RESUMO
Liposils, synthesized via the liposome templating method, offer a promising strategy for enhancing liposome stability by employing a silica coating. This study focuses on the development of nanocarriers utilizing silica-coated nanoliposomes for encapsulating the poorly water-soluble drug, ibrutinib. Ibrutinib-loaded nanoliposomes were meticulously formulated using the reverse-phase evaporation technique, serving as templates for silica coating, resulting in spherical liposils with an average size of approximately 240 nanometers. Comprehensive characterization of the liposil's physical and chemical properties was conducted using various analytical methods, including dynamic light scattering, transmission electron microscopy, Fourier-transform infrared spectroscopy, and X-ray diffraction analysis. Liposils demonstrated superior performance compared to ibrutinib-loaded nanoliposomes, showing sustained drug release profiles in simulated intestinal fluids and resistance to simulated gastric fluid, as confirmed by dissolution studies. Moreover, ibrutinib liposils exhibited a significant increase in half-life (4.08-fold) and notable improvement in bioavailability (3.12-fold) compared to ibrutinib suspensions, as determined by pharmacokinetic studies in rats. These findings underscore the potential of liposils as nanocarriers for orally delivering poorly water-soluble drugs, offering enhanced stability and controlled release profiles, thereby improving bioavailability prospects and therapeutic efficacy. This approach holds promise for addressing challenges associated with the oral administration of drugs with limited solubility, thereby advancing drug delivery technologies and clinical outcomes in pharmaceutical research and development.
Assuntos
Adenina , Disponibilidade Biológica , Lipossomos , Piperidinas , Pirazóis , Pirimidinas , Adenina/farmacocinética , Adenina/análogos & derivados , Adenina/administração & dosagem , Adenina/química , Piperidinas/farmacocinética , Piperidinas/administração & dosagem , Piperidinas/química , Animais , Administração Oral , Lipossomos/química , Pirimidinas/farmacocinética , Pirimidinas/administração & dosagem , Pirimidinas/química , Ratos , Pirazóis/farmacocinética , Pirazóis/administração & dosagem , Pirazóis/química , Masculino , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Nanopartículas/química , Ratos Sprague-Dawley , Dióxido de Silício/químicaRESUMO
ZCL-278 is a selective small molecule specifically inhibiting the Cdc42-intersectin interaction, yet its in-vivo pharmacokinetic and pharmacodynamic properties against renal diseases had not been determined. Thus, our study explored the absorption, distribution and excretion of ZCL-278 as well as its pharmacological efficacy against chronic kidney disease (CKD). With the optimized detection method, absolute oral bioavailability of ZCL-278 was determined as 10.99â¯% in male and 17.34â¯% in female rats. ZCL-278 was rapidly and abundantly distributed in various tissues, especially the kidney and heart, while few excreted through urine and feces. In the adenine-induced CKD mice, the increased plasma creatinine and urea, the decreased body weight as well as the renal pathological alterations, including vacuolization of renal tubular epithelial cells, granular degeneration, cell flattening, luminal dilation, and cylindruria, were significantly ameliorated after ZCL-278 administration. Moreover, ZCL-278 could also reverse the increased intensities of renal inflammation and fibrosis in the CKD mice. These results clarified the pharmacokinetics of ZCL-278 in rats and preliminarily indicated that ZCL-278 has favorable pharmacodynamic properties for CKD primed for lead development and optimization, warranting further drug development.
Assuntos
Ratos Sprague-Dawley , Insuficiência Renal Crônica , Animais , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/metabolismo , Masculino , Feminino , Camundongos , Ratos , Adenina/farmacocinética , Adenina/análogos & derivados , Distribuição Tecidual , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Disponibilidade BiológicaRESUMO
We characterized population pharmacokinetics in 42 African children receiving once-daily 25 mg (14 to <20 kg) or 50 mg (>20 kg) dolutegravir. Coadministration with emtricitabine and tenofovir alafenamide reduced dolutegravir bioavailability by 19.6% (95% confidence interval: 8.13%-30.8%) compared with zidovudine or abacavir with lamivudine. Nevertheless, concentrations remained above efficacy targets, confirming current dosing recommendations.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Compostos Heterocíclicos com 3 Anéis , Oxazinas , Piperazinas , Piridonas , Humanos , Piridonas/farmacocinética , Compostos Heterocíclicos com 3 Anéis/farmacocinética , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/sangue , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Oxazinas/farmacocinética , Piperazinas/farmacocinética , Infecções por HIV/tratamento farmacológico , Criança , Masculino , Feminino , Fármacos Anti-HIV/farmacocinética , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/sangue , Fármacos Anti-HIV/administração & dosagem , Tenofovir/farmacocinética , Tenofovir/uso terapêutico , Pré-Escolar , Adolescente , Emtricitabina/farmacocinética , Emtricitabina/uso terapêutico , Emtricitabina/administração & dosagem , Didesoxinucleosídeos/farmacocinética , Didesoxinucleosídeos/uso terapêutico , Didesoxinucleosídeos/administração & dosagem , Lamivudina/farmacocinética , Lamivudina/uso terapêutico , Lamivudina/administração & dosagem , Inibidores de Integrase de HIV/farmacocinética , Inibidores de Integrase de HIV/uso terapêutico , Inibidores de Integrase de HIV/administração & dosagem , Alanina/farmacocinética , Alanina/análogos & derivados , Alanina/uso terapêutico , Disponibilidade Biológica , Quimioterapia Combinada , Zidovudina/farmacocinética , Zidovudina/uso terapêutico , Zidovudina/administração & dosagem , Adenina/análogos & derivados , Adenina/farmacocinética , Adenina/uso terapêutico , Interações MedicamentosasRESUMO
The nucleos(t)ide analogs require phosphorylation to the pharmacologically active anabolites in cells. We investigated the hypothesis that single-nucleotide polymorphisms (SNPs) in genes that encode transporters and phosphodiesterase (PDE) enzymes involved in tenofovir (TFV), disoproxil fumarate (TDF), and lamivudine (3TC) disposition will be associated with concentrations of their phosphate anabolites and virologic response. Individuals with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) coinfection receiving TDF/3TC-containing antiretroviral therapy were enrolled. Steady-state TFV diphosphate (TFV-DP) and 3TC triphosphate (3TC-TP) concentrations in peripheral blood mononuclear cells (PBMCs) and dried blood spot samples were quantified. The relationship between genetic variants and TFV-DP and 3TC-TP concentrations as well as with virologic response were examined using multivariable linear regression. Of the 136 participants (median age 43 years; 63% females), 6.6% had HBV non-suppression, and 7.4% had HIV non-suppression. The multidrug resistance protein 2 (encoded by ABCC2 rs2273697) SNP was associated with 3TC-TP concentrations in PBMCs. The human organic anion transporter-1 (encoded by SLC28A2) rs11854484 SNP was associated with HIV non-suppression, and when evaluated together with SNPs with marginal associations (ABCC2 rs717620 and PDE1C rs30561), participants with two or three variants compared to those with none of these variants had an adjusted odds ratio of 48.3 (confidence interval, 4.3-547.8) for HIV non-suppression. None of the SNPs were associated with HBV non-suppression. Our study identified ABCC2 SNP to be associated with 3TC-TP concentrations in PBMCs. Also, a combination of genetic variants of drug transporters and PDE was associated with HIV non-suppression.
Assuntos
Fármacos Anti-HIV , Coinfecção , Infecções por HIV , Lamivudina , Proteína 2 Associada à Farmacorresistência Múltipla , Proteínas Associadas à Resistência a Múltiplos Medicamentos , Polimorfismo de Nucleotídeo Único , Tenofovir , Humanos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/genética , Feminino , Masculino , Adulto , Lamivudina/uso terapêutico , Polimorfismo de Nucleotídeo Único/genética , Tenofovir/uso terapêutico , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Fármacos Anti-HIV/uso terapêutico , Fármacos Anti-HIV/farmacocinética , Pessoa de Meia-Idade , Coinfecção/tratamento farmacológico , Coinfecção/genética , Leucócitos Mononucleares/metabolismo , Vírus da Hepatite B/genética , Vírus da Hepatite B/efeitos dos fármacos , Organofosfatos/uso terapêutico , Organofosfatos/farmacocinética , Hepatite B/tratamento farmacológico , Hepatite B/genética , Adenina/análogos & derivados , Adenina/uso terapêutico , Adenina/farmacocinética , Polifosfatos/metabolismo , Farmacogenética/métodosRESUMO
AIMS: Trans/transfeminine women are disproportionally affected by HIV. Concerns regarding negative drug-drug interactions (DDIs) between ART drugs and gender-affirming hormone therapy (GAHT), specifically feminizing hormone therapy (FHT), may contribute to the lower ART uptake by trans women with HIV compared with their cis counterparts. The aim of this study is to investigate the bidirectional pharmacokinetic effects of components of FHT regimens (oral oestradiol and androgen-suppressing medications) with the ART regimen (bictegravir/emtricitabine/tenofovir alafenamide [B/F/TAF)]. METHODS: We present a protocol for a three-armed, parallel-group, longitudinal (6-month), DDI study. Group 1 includes 15 3trans women with HIV taking FHT and ART; group 2 includes 15 premenopausal cis women with HIV taking ART; group 3 includes 15 trans women without HIV taking FHT. Women with HIV must be on or switch to B/F/TAF at baseline and be virally suppressed for ≥3 months. Trans women must be taking a stable regimen of ≥2 mg daily oral oestradiol and an anti-androgen (pharmaceutical, and/or surgical, and/or medical) for ≥3 months. Plasma ART drug concentrations will be sampled at Month 2 and compared between groups 1 and 2. Serum oestradiol concentrations will be sampled at baseline and Month 2 visits and compared between groups 1 and 3. The primary outcomes are B/F/TAF pharmacokinetic parameters (Cmin, Cmax and AUC) and oestradiol concentrations (Cmin, C4h, Cmax and AUC) at month 2. DISCUSSION: This study is of global importance as it provides critical information regarding safe coadministration of B/F/TAF and FHT, both of which are life-saving therapies for trans women with HIV.
Assuntos
Adenina , Fármacos Anti-HIV , Interações Medicamentosas , Emtricitabina , Estradiol , Infecções por HIV , Piperazinas , Tenofovir , Pessoas Transgênero , Humanos , Feminino , Infecções por HIV/tratamento farmacológico , Emtricitabina/farmacocinética , Emtricitabina/administração & dosagem , Tenofovir/farmacocinética , Tenofovir/administração & dosagem , Tenofovir/análogos & derivados , Fármacos Anti-HIV/farmacocinética , Fármacos Anti-HIV/administração & dosagem , Estradiol/administração & dosagem , Estradiol/sangue , Estradiol/farmacocinética , Piperazinas/administração & dosagem , Piperazinas/farmacocinética , Adulto , Adenina/análogos & derivados , Adenina/farmacocinética , Adenina/administração & dosagem , Compostos Heterocíclicos de 4 ou mais Anéis/farmacocinética , Compostos Heterocíclicos de 4 ou mais Anéis/administração & dosagem , Alanina/farmacocinética , Alanina/administração & dosagem , Piridonas/administração & dosagem , Piridonas/farmacocinética , Estudos Longitudinais , Combinação de Medicamentos , Antagonistas de Androgênios/farmacocinética , Antagonistas de Androgênios/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/farmacocinética , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Pessoa de Meia-Idade , Adulto Jovem , Amidas/farmacocinética , Amidas/administração & dosagemRESUMO
Ibrutinib, an antineoplastic agent tackling chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom's Macroglobulinemia, falls under the category of BCS class II drugs, characterized by a puzzling combination of low solubility and high permeability. Its oral bioavailability remains a perplexing challenge, merely reaching 2.9 % due to formidable first-pass metabolism hurdles. In a bid to surmount this obstacle, researchers embarked on a journey to develop ibrutinib-loaded NLCs (Nanostructured Lipid Carriers) using a methodology steeped in complexity: a Design of Experiments (DoE)-based hot melted ultrasonication approach. Despite a plethora of methods for analyzing ibrutinib in various matrices, the absence of a spectrofluorimetric method for assessing it in rat plasma added to the enigma. Thus emerged a spectrofluorimetric method, embodying principles of white analytical chemistry and analytical quality by design, employing a Placket-Burman design for initial method exploration and a central composite design for subsequent refinement. This method underwent rigorous validation in accordance with ICH guidelines, paving the way for its application in scrutinizing the in-vivo pharmacokinetics of ibrutinib-loaded NLCs, juxtaposed against commercially available formulations. Surprisingly, the optimized NLCs exhibited a striking 1.82-fold boost in oral bioavailability, shedding light on their potential efficacy. The environmental impact of this method was scrutinized using analytical greenness tools, affirming its eco-friendly attributes. In essence, the culmination of these efforts has not only propelled advancements in drug bioavailability but also heralded the dawn of a streamlined and environmentally conscious analytical paradigm.
Assuntos
Adenina , Lipídeos , Piperidinas , Pirimidinas , Espectrometria de Fluorescência , Animais , Adenina/análogos & derivados , Adenina/farmacocinética , Adenina/química , Adenina/sangue , Piperidinas/farmacocinética , Piperidinas/química , Piperidinas/sangue , Lipídeos/química , Masculino , Espectrometria de Fluorescência/métodos , Ratos , Pirimidinas/farmacocinética , Pirimidinas/química , Pirimidinas/sangue , Portadores de Fármacos/química , Nanoestruturas/química , Pirazóis/farmacocinética , Pirazóis/química , Pirazóis/sangue , Pirazóis/administração & dosagem , Reprodutibilidade dos Testes , Ratos WistarRESUMO
Human immunodeficiency virus (HIV) continues to pose a serious threat to global health. Oral preexposure prophylaxis (PrEP), considered highly effective for HIV prevention, is the utilisation of antiretroviral (ARV) drugs before HIV exposure in high-risk uninfected individuals. However, ARV drugs are associated with poor patient compliance and pill fatigue due to their daily oral dosing. Therefore, an alternative strategy for drug delivery is required. In this work, two dissolving microneedle patches (MNs) containing either bictegravir (BIC) or tenofovir alafenamide (TAF) solid drug nanoparticles (SDNs) were developed for systemic delivery of a novel ARV regimen for potential HIV prevention. According to ex vivo skin deposition studies, approximately 11% and 50% of BIC and TAF was delivered using dissolving MNs, respectively. Pharmacokinetic studies in Sprague Dawley rats demonstrated that BIC MNs achieved a long-acting release profile, maintaining the relative plasma concentration above the 95% inhibitory concentration (IC95) for 3 weeks. For TAF MNs, a rapid release of drug and metabolism of TAF into TFV were obtained from the plasma samples. This work has shown that the proposed transdermal drug delivery platform could be potentially used as an alternative method to systemically deliver ARV drugs for HIV PrEP.
Assuntos
Administração Cutânea , Alanina , Fármacos Anti-HIV , Infecções por HIV , Agulhas , Profilaxia Pré-Exposição , Ratos Sprague-Dawley , Tenofovir , Animais , Tenofovir/administração & dosagem , Tenofovir/farmacocinética , Tenofovir/análogos & derivados , Alanina/farmacocinética , Alanina/administração & dosagem , Alanina/química , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/farmacocinética , Profilaxia Pré-Exposição/métodos , Infecções por HIV/prevenção & controle , Masculino , Adenina/administração & dosagem , Adenina/farmacocinética , Adenina/análogos & derivados , Adenina/química , Ratos , Nanopartículas/administração & dosagem , Nanopartículas/química , Liberação Controlada de Fármacos , Compostos Heterocíclicos de 4 ou mais Anéis/farmacocinética , Compostos Heterocíclicos de 4 ou mais Anéis/administração & dosagem , Compostos Heterocíclicos de 4 ou mais Anéis/química , Piridonas/administração & dosagem , Piridonas/farmacocinética , Sistemas de Liberação de Medicamentos , Piperazinas/farmacocinética , Piperazinas/administração & dosagem , Piperazinas/química , Ciclopropanos/administração & dosagem , Ciclopropanos/farmacocinética , Compostos Heterocíclicos com 3 Anéis/farmacocinética , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Amidas/administração & dosagem , Amidas/farmacocinética , Amidas/químicaRESUMO
We evaluated hair tenofovir (TFV) concentrations as an adherence metric for HIV preexposure prophylaxis during pregnancy and postpartum and compared hair levels with TFV-diphosphate levels in dried blood spots (DBSs). Overall 152 hair samples from 102 women and 36 hair-DBS paired samples from 29 women were collected from a subset of women in a cluster-randomized trial. Having a partner with HIV was associated with higher hair TFV levels (P < .001). Hair TFV concentrations were strongly correlated with DBS TFV-diphosphate levels (r = 0.76, P < .001), indicating hair as a promising cumulative adherence metric for perinatal preexposure prophylaxis assessment.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Cabelo , Período Pós-Parto , Profilaxia Pré-Exposição , Tenofovir , Humanos , Feminino , Gravidez , Cabelo/química , Infecções por HIV/prevenção & controle , Adulto , Fármacos Anti-HIV/farmacocinética , Fármacos Anti-HIV/sangue , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Tenofovir/farmacocinética , Tenofovir/administração & dosagem , Tenofovir/sangue , Tenofovir/uso terapêutico , Teste em Amostras de Sangue Seco/métodos , Adesão à Medicação/estatística & dados numéricos , Complicações Infecciosas na Gravidez/prevenção & controle , Complicações Infecciosas na Gravidez/tratamento farmacológico , Adulto Jovem , Adenina/análogos & derivados , Adenina/uso terapêutico , Adenina/administração & dosagem , Adenina/farmacocinética , Adenina/sangue , OrganofosfatosRESUMO
Tenofovir alafenamide (TAF) is a BCS Class III compound and an oral pro-drug of Tenofovir (TFV) with limited oral bioavailability. The bioavailability of the oral intake increases with food as a result of the low stability of the active substance in the stomach. The reference drug is "Vemlidy® 25 mg Film Tablet", which contains 25 mg of TAF in "hemifumarate" form, is under patent protection until 15.08.2032 by Gilead, and so the "monofumarate" form was used in the present study. At first, a pilot study was conducted involving 12 subjects under fed conditions. The results of the pilot study revealed the test and reference products were not bioequivalent, as a result of insufficient statistical power and high inter-subject variability. Secondly, a physiologically based pharmacokinetic (PBPK) simulation was performed based on the pilot study results and literature data. Finally, the power of the design was increased and the pivotal study design was optimized into a four-period, full-replicated, cross-over study with 34 subjects under fed conditions and it was concluded that the test and reference products were bioequivalent. In conclusion, the present study proved the importance of a correct study design with higher statistical power for a BCS Class III compound with high variability, to present the pharmacokinetics.
Assuntos
Alanina , Disponibilidade Biológica , Estudos Cross-Over , Comprimidos , Tenofovir , Equivalência Terapêutica , Tenofovir/farmacocinética , Tenofovir/administração & dosagem , Tenofovir/análogos & derivados , Humanos , Projetos Piloto , Alanina/farmacocinética , Alanina/química , Adulto , Masculino , Administração Oral , Adulto Jovem , Adenina/análogos & derivados , Adenina/farmacocinética , Adenina/administração & dosagem , Pró-Fármacos/farmacocinética , Pró-Fármacos/administração & dosagemRESUMO
INTRODUCTION: Peritoneal dialysis (PD) is an effective renal replacement modality in people with HIV (PWH) with end-stage kidney disease (ESKD), particularly those with residual kidney function. Data on pharmacokinetics (PK) of antiretrovirals in patients on peritoneal dialysis are limited. METHODS: A single-participant study was performed on a 49-year-old gentleman with ESKD on PD and controlled HIV on once daily dolutegravir (DTG) 50 mg + tenofovir alafenamide (TAF) 25 mg / emtricitabine (FTC) 200 mg. He underwent serial blood plasma, peripheral blood mononuclear cell, and urine PK measurements over 24 h after an observed DTG + FTC/TAF dose. RESULTS: Plasma trough (Cmin) concentrations of TAF, tenofovir (TFV), FTC, and DTG were 0.05, 164, 1,006, and 718 ng/mL, respectively. Intracellular trough concentrations of TFV-DP and FTC-TP were 1142 and 11,201 fmol/million cells, respectively. Compared to published mean trough concentrations in PWH with normal kidney function, observed TFV and FTC trough concentrations were 15.5- and 20-fold higher, while intracellular trough concentrations of TFV-DP and FTC-TP were 2.2-fold and 5.4-fold higher, respectively. TFV and FTC urine levels were 20 times lower than in people with normal GFR. CONCLUSIONS: In a single ESKD PWH on PD, daily TAF was associated with plasma TFV and intracellular TFV-DP trough concentrations 15-fold and 2-fold higher than those of people with uncompromised kidney function, potentially contributing to nephrotoxicity. This suggests that TFV accumulates on PD; thus, daily TAF in PD patients may require dose adjustment or regimen change to optimize treatment, minimize toxicity, and preserve residual kidney function.
Assuntos
Adenina , Alanina , Fármacos Anti-HIV , Emtricitabina , Infecções por HIV , Compostos Heterocíclicos com 3 Anéis , Falência Renal Crônica , Oxazinas , Diálise Peritoneal , Piperazinas , Piridonas , Tenofovir , Humanos , Masculino , Compostos Heterocíclicos com 3 Anéis/farmacocinética , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Oxazinas/farmacocinética , Piridonas/farmacocinética , Pessoa de Meia-Idade , Tenofovir/farmacocinética , Tenofovir/uso terapêutico , Tenofovir/análogos & derivados , Emtricitabina/farmacocinética , Emtricitabina/uso terapêutico , Piperazinas/farmacocinética , Infecções por HIV/tratamento farmacológico , Fármacos Anti-HIV/farmacocinética , Fármacos Anti-HIV/uso terapêutico , Alanina/farmacocinética , Adenina/análogos & derivados , Adenina/farmacocinética , Adenina/uso terapêutico , Falência Renal Crônica/terapiaRESUMO
BACKGROUND: On-demand topical products could be an important tool for human immunodeficiency virus (HIV) prevention. We evaluated the safety, pharmacokinetics, and ex vivo pharmacodynamics of a tenofovir alafenamide/elvitegravir (TAF/EVG, 20â mg/16â mg) insert administered rectally. METHODS: MTN-039 was a phase 1, open-label, single-arm, 2-dose study. Blood, rectal fluid, and rectal tissue were collected over 72â hours following rectal administration of 1 and 2 TAF/EVG inserts for each participant. RESULTS: TAF/EVG inserts were safe and well tolerated. EVG and tenofovir (TFV) were detected in blood plasma at low concentrations: median peak concentrations after 2 inserts were EVG 2.4â ng/mL and TFV 4.4â ng/mL. Rectal tissue EVG peaked at 2 hours (median, 2 inserts = 9â ng/mg) but declined to below limit of quantification in the majority of samples at 24 hours, whereas tenofovir diphosphate (TFV-DP) remained high >2000â fmol/million cells for 72 hours with 2 inserts. Compared to baseline, median cumulative log10 HIV p24 antigen of ex vivo rectal tissue HIV infection was reduced at each time point for both 1 and 2 inserts (P < .065 and P < .039, respectively). DISCUSSION: Rectal administration of TAF/EVG inserts achieved high rectal tissue concentrations of EVG and TFV-DP with low systemic drug exposure and demonstrable ex vivo inhibition of HIV infection for 72â hours. Clinical Trials Registration . NCT04047420.
Assuntos
Adenina , Administração Retal , Alanina , Fármacos Anti-HIV , Infecções por HIV , Quinolonas , Tenofovir , Humanos , Tenofovir/farmacocinética , Tenofovir/administração & dosagem , Tenofovir/análogos & derivados , Infecções por HIV/prevenção & controle , Infecções por HIV/tratamento farmacológico , Masculino , Quinolonas/farmacocinética , Quinolonas/administração & dosagem , Quinolonas/efeitos adversos , Adulto , Fármacos Anti-HIV/farmacocinética , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Feminino , Alanina/farmacocinética , Alanina/administração & dosagem , Pessoa de Meia-Idade , Adenina/análogos & derivados , Adenina/farmacocinética , Adenina/administração & dosagem , Adenina/efeitos adversos , Reto/virologia , Adulto Jovem , HIV-1/efeitos dos fármacos , Combinação de MedicamentosRESUMO
AIMS: Many transgender and gender diverse (TGD) individuals have expressed concerns about the potential for oral pre-exposure prophylaxis to affect hormonal concentrations achieved from taking gender-affirming hormone therapy (GAHT). The purpose of this study was to understand the bidirectional effects between hormone and intraerythrocytic tenofovir diphosphate concentrations when switching from tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) to tenofovir alafenamide/emtricitabine (TAF/FTC) in TGD users/nonusers of GAHT. METHODS: The study evaluated stored blood samples and dried blood spot cards from TGD adults without HIV who took ≥12 weeks of TDF/FTC and then switched to ≥12 weeks of TAF/FTC for pre-exposure prophylaxis. RESULTS: Thirty-nine individuals met the study inclusion criteria. Regardless of sex assigned at birth and the use of GAHT, there were no significant differences in hormone concentrations when individuals taking GAHT were taking TDF/FTC and then switched to TAF/FTC. Further, there was no significant difference in intraerythrocytic tenofovir diphosphate concentrations between users and nonusers of GAHT. CONCLUSION: There are no bidirectional effects between hormone and intraerythocytic tenofovir diphosphate concentrations when switching from TDF/FTC to TAF/FTC in TGD users/nonusers of GAHT.
Assuntos
Adenina , Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Tenofovir , Pessoas Transgênero , Humanos , Masculino , Tenofovir/administração & dosagem , Tenofovir/análogos & derivados , Adulto , Infecções por HIV/prevenção & controle , Feminino , Profilaxia Pré-Exposição/métodos , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/farmacocinética , Adenina/análogos & derivados , Adenina/administração & dosagem , Adenina/uso terapêutico , Adenina/farmacocinética , Adenina/sangue , Pessoa de Meia-Idade , Emtricitabina/administração & dosagem , Alanina/administração & dosagem , Alanina/sangue , Substituição de Medicamentos , Combinação de Medicamentos , Adulto Jovem , Organofosfatos/administração & dosagem , Organofosfatos/sangue , Combinação Emtricitabina e Fumarato de Tenofovir Desoproxila/administração & dosagem , Ácidos Fosforosos/administração & dosagemRESUMO
BACKGROUND: Coformulated bictegravir, emtricitabine, and tenofovir alafenamide is a single-tablet regimen and was efficacious and well tolerated in children and adolescents with HIV (aged 6 years to <18 years) in a 48-week phase 2/3 trial. In this study, we report data from children aged at least 2 years and weighing 14 kg to less than 25 kg. METHODS: We conducted this open-label, multicentre, multicohort, single-arm study in South Africa, Thailand, Uganda, and the USA. Participants were virologically suppressed children with HIV, aged at least 2 years, weighing 14 kg to less than 25 kg. Participants received bictegravir (30 mg), emtricitabine (120 mg), and tenofovir alafenamide (15 mg) once daily, switching to bictegravir (50 mg), emtricitabine (200 mg), and tenofovir alafenamide (25 mg) upon attaining a bodyweight of at least 25 kg. The study included pharmacokinetic evaluation at week 2 to confirm the dose of coformulated bictegravir, emtricitabine, and tenofovir alafenamide for this weight band by comparing with previous adult data. Primary outcomes were bictegravir area under the curve over the dosing interval (AUCtau) and concentration at the end of the dosing interval (Ctau) at week 2, and incidence of treatment-emergent adverse events and laboratory abnormalities until the end of week 24 in all participants who received at least one dose of bictegravir, emtricitabine, and tenofovir alafenamide. This study is registered with ClinicalTrials.gov, NCT02881320. FINDINGS: Overall, 22 participants were screened (from Nov 14, 2018, to Jan 11, 2020), completed treatment with bictegravir, emtricitabine, and tenofovir alafenamide (until week 48), and entered an extension phase. The geometric least squares mean (GLSM) ratio for AUCtau for bictegravir was 7·6% higher than adults (GLSM ratio 107·6%, 90% CI 96·7-119·7); Ctau was 34·6% lower than adults (65·4%, 49·1-87·2). Both parameters were within the target exposure range previously found in adults, children, or both". Grade 3-4 laboratory abnormalities occurred in four (18%) participants by the end week 24 and six (27%) by the end of week 48. Drug-related adverse events occurred in three participants (14%) by the end of week 24 and week 48; none were severe. No Grade 3-4 adverse events, serious adverse events, or adverse events leading to discontinuation occurred by the end of week 24 and week 48. INTERPRETATION: Data support the use of single-tablet coformulated bictegravir (30 mg), emtricitabine (120 mg), and tenofovir alafenamide (15 mg) for treatment of HIV in children aged at least 2 years and weighing 14 kg to less than 25 kg. FUNDING: Gilead Sciences.
Assuntos
Adenina , Alanina , Amidas , Fármacos Anti-HIV , Emtricitabina , Infecções por HIV , Compostos Heterocíclicos com 3 Anéis , Compostos Heterocíclicos de 4 ou mais Anéis , Piperazinas , Piridonas , Tenofovir , Tenofovir/análogos & derivados , Humanos , Emtricitabina/farmacocinética , Emtricitabina/administração & dosagem , Emtricitabina/uso terapêutico , Emtricitabina/efeitos adversos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Tenofovir/farmacocinética , Tenofovir/administração & dosagem , Tenofovir/efeitos adversos , Tenofovir/uso terapêutico , Criança , Masculino , Feminino , Fármacos Anti-HIV/farmacocinética , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Pré-Escolar , Alanina/farmacocinética , Alanina/efeitos adversos , Compostos Heterocíclicos de 4 ou mais Anéis/farmacocinética , Compostos Heterocíclicos de 4 ou mais Anéis/efeitos adversos , Compostos Heterocíclicos de 4 ou mais Anéis/administração & dosagem , Amidas/farmacocinética , Adolescente , Piridonas/farmacocinética , Piridonas/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/farmacocinética , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Piperazinas/efeitos adversos , Piperazinas/farmacocinética , Adenina/análogos & derivados , Adenina/farmacocinética , Adenina/efeitos adversos , Adenina/administração & dosagem , Adenina/uso terapêutico , Tailândia , Estados Unidos , África do Sul , Combinação de Medicamentos , Uganda , Carga Viral/efeitos dos fármacosRESUMO
BACKGROUND AND OBJECTIVE: Within the UNIVERSAL project (RIA2019PD-2882) we aim to develop a paediatric dolutegravir (DTG)/emtricitabine (FTC or F)/tenofovir alafenamide (TAF) fixed-dose combination. To inform dosing of this study, we undertook a relative bioavailability (RBA) study in healthy volunteers to investigate a potential pharmacokinetic effect when paediatric formulations of DTG and F/TAF are taken together. METHODS: Participants received all of the following treatments as paediatric formulations in randomised order: a single dose of 180/22.5 mg F/TAF; a single dose of 30 mg DTG; a single dose of 180/22.5 mg F/TAF plus 30 mg DTG. Blood concentrations of DTG, FTC, TAF, and tenofovir (TFV) were measured over 48 h post-dose. If the 90% confidence intervals (CIs) of the geometric least squares mean (GLSM) ratios of area under the curve (AUC) and maximum concentration (Cmax) of each compound were within 0.70-1.43, we considered this as no clinically relevant PK interaction. RESULTS: A total of 15 healthy volunteers were included. We did not observe a clinically relevant PK interaction between the paediatric DTG and F/TAF formulations for the compounds DTG, FTC, and TFV. For TAF, the lower boundaries of the 90% CIs of the GLSM ratios of the AUC0-∞ and Cmax fell outside our acceptance criteria of 0.70-1.43. CONCLUSIONS: Although TAF AUC and Cmax 90% CIs fell outside the pre-defined criteria (0.62-1.11 and 0.65-1.01, respectively), no consistent effect on TAF PK was observed, likely due to high inter-subject variability. Moreover, there are several reasons to rely on TFV exposure as being more clinically relevant than TAF exposure. Therefore, we found no clinically relevant interactions in this study.
Assuntos
Alanina , Disponibilidade Biológica , Emtricitabina , Voluntários Saudáveis , Compostos Heterocíclicos com 3 Anéis , Oxazinas , Piperazinas , Piridonas , Comprimidos , Tenofovir , Humanos , Piridonas/farmacocinética , Compostos Heterocíclicos com 3 Anéis/farmacocinética , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/sangue , Tenofovir/farmacocinética , Tenofovir/administração & dosagem , Tenofovir/análogos & derivados , Masculino , Emtricitabina/farmacocinética , Emtricitabina/administração & dosagem , Piperazinas/farmacocinética , Feminino , Adulto , Oxazinas/farmacocinética , Oxazinas/administração & dosagem , Alanina/farmacocinética , Alanina/administração & dosagem , Combinação de Medicamentos , Adulto Jovem , Adenina/análogos & derivados , Adenina/farmacocinética , Adenina/administração & dosagem , Adenina/sangue , Fármacos Anti-HIV/farmacocinética , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/sangue , Área Sob a Curva , Pessoa de Meia-Idade , Adolescente , Estudos Cross-OverRESUMO
PURPOSE: Adefovir (as dipivoxil) was selected as a probe drug in a previous transporter cocktail phenotyping study to assess renal organic anion transporter 1 (OAT1), with renal clearance (CLR) as the primary parameter describing renal elimination. An approximately 20% higher systemic exposure of adefovir was observed when combined with other cocktail components (metformin, sitagliptin, pitavastatin, and digoxin) compared to sole administration. The present evaluation applied a population pharmacokinetic (popPK) modeling approach to describe adefovir pharmacokinetics as a cocktail component in more detail. METHODS: Data from 24 healthy subjects were reanalyzed. After establishing a base model, covariate effects, including the impact of co-administered drugs, were assessed using forward inclusion then backward elimination. RESULTS: A one-compartment model with first-order absorption (including lag time) and a combination of nonlinear renal and linear nonrenal elimination best described the data. A significantly higher apparent bioavailability (73.6% vs. 59.0%) and a lower apparent absorption rate constant (2.29 h-1 vs. 5.18 h-1) were identified in the combined period compared to the sole administration period, while no difference was seen in renal elimination. The population estimate for the Michaelis-Menten constant (Km) of the nonlinear renal elimination was 170 nmol/L, exceeding the observed range of adefovir plasma maximum concentration, while the maximum rate (Vmax) of nonlinear renal elimination was 2.40 µmol/h at the median absolute estimated glomerular filtration rate of 105 mL/min. CONCLUSION: The popPK modeling approach indicated that the co-administration primarily affected the apparent absorption and/or prodrug conversion of adefovir dipivoxil, resulting in the minor drug-drug interaction observed for adefovir as a victim. However, renal elimination remained unaffected. The high Km value suggests that assessing renal OAT1 activity by CLR has no relevant misspecification error with the cocktail doses used.
Assuntos
Adenina , Modelos Biológicos , Organofosfonatos , Humanos , Organofosfonatos/farmacocinética , Organofosfonatos/sangue , Organofosfonatos/administração & dosagem , Adenina/análogos & derivados , Adenina/farmacocinética , Adenina/administração & dosagem , Masculino , Adulto , Feminino , Proteína 1 Transportadora de Ânions Orgânicos/metabolismo , Proteína 1 Transportadora de Ânions Orgânicos/genética , Interações Medicamentosas , Fenótipo , Pessoa de Meia-Idade , Adulto Jovem , Digoxina/farmacocinética , Digoxina/sangue , Digoxina/administração & dosagem , Metformina/farmacocinética , Metformina/administração & dosagem , Metformina/sangue , Fosfato de Sitagliptina/farmacocinética , Disponibilidade BiológicaRESUMO
OBJECTIVES: We measured the intracellular concentrations of tenofovir-diphosphate (TFV-DP) and emtricitabine-triphosphate (FTC-TP) in dried blood spots (DBS) for pre-exposure prophylaxis (PrEP) adherence using sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS). METHODS: A total of 191 DBS were obtained from 85 participants who were receiving tenofovir disoproxil fumarate (TDF; 300 mg) and emtricitabine (FTC; 200 mg) as PrEP at the Sexual Health Clinic, National Center for Global Health and Medicine, Tokyo, Japan. DBS punch (3 mm) added to 25 µL of 50% methanol and 400 µL of internal standard solution was used for solid phase extraction. Chromatographic separation was achieved on an Atlantis Premier BEH C18 AX Column (50 mm × 2.1 mm i.d.; particle size 1.7 µm) using gradient elution (flow rate: 0.6 mL/min); injection volume: 7 µL and run time: 5.5 min. Calibration curves for the two drugs were linear in the range 0.05-12.5 ng/punch. RESULTS: We determined the intracellular TFV-DP and FTC-TP concentrations in 191 DBS obtained from 85 patients administered with TDF and FTC as PrEP. The analytical performance data (calibration curve and QC samples) for all the analytical runs met the acceptance criteria. Intracellular concentrations of TFV-DP and FTC-TP in the DBS remained stable for at least 24 h after oral administration. CONCLUSIONS: A multiplex LC-MS/MS method was successfully developed for DBS, which can be useful for monitoring the levels of TFV-DP and FTC-TP in individuals receiving PrEP.
Assuntos
Fármacos Anti-HIV , Teste em Amostras de Sangue Seco , Emtricitabina , Infecções por HIV , Profilaxia Pré-Exposição , Espectrometria de Massas em Tandem , Tenofovir , Humanos , Emtricitabina/farmacocinética , Emtricitabina/administração & dosagem , Emtricitabina/sangue , Profilaxia Pré-Exposição/métodos , Infecções por HIV/prevenção & controle , Teste em Amostras de Sangue Seco/métodos , Espectrometria de Massas em Tandem/métodos , Masculino , Fármacos Anti-HIV/sangue , Fármacos Anti-HIV/farmacocinética , Fármacos Anti-HIV/administração & dosagem , Feminino , Adulto , Cromatografia Líquida/métodos , Pessoa de Meia-Idade , Tenofovir/sangue , Tenofovir/farmacocinética , Tenofovir/administração & dosagem , Adenina/análogos & derivados , Adenina/administração & dosagem , Adenina/farmacocinética , Adenina/sangue , Adenina/uso terapêutico , Adesão à Medicação , Organofosfatos/sangue , Organofosfatos/farmacocinética , Organofosfatos/administração & dosagem , Organofosfatos/análise , Polifosfatos/análise , Polifosfatos/sangueRESUMO
OBJECTIVE: We assessed the association and concordance between self-reported oral pre-exposure prophylaxis (PrEP) intake in a diary app and intraerythrocytic drug metabolite concentrations. DESIGN: AMPrEP was a prospective demonstration study providing daily and event-driven PrEP to MSM in Amsterdam, the Netherlands (2015-2020). METHODS: Participants could record their PrEP intake in a diary app. Dried blood spots (DBS) were taken at 6, 12, 24, and 48âmonths and analysed for tenofovir diphosphate (TFV-DP) and emtricitabine triphosphate (FTC-TP) concentrations. We included TFV-DP measurements preceded by diary completion on at least 90% of days in the 6âweeks prior. We examined the association between self-reported PrEP intake (i.e. number of pills) and TFV-DP concentrations using tobit regression with a random intercept per participant. We also calculated concordance between categorized PrEP intake (i.e. <2, 2-3, 4-6 or 7 pills per week) and categorized TFV-DP concentrations (i.e. <350, 350-699,700-1249 or ≥1250âfmol/punch) using weighted Cohen's kappa. Last, we calculated concordance between self-reported recent PrEP intake (yes/no, in past 2 days) and quantifiability of FTC-TP (yes/no) using Cohen's kappa. RESULTS: Seven hundred and fifty-nine DBS measurements from 282 MSM were included. Self-reported PrEP intake was strongly and positively associated with TFV-DP concentration ( ß â=â0.77, 95% CIâ=â0.70-0.84, P â<â0.0001). Concordance between categorized PrEP intake and TFV-DP concentration was moderate ( κ â=â0.44, 95% CIâ=â0.39-0.50). Concordance between self-reported recent PrEP intake and FTC-TP quantifiability was perfect ( κ â=â0.83, 95% CI 0.76-0.90). CONCLUSION: Self-reported PrEP intake in a diary app is strongly correlated with actual use, and therefore reliable for comparing PrEP adherence between groups. Still, suboptimal criterion validity according to clinically relevant categories warrants caution when assessing 6-week reported adherence for individuals.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Humanos , Profilaxia Pré-Exposição/métodos , Masculino , Países Baixos , Infecções por HIV/prevenção & controle , Estudos Prospectivos , Adulto , Fármacos Anti-HIV/administração & dosagem , Organofosfatos/administração & dosagem , Adenina/análogos & derivados , Adenina/administração & dosagem , Adenina/farmacocinética , Homossexualidade Masculina , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Autorrelato , Tenofovir/administração & dosagem , Teste em Amostras de Sangue SecoRESUMO
BACKGROUND AND OBJECTIVE: The life expectancy of people living with HIV (PLWHIV) has significantly improved in recent decades, mostly due to antiretroviral (ARV) therapy. Aging can affect the pharmacokinetics of drugs and, as a consequence, increase the risk of drug interactions and toxicity that may impact treatment. The aim of this study was to carry out a systematic review of the literature on the effect of aging on ARV pharmacokinetics. METHODS: Searches were performed in the BVS, EMBASE and PUBMED databases until November 2022. All studies available in English, Spanish and Portuguese investigating the pharmacokinetics of ARV approved by the US Food and Drug Administration (FDA) from 2005 to 2020 were selected. Peer-reviewed publications were included if they met all criteria: adults (≥ 18 years of age) living with or without HIV; report any pharmacokinetic parameter or plasma concentration of at least one of the following ARVs: tenofovir alafenamide fumarate (TAF); doravirine (DOR), rilpivirine (RIL) and etravirine (ETR); darunavir (DRV), tipranavir (TPV) and fostemsavir (FTR); dolutegravir (DTG), raltegravir (RAL), bictegravir (BIC) and elvitegravir (EVG); maraviroc (MVC); ibalizumab (IBA); cobicistat (COBI). Pharmacokinetic parameters were reported stratified per age group: young adults (aged 18-49 years) or older (age ≥ 50 years) and all studies were evaluated for quality. The review protocol was registered in the PROSPERO database (registration number CRD42021236432). RESULTS: Among 97 studies included, 20 reported pharmacokinetic evaluation in older individuals (age ≥ 50 years). Twenty five percent of the articles were phase I randomized clinical trials with HIV-negative participants and non-compartmental pharmacokinetic analysis presenting the parameters area under the curve (AUC) and peak drug concentration (Cmax). Seven age-stratified studies evaluated BIC, ETR, DRV, DTG, DOR and RAL. We found publications with discordant results for ETR and DTG pharmacokinetics in different age groups. DRV exposure was highly variable but modestly increased in aging PLWHIV. In contrast, no influence of age on BIC, DOR and RAL exposure was observed. A variability in pharmacokinetic parameters could be observed for the other ARVs (TAF and MVC) in different age groups. CONCLUSION: Exposure to DRV increases modestly with age, while exposure to BIC, DOR and RAL appears to be unaffected by age. As the available evidence to confirm a potential effect of aging on ARV pharmacokinetics is limited, further studies are necessary.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Adulto Jovem , Humanos , Idoso , Adolescente , Fármacos Anti-HIV/farmacocinética , Tenofovir/uso terapêutico , Preparações Farmacêuticas , Antirretrovirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Raltegravir Potássico/uso terapêutico , Adenina/farmacocinética , Darunavir/uso terapêuticoRESUMO
BACKGROUND: Crushing or dissolving bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) tablets is not recommended because there are no data supporting this practice. METHODS: A crossover, randomized trial in healthy adults (NCT04244448) investigated the bioavailability of two off-label uses of BIC/TAF/FTC (50/200/25â mg), dissolved in water or crushed in apple compote, compared with the solid tablet. Pharmacokinetic (PK) parameters were estimated from sequential intensive plasma antiretroviral concentrations over a 72â h period post dose. Bioequivalence was met if the 90% CIs of the geometric least-squares means ratios comparing BIC/TAF/FTC exposures (AUC and Cmax) from the experimental phases were within 80%-125% of the reference. RESULTS: Eighteen subjects participated in each of the three phases. Dissolved tablet Cmax geometric mean ratio (90% CI) for BIC/TAF/FTC was 105% (93-119)/97% (87-108)/96% (74-124), respectively. Dissolved tablet AUC geometric mean ratio (90% CI) for BIC/TAF/FTC was 111% (100-122)/100% (94 to 105)/99% (81 to 120), respectively. Crushed tablet Cmax geometric mean ratio (90%) CI for BIC/TAF/FTC was 110% (97 to 124)/70% (63-78)/66% (51-85), respectively. Crushed tablet AUC geometric mean ratio (90%) CI for BIC/TAF/FTC was 107% (96-118)/86% (82-91)/84% (69-103), respectively. CONCLUSIONS: Crushing BIC/TAF/FTC tablets may lead to suboptimal emtricitabine and tenofovir alafenamide drug exposures. Dissolving BIC/TAF/FTC in water may be acceptable if the tablet cannot be swallowed whole.
Assuntos
Fármacos Anti-HIV , Infecções por HIV , Humanos , Adulto , Emtricitabina/uso terapêutico , Tenofovir/uso terapêutico , Infecções por HIV/tratamento farmacológico , Disponibilidade Biológica , Estudos Cross-Over , Adenina/farmacocinética , Comprimidos , Fármacos Anti-HIV/uso terapêutico , Alanina/uso terapêuticoRESUMO
BACKGROUND: Obesity is increasing worldwide including in people living with HIV (PLWH). Antiretroviral pharmacokinetic data in obesity are limited. OBJECTIVES: To measure antiretroviral drug concentrations in obese and nonobese PLWH treated with the fixed-dose combination of efavirenz-tenofovir-emtricitabine. To determine pharmacokinetic differences across indicators of obesity and their associated immunovirological outcomes. METHODS: We conducted a cross-sectional sample analysis of 2 cohort studies. We measured mid-dose efavirenz, 8-hydroxy-efavirenz, tenofovir, and emtricitabine concentrations. Antiretroviral drug concentrations were analyzed by body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR). RESULTS: We performed a study of 213 participants: General obesity was detected in 20.4% using BMI and abdominal obesity in 53.6% using WC and 62.4% using WHR, respectively. The median concentrations of all antiretroviral drugs were lower among obese participants determined by BMI and WC, with efavirenz showing greater differences than tenofovir or emtricitabine. For BMI, results were most striking for efavirenz (1752.3 vs 2342.9 ng/mL, P = 0.002) with lower concentrations in obese participants. Using WC, efavirenz (1845.8 vs 2571.2 ng/mL, P < 0.001), tenofovir (65.8 vs 73.2 ng/mL, P = 0.036), and emtricitabine (159.5 vs 221.0 ng/mL, P = 0.005) concentrations were lower in obese participants. Eight-hydroxyefavirenz concentrations were similar in nonobese and obese participants for WC. Using WHR, the concentrations of all antiretroviral drugs were lower in the obese population, most strikingly for emtricitabine (173.5 vs 229.0 ng/mL, P = 0.015). There were no immunovirological associations. CONCLUSION: We found lower antiretroviral concentrations in all obese groups, most strikingly in participants with abdominal obesity determined by WC. Lower drug concentrations had no immunovirological associations.