Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The objective of this study was to evaluate plasma concentrations of nonnucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) within several dosing schemes in a cohort of HIV-infected patients in routine clinical practice and to find possible explanations for subtherapeutic plasma concentrations. Patients were included if a PI or NNRTI was part of their antiretroviral regimen, at least one plasma concentration was obtained, and a complete medication overview from community pharmacy records was available. The study period was from January 1998 to September 2001. Each plasma concentration was related to median plasma concentrations of a pharmacokinetic reference curve, yielding a concentration ratio (CR). A cutoff CR was defined for each antiretroviral drug per specific regimen, discriminating between >or=therapeutic and subtherapeutic concentrations. For the patients with subtherapeutic concentrations, it was sorted out whether drug interactions, adverse events and self-reported symptoms, or nonadherence could be the cause of the lower than expected plasma concentration. Ninety-seven HIV-infected patients fulfilled the criteria. During the defined period, 1145 plasma concentrations were available (median, 11; interquartile range, 8-14). Three hundred fourteen (27.4%) plasma concentrations were classified subtherapeutic. Drug interactions (2; 0.6%), adverse events and self-reported symptoms (67; 21.3%), and nonadherence (14; 4.5%) could only partly explain the subtherapeutic drug levels. Consequently, a large number of the subtherapeutic plasma concentrations (73.6%) remained inexplicable. A high number of subtherapeutic plasma concentrations were observed. No clear causes were found; thus, corrective measures will be difficult to employ. Therefore, therapeutic drug monitoring (TDM) must maintain its crucial place in routine clinical care to be able to identify patients who need extra attention so that therapeutic plasma concentrations are achieved.
Ther Drug Monit 2003 Jun
PMID:Subtherapeutic antiretroviral plasma concentrations in routine clinical outpatient HIV care. 1276 66

A reversed-phase high-performance liquid chromatography method for the simultaneous quantitative determination of the currently available HIV protease inhibitors amprenavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir, the active nelfinavir metabolite M8, and the nonnucleoside reverse transcriptase inhibitor nevirapine in human plasma is described. The method involved liquid-liquid extraction from plasma, followed by high-performance liquid chromatography with an OmniSpher 5 C18 column and ultraviolet detection set at a wavelength of 215 nm for the protease inhibitors and 280 nm for nevirapine. The runtime was 25 minutes. The assay has been validated over the concentration range of 0.05 to 30 mg/L for indinavir, nelfinavir, ritonavir, and saquinavir, 0.07 to 30 mg/L for amprenavir and lopinavir, and 0.05 to 15 mg/L for M8 and nevirapine. This method proved to be simple, accurate, and precise and is useful for the therapeutic drug monitoring of protease inhibitors and the nonnucleoside reverse transcriptase inhibitor nevirapine on a routine basis.
Ther Drug Monit 2003 Jun
PMID:Simultaneous determination of the HIV drugs indinavir, amprenavir, saquinavir, ritonavir, lopinavir, nelfinavir, the nelfinavir hydroxymetabolite M8, and nevirapine in human plasma by reversed-phase high-performance liquid chromatography. 1276 71

Therapeutic drug monitoring (TDM) is becoming more widespread to optimize the treatment of patients with HIV/AIDS. The analytic component of TDM requires a drug assay with high specificity, small sample volume requirements, reasonable cost, and rapid turnaround time. This study modified a procedure for the concurrent measurement of 15 antiretrovirals by tandem mass spectrometry. The upper limit of the calibration curves was extended to 10,000 ng/mL, and the matrix for standards was changed from methanol to serum. Also, an additional drug, tenofovir, a nucleotide reverse transcription inhibitor, was included in the revised/improved method. Calibration curves showed good linearity between a concentration range of 100 and 10,000 ng/mL (r > 0.997 for all drugs). Accuracy was assessed by correlation of the calibrators with proficiency testing samples spiked with known drug concentrations and yielded results within 8% of the target values.
Ther Drug Monit 2003 Oct
PMID:Improved method for concurrent quantification of antiretrovirals by liquid chromatography-tandem mass spectrometry. 1450 75

Our considerations were prompted by observation of patients who underwent surgery due to cerebral aneurysm rupture. Elevated anti-HIV antibody titers were detected in such patients. The above condition was not observed either in subjects with intracranial hemorrhages from cerebral angiomas. The observed titers remained certainly below the cut off level indicating contact with HIV. We analyzed the subpopulations of peripheral blood lymphocytes both in the surgery patients and in the control group represented by blood collected from blood donors. On the other hand, the proliferation potential of circulating lymphocytes in the blood of patients with subarachnoid hemorrhages due to cranial aneurysm ruptures was found to be decreased. Dislocation of transposons, so-called 'unauthorized recombination' is known to occur within the framework of genetic code pathology. Endogenous human viruses have been described, and they may be involved in the development of autoimmune disorders. Additionally, viruses involved in autoimmune processes, which may be 'identical' with retrotransposons, have been described. Moreover, there are studies demonstrating that AIDS is caused by retrotransposition of genetic code material fragments. Our considerations are substantiated by ultrastructural analyses of material coming from the gyrus rectus cortex fragments, resected in patients who underwent clipping of a ruptured aneurysm of the anterior communicating artery. We demonstrated in neuronal chromatin the presence of a molecule ca. 80 nm in diameter, corresponding with its size to retroviruses or genetic material molecules with altered substructure. The authors suggest a new mechanism of development of neurological deficits in patients with ruptured cerebral aneurysms.
Med Sci Monit 2003 Oct
PMID:Can genetic material retrotransposition be a cause of pathology accompanying cerebral aneurysm rupture? 1452 41

An HIV-infected male patient experienced photophobia after a change in dosing regimen that resulted in substantially higher indinavir plasma levels as compared with a reference population. High indinavir levels were suspected to be the cause of photophobia in this patient.
Ther Drug Monit 2003 Dec
PMID:Photophobia in a patient with high indinavir plasma concentrations. 1463 61

Efavirenz is a drug subject to extensive metabolism, mainly by the cytochrome P-450 isoenzyme CYP2B6, known to exhibit extensive interindividual variability. The aim of the present study was 2-fold: to investigate the relationship between plasma concentration and clinical effects of efavirenz and to investigate the extent of the inter- and intraindividual variability of the plasma concentration measurements. From an open clinic, 68 HIV-positive patients on efavirenz-containing treatment were recruited. From each patient 1 to 5 samples were collected; 43 had more than 1 sample taken. Most samples were taken 10-24 hours after the latest dose. Efavirenz was analyzed by high-performance liquid chromatography with UV detection. The data were analyzed by the variance component model analysis of variance. Efavirenz concentrations were reproducible, and intraindividual variability constituted only 16% of the total variance. Thus, 84% of the variance was attributed to interindividual variability. The incidence of primary treatment failure was related to low plasma concentrations with a geometric mean concentration of 6.1 micromol/L compared with 8.7 micromol/L in those responding to therapy (P < 0.05). If a cutoff of 7 micromol/L is used, 10 of 13 failing to respond were below this level compared with 15 of 45 in those responding. It is concluded that efavirenz plasma concentration measurement gives reproducible results predictive of primary treatment failure. A lower bound for the therapeutic level of 7 micromol/L is proposed, and data from other authors suggests that an upper level of 13 micromol/L may be applied.
Ther Drug Monit 2004 Jun
PMID:Efavirenz plasma concentrations in HIV-infected patients: inter- and intraindividual variability and clinical effects. 1516 26

This paper provides a brief overview of therapeutic drug monitoring (TDM) in patients with HIV infection. The manuscipt not only focuses on an update on TDM in HIV infection but also provides the latest information on tandem mass spectrometric methods for antiretroviral drug quantification. Also discussed are the preliminary new and original data on free antiretroviral drug measurement in both plasma and saliva.
Ther Drug Monit 2004 Apr
PMID:Therapeutic drug monitoring for patients with HIV infection: Children's National Medical Center, Washington DC experience. 1522 48

Combined antiretroviral therapy can reduce the transmission of human immunodeficiency virus (HIV) to an unborn child to less than two percent. An HIV-infected woman of childbearing age and her medical provider are in the unique position of making treatment decisions that not only will impact the woman's health but also that of her child. Treatment recommendations for pregnant women infected with HIV state that therapies of known benefit to women should not be withheld during pregnancy, unless there are known adverse effects for the mother and fetus, and these adverse effects outweigh the benefit for the women. However, the recommendations of antiretroviral drugs for the treatment of HIV-infected pregnant women are subject to unique considerations, including potential changes in dosing requirement resulting from physiologic changes associated with pregnancy, and potential adverse effects on the development of the fetus and/or newborn. Currently there is a general lack of pharmacokinetic data in pregnant HIV-infected women. The limited available information suggests that pregnant women may be exposed to subtherapeutic drug levels of certain antiretroviral agents during the later stages of pregnancy, which can lead to the failure of virologic suppression, development of resistance and increased risk of vertical transmission of HIV infection. The available pharmacokinetic data regarding the use of antiretroviral therapy in pregnancy is reviewed.
Ther Drug Monit 2004 Apr
PMID:Safety and pharmacokinetics of antiretroviral therapy during pregnancy. 1522 49

Infection with drug-resistant HIV-1 may result from the acquisition of mutant strains or from their selection within the individual; either can compromise the efficacy of antiretroviral therapy (ART). Drug-resistance testing is recommended to assist in the choice of ART. Herein, factors that contribute to the selection of drug-resistant virus and details important to the interpretation of the genotypic and phenotypic susceptibility test results are reviewed.
Ther Drug Monit 2004 Apr
PMID:Understanding HIV-1 drug resistance. 1522 50

In this paper we present an overview on the use of TDM in the treatment of HIV-1-infected children. The processes of growth and development have a significant impact on drug metabolism. The use of TDM makes it possible to optimize plasma drug concentrations of antiretroviral drugs. This is important when one considers that the levels of viral suppression and drug toxicity in adults and children are associated with the plasma concentration of PIs and NNRTIs. Indeed, in clinical practice the use of TDM in the treatment of HIV-1-infected children has favorable results. However, there is a serious shortage of population reference values of antiretroviral medication in children. Targeting plasma drug levels in children to adult reference values may be insufficient because of the unique features of HIV infection in children. Apart from its primary function for dose optimization, TDM can also be used as a tool to assess adherence to antiviral medication. One should, however, be cautious to base assumptions on plasma levels alone because aberrant plasma levels may also be the result of other factors such as changes in nutritional habits, drug-drug interactions, or changing gastric motility. We conclude that TDM is a useful tool in the treatment of HIV-1-infected children. Additional data are needed to establish child-specific reference values and to assess the optimal method of TDM.
Ther Drug Monit 2004 Apr
PMID:Therapeutic drug monitoring in children with HIV/AIDS. 1522 51


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