Plasma and Intracellular Antiretroviral Concentrations in HIV-Infected Patients under Short Cycles of Antiretroviral Therapy

Zehnacker, Laura; Abé, Emuri; Mathez, Dominique; Alvarez, Jean‐Claude; Leibowitch, Jacques; Azoulay, Stéphane

doi:10.1155/2014/724958

Cited by 3 publications

(2 citation statements)

References 18 publications

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“…The plasma concentration therefore cannot reflect the target intracellular concentration, especially for PI, whose concentrations were not measurable in blood. We previously demonstrated 28 that ATV and LPV are still measurable in peripheral blood mononuclear cells (PBMCs) 85‐100 hours after intake, which corresponds approximately to the OFF period delay, despite undetectable plasma concentration. Nagano et al 29 showed that the intracellular elimination half‐life of DRV was longer than the plasma half‐life (47.6 h).…”

Section: Discussionmentioning

confidence: 99%

Pharmacological data of a successful 4‐days‐a‐week regimen in HIV antiretroviral therapy (ANRS 162‐4D trial)

Abé

Assoumou

Truchis

et al. 2020

Brit J Clinical Pharma

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Few data are available on plasma concentrations of antiretroviral therapy (ARV) during intermittent treatment. Objective: To compare plasma concentrations in OFF vs ON treatment periods at several time points during treatment. Methods: During a successful 48-week multicenter study (ANRS 162-4D trial) of 4 days with treatment (ON) followed by 3 days without treatment (OFF) in adults treated by two nucleoside analogues and a third agent belonging to a boosted protease-inhibitor (PI, darunavir [DRV], atazanavir [ATV], lopinavir [LPV]) or a non-nucleoside-reverse-transcriptase inhibitor (NNRTI, efavirenz [EFV], etravirine [ETR], rilpivirine [RPV]) conducted in 100 patients (96% success), we determined the plasma concentrations of ARV. Blood samples were collected for analysis at inclusion (W0, 7/7 strategy for all patients), W16 and W40 (ON) and at W4, W8, W12, W24, W32 and W48 (OFF). Results: A total of 866 samples was analysed. Plasma concentrations were not statistically lower after 4 days (ON) vs 7/7 days of treatment except for RPV (−30 ng/mL at 4/7, P = 0.003). Significant lower plasma concentrations were observed for OFF vs ON except for ETR (n = 5, P = 0.062). Overall, 87.1% of ON concentrations (ATV 92.1%, DRV 51.1%, LPV 62.5%, EFV 94.4%, ETR 100% and RPV 94.9%) and 21.8% of OFF concentrations (ATV 1.4%, DRV 0.0%, LPV 0.0%, EFV 16.0%, ETR 92.6% and RPV 39.0%) were above the theoretical limit of efficacy of the molecule. In the OFF period, 85.8% of PI concentrations were under the limit of quantification, while 98.0% of NNRTI concentrations were quantifiable. Conclusion: Despite low/undetectable PI/NNRTI plasma concentrations in the OFF period, patients maintained an undetectable viral load. The mechanistic explanation should be investigated.

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Section: Discussionmentioning

confidence: 99%

Pharmacological data of a successful 4‐days‐a‐week regimen in HIV antiretroviral therapy (ANRS 162‐4D trial)

Abé

Assoumou

Truchis

et al. 2020

Brit J Clinical Pharma

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“…Still, since over the last 4 years 1 inadvertent viral failure per year occurred under that combination, we urged the relevant patients to set back their weekly drug intake from 2 days to no less than 3 days per week until markers predictive of failure or success on hyperintermittent combinations and regimens come to the clinic. Pharmacological quantitation of residual antiviral drugs within mononucleated cells of patients under intermittent treatment might eventually help at resolving such an issue (51).…”

Section: Treatment Outcomes Following Viral Escapesmentioning

confidence: 99%

Four days a week or less on appropriate anti‐HIV drug combinations provided long‐term optimal maintenance in 94 patients: the ICCARRE project

et al. 2015

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Short, intraweekly cycles of anti‐HIV combinations have provided intermittent, effective therapy (on 48 patients) (1). The concept is now extended to 94 patients on treatment, 4 days per week or less, over a median of 2.7 discontinuous treatment years per patient. On suppressive combinations, 94 patients volunteered to treatment, 5 and 4 days per week, or reduced stepwise to 4,3,2, and 1 days per week in 94, 84, 66, and 12 patients, respectively, on various triple, standard, antiviral combinations, or nonregistered, quadruple, antiviral combinations. Ninety‐four patients on treatment 4 days per week aggregated 165 intermittent treatment years; no viral breakthrough was observed over 87 average treatment weeks per patient, 63 of 94 having passed 2.5 intermittent treatment years on any of the antiviral combinations prescribed. On the hyperintermittent treatment of 3, 2, and 1 days per week, HIV RNA surged >50 copies, 4 weeks apart, in 18 instances (6.8 viral escapes/100 hyperdiscontinuous maintenance years). Viral escapes could have been a result of erratic adherence (EA) to regimen or follow‐up (3 patients)—drug taken at half of the daily recommended dosage (8 patients) and/or overlooked archival‐resistant HIVs from antecedent treatment failures (6 patients). Aside from the above circumstances, HIV unexpectedly rebounded in 3 patients on 2 days per week treatment and 1 patient on 1 day per week treatment, posting 2.2 intrinsic viral escapes/100 highly discontinuous treatment years. All 18 escapes were eventually reversed by 7 days per week salvage combinations, and 11 of 18 patients have been back for a second course of intermittent therapy, 4 days per week or less. Both cell‐activation markers on the surface of T lymphocytes and cell‐bound HIV DNA levels remained stable or declined. CD4/CD8 ratios rose to ≤1 in 35% of patients, whereas CD4 counts went ≤500/μl in 75%. These values were previously 7 and 40%, respectively, on 7 days per week therapy. In our aging, long, HIV‐enduring, multitreated patient cohort, treatment 4 days per week and less over 421 intermittent treatment years reduced prescription medicines by 60%—equivalent to 3 drug‐free/3 virus‐free remission year per patient—actually sparing €3 million on just 94 patients at the cost of 2.2 intrinsic viral failure/100 hyperintermittent treatment years. At no risk of viral escape, maintenance therapy, 4 days per week, would quasiuniversally offer 40% cuts off of current overprescriptions.—Leibowitch, J., Mathez, D., de Truchis, P., Ledu, D., Melchior, J. C., Carcelain, G., Izopet, J., Perronne, C., David, J. R. Four days a week or less on appropriate anti‐HIV drug combinations provided long‐term optimal maintenance in 94 patients: the ICCARRE project. FASEB J. 29, 2223‐2234 (2015). http://www.fasebj.org

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Estratégias e barreiras na aderência a terapia antirretroviral

Boas¹,

Almeida²,

Loures³

et al. 2019

HU Rev

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O principal objetivo do monitoramento de adesão a terapia antirretroviral (TARV) é manter os portadores do Vírus da Imunodefi ciência Humana (HIV) com carga viral indetectável. A adesão do paciente à TARV é um processo dinâmico, multifatorial que requer decisões compartilhadas e corresponsabilizadas entre ousuário do serviço, a equipe de saúde e a rede social de apoio, visando atender às singularidades socioculturais, melhorando a qualidade de vida dos pacientes com HIV. Existem vários nos métodos de avaliação da aderência disponíveis, com diferentes implicações para as práticas clínicas e de pesquisa, porém não está defi nido um método padrão-ouro. Tendo em vista que a efetividade da terapia depende diretamente do engajamento dos pacientes, o estudo visa expor, mediante revisão de literatura, as principais barreiras encontradas nesse contexto e as diversas estratégias utilizadas na prática clínica para promover a adesão integral dos indivíduos portadores de HIV ao tratamento.

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Plasma and Intracellular Antiretroviral Concentrations in HIV-Infected Patients under Short Cycles of Antiretroviral Therapy

Cited by 3 publications

References 18 publications

Pharmacological data of a successful 4‐days‐a‐week regimen in HIV antiretroviral therapy (ANRS 162‐4D trial)

Pharmacological data of a successful 4‐days‐a‐week regimen in HIV antiretroviral therapy (ANRS 162‐4D trial)

Four days a week or less on appropriate anti‐HIV drug combinations provided long‐term optimal maintenance in 94 patients: the ICCARRE project

Estratégias e barreiras na aderência a terapia antirretroviral

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