Toxicity, efficacy, plasma drug concentrations and protease mutations in patients with advanced HIV infection treated with ritonavir plus saquinavir

Lorenzi, Patrizio; Yerly, Sabine; Abderrakim, K; Fathi, Marc; Rutschmann, Olivier Thierry; Overbeck, Jan von; Leduc, Dominique; Perrin, Luc; Hirschel, Bernard

doi:10.1097/00002030-199712000-00002

Cited by 97 publications

(59 citation statements)

References 11 publications

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“…Low drug levels have been associated with self-reported non-adherence (72;73) and virologic failure (74)(75)(76)(77), but not all studies have shown a benefit to measuring serum drug levels. In one study an abnormally low drug level had a specificity of 88% for detecting adherence of 90% or less (75), but another study found that the addition of drug levels to a composite adherence measure did not improve the composite measure's ability to predict viral load (78).…”

Section: Therapeutic Drug Monitoringmentioning

confidence: 99%

Practical and Conceptual Challenges in Measuring Antiretroviral Adherence

Berg

Arnsten

2006

JAIDS Journal of Acquired Immune Deficiency Syndromes

262

264

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Accurate measurement of antiretroviral adherence is essential for targeting and rigorously evaluating interventions to improve adherence and prevent viral resistance. Across diseases, medication adherence is an individual, complex, and dynamic human behavior that presents unique measurement challenges. Measurement of medication adherence is further complicated by the diversity of available measures, which have different utility in clinical and research settings. Limited understanding of how to optimize existing adherence measures has hindered progress in adherence research in both HIV and other diseases. Though self-report is the most widely used adherence measure and the most promising for use in clinical care and resource limited settings, adherence researchers have yet to develop evidence-based standards for self-reported adherence. In addition, the use of objective measures, such as electronic drug monitoring or pill counts, is limited by poor understanding of the source and magnitude of error biasing these measures. To address these limitations, research is needed to evaluate methods of combining information from different measures. The goals of this review are to describe the state of the science of adherence measurement, to discuss the advantages and disadvantages of common adherence measurement methods, and to recommend directions for improving antiretroviral adherence measurement in research and clinical care.

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Section: Therapeutic Drug Monitoringmentioning

confidence: 99%

Practical and Conceptual Challenges in Measuring Antiretroviral Adherence

Berg

Arnsten

2006

JAIDS Journal of Acquired Immune Deficiency Syndromes

262

264

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“…Los beneficios de la terapia antiviral pueden verse comprometidos cuando aparecen ciertos factores, como defectos de la inmunidad del huésped, alta capacidad del virus para desarrollar resistencia a los fármacos (13,(17)(18)(19)(20)(21), y pobre cumplimiento del tratamiento. A esto se suma el alto costo y el bajo acceso a los medicamentos en los países en vía de desarrollo, así como la alta toxicidad de los mismos (22,23). La estrategia del manejo actual es el uso de terapia antirretroviral altamente activa (highly active antiretroviral treatment, HAART) (24,25).…”

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Patrones de prescripción de antirretrovirales en 997 pacientes colombianos

Machado

Alzate

2008

biomedica

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Introducción. El tratamiento antirretroviral de la infección por virus de inmunodeficiencia humana ha mejorado la supervivencia y la calidad de vida de los pacientes desde el advenimiento de la terapia combinada en 1996. Objetivos. Conocer el manejo farmacológico de la infección por VIH/sida. Materiales y métodos. Estudio descriptivo observacional con selección de pacientes con infección por VIH/sida, de ambos sexos, de todas las edades, en tratamiento, al menos, durante tres meses (julio a septiembre de 2006) localizados en diferentes ciudades colombianas y afiliados al Sistema General de Seguridad Social en Salud. Se diseñó una base de datos con registros sobre el consumo de medicamentos antirretrovirales, recolectados por la empresa que dispensa dichos fármacos a los pacientes de las entidades promotoras de salud. Resultados. Se estudiaron 997 pacientes con edad promedio de 37,7±13,2 años, 82,6% de hombres. Todos los pacientes recibían terapia con tres o más antirretrovirales; el orden de prescripción de medicamentos fue: inhibidores de nucleósidos de transcriptasa inversa (96,4%), inhibidores de transcriptasa inversa no nucleósidos (54,9%), inhibidores de proteasa (39,8%) y otros (0,4%), todos a dosis adecuadas. Las combinaciones más empleadas fueron: lamivudina-zidovudina-efavirenz (35%), lamivudina-zidovudina con lopinavir/ritonavir (8,4%), abacavir con lamivudina-zidovudina (5,5%), lamivudina-zidovudina con nevirapina (5,2 %) y otras 65 asociaciones diferentes (45,9%). Conclusiones. Todos los antirretrovirales se están utilizando a las dosis establecidas internacionalmente y predominan patrones de prescripción racionales para iniciar la terapia. Sin embargo, el encontrar 69 asociaciones diferentes de antirretrovirales lleva a considerar que no hay adecuados criterios para la implementación de los esquemas después del inicio del tratamiento, guiados según los datos científicos y quienes los prescriben adoptan múltiples opciones por fuera de lo recomendado a nivel mundial.Palabras clave: síndrome de inmunodeficiencia adquirida/terapia, terapia antirretroviral altamente activa, prescripción de medicamentos, Colombia. Patterns of antiretroviral drug prescripcion in 997 Colombian patientsIntroduction. Antiretroviral therapy for treatment of human immunodeficiency virus type 1 (HIV-1) infection has improved steadily since the advent of combination therapy in 1996. Objective. The pharmacological therapies of the infection by HIV/AIDS were documented in order to determine if effective treatment regimes were prescribed. Materials and methods. Pharmacological therapies of the human immunodeficiency virus infection were compared in 997 patients affiliated with the health security system, of both sexes and all ages. All had been in treatment for more than three months (July-September 2006) and were distributed in 15 Colombian cities. The data were retrieved from medication consumption files which were maintained by the institutions that had distributed medications to the selected patients. Results. The average age of...

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“…While previous studies have shown the cross-sectional association of the virologic response with a higher C trough (1,5,6,9,15), the discrimination of C trough , C max , and AUC as pharmacodynamic predictors for PI activity is generally not feasible due to the correlation between these parameters. This is the first longitudinal study to demonstrate that the C trough is associated with the in vivo antiviral activities of PIs, independent of C max and AUC.…”

Section: Discussionmentioning

confidence: 95%

“…C trough s of PIs have been associated with virologic suppression in several clinical studies (1,5,6,9,15), as have AUCs in other studies (1,14). Enhancement of indinavir C trough s by the addition of ritonavir to the antiretroviral drug regimen could theoretically enhance virologic suppression.…”

mentioning

confidence: 96%

“…Suboptimal drug exposure in patients receiving combination antiretroviral therapy has been increasingly recognized as an important contributor to virologic failure, particularly with drugs in the protease inhibitor (PI) class (1,2,5,6,15,19). Subinhibitory concentrations of drugs may be a consequence of poor adherence to the drug regimen, but they may also occur due to the wide variabilities in metabolism and the levels in plasma seen with many of the PIs.…”

mentioning

confidence: 99%

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Virtual Inhibitory Quotient Predicts Response to Ritonavir Boosting of Indinavir-Based Therapy in Human Immunodeficiency Virus-Infected Patients With Ongoing Viremia

&NA;

2002

Infectious Diseases in Clinical Practice

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Depending on the degree of underlying resistance present, optimization of the pharmacokinetics of protease inhibitors may result in improved virologic suppression. Thirty-seven human immunodeficiency virus (HIV)-infected subjects who had chronic detectable viremia and who were receiving 800 mg of indinavir three times a day (TID) were switched to 400 mg of indinavir BID with 400 mg of ritonavir two times a day (BID) for 48 weeks. Full pharmacokinetic evaluations were obtained for 12 subjects before the switch and 3 weeks after the switch. Combination therapy increased the indinavir predose concentrations in plasma by 6.47-fold, increased the minimum concentration in serum by 3.41-fold, and reduced the maximum concentration in serum by 57% without significantly changing the area under the plasma concentration-time curve at 24 h. At week 3, 58% (21 of 36) of the subjects for whom postbaseline measurements were available achieved a viral load in plasma of <50 copies/ml or a reduction from the baseline load of >0.5 log 10 copies/ml. Of these subjects, 82% (14 of 17) whose viruses had three or fewer protease inhibitor mutations and 88% (14 of 16) whose viruses had an indinavir virtual phenotypic susceptibility test of more than sixfold less than that for the baseline isolate were considered virologic responders. The indinavir virtual inhibitory quotient, which is a function of baseline indinavir phenotypic resistance (estimated by virtual phenotype) and the indinavir predose concentration in plasma achieved with indinavir-ritonavir combination therapy, was the best predictor of a viral load reduction. Sixteen subjects discontinued the study by week 48 due to adverse events, predominantly related to hyperlipidemia. Pharmacokinetic intensification of indinavir-based therapy with ritonavir reduced the viral loads in subjects but added toxicity. The virtual inhibitory quotient, which incorporates both baseline viral resistance and the level of drug exposure in plasma, was superior to either baseline resistance or drug exposure alone in predicting the virologic response.

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Toxicity, efficacy, plasma drug concentrations and protease mutations in patients with advanced HIV infection treated with ritonavir plus saquinavir

Cited by 97 publications

References 11 publications

Practical and Conceptual Challenges in Measuring Antiretroviral Adherence

Practical and Conceptual Challenges in Measuring Antiretroviral Adherence

Patrones de prescripción de antirretrovirales en 997 pacientes colombianos

Virtual Inhibitory Quotient Predicts Response to Ritonavir Boosting of Indinavir-Based Therapy in Human Immunodeficiency Virus-Infected Patients With Ongoing Viremia

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