measured in hair, and virological outcomes on ART in a real-world setting. We measured EFV levels in hair from HIV-positive South African females who had been receiving EFV-based treatment for at least 3 months from the South African Black (SAB) (n = 81) and Cape Mixed Ancestry (CMA) (n = 53) populations. Common genetic variation in CYP2B6 was determined in 15 individuals from each population using bidirectional Sanger sequencing. Prioritized variants (n = 16) were subsequently genotyped in the entire patient cohort (n = 134). The predictive value of EFV levels in hair and selected variants in CYP2B6 on virological treatment outcomes was assessed. Previously described alleles (CYP2B6*2, CYP2B6*5, CYP2B6*6, CYP2B6*17, and CYP2B6*18), as well as two novel alleles (CYP2B6*31 and CYP2B6*32), were detected in this study. Compared to noncarriers, individuals homozygous for CYP2B6*6 had *109% increased EFV levels in hair ( p = .016) and CYP2B6*18 heterozygotes demonstrated 82% higher EFV hair levels ( p = .0006). This study confirmed that alleles affecting CYP2B6 metabolism and subsequent EFV exposure are present at significant frequencies in both the SAB and CMA populations. Furthermore, this study demonstrated that the use of hair samples for testing EFV concentrations may be a useful tool in determining long-term drug exposure in resource-limited countries.

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“…The laboratory’s hair assays for TFV and FTC have been peer-reviewed and approved by the Division of AIDS Clinical Pharmacology and Quality Assurance program 14 . Detailed methods for hair analyses have been previously described 8 .…”

Section: Methodsmentioning

confidence: 99%

Strong Correlation Between Concentrations of Antiretrovirals in Home-Collected and Study-Collected Hair Samples: Implications for Adherence Monitoring

Saberi

Neilands

Ming

et al. 2017

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Clinical Pharmacology Quality Assurance for HIV and Related Infectious Diseases Research

Cited by 58 publications

References 5 publications

Hair levels of preexposure prophylaxis drugs measure adherence and are associated with renal decline among men/transwomen

Hair levels of preexposure prophylaxis drugs measure adherence and are associated with renal decline among men/transwomen

CYP2B66andCYP2B618Predict Long-Term Efavirenz Exposure Measured in Hair Samples in HIV-Positive South African Women

Strong Correlation Between Concentrations of Antiretrovirals in Home-Collected and Study-Collected Hair Samples: Implications for Adherence Monitoring

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Clinical Pharmacology Quality Assurance for HIV and Related Infectious Diseases Research

Cited by 58 publications

References 5 publications

Hair levels of preexposure prophylaxis drugs measure adherence and are associated with renal decline among men/transwomen

Hair levels of preexposure prophylaxis drugs measure adherence and are associated with renal decline among men/transwomen

CYP2B6*6andCYP2B6*18Predict Long-Term Efavirenz Exposure Measured in Hair Samples in HIV-Positive South African Women

Strong Correlation Between Concentrations of Antiretrovirals in Home-Collected and Study-Collected Hair Samples: Implications for Adherence Monitoring

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Product

Resources

About

CYP2B66andCYP2B618Predict Long-Term Efavirenz Exposure Measured in Hair Samples in HIV-Positive South African Women