Abstract:
BACKGROUND:We aimed to investigate the extent of pharmacokinetic drug interactions between bosentan and a fixed combination of lopinavir/ritonavir. METHODS:This was a three-way crossover study in 12 healthy male participants treated with bosentan (125 mg twice daily) and lopinavir/ritonavir (400/100 mg twice daily) alone or in combination for 9.5 days. RESULTS:Combination treatment resulted in slightly lower area under the concentration-time curve during the 12 h dosing interval under steady-state conditions (AUC(tau,ss)) values of both lopinavir and ritonavir with geometric mean ratios (GMRs; 90% confidence intervals [CIs]) of 0.86 (0.74-0.99) for lopinavir and 0.83 (0.76-0.92) for ritonavir. The maximum concentration in steady state (C(max,ss)) of lopinavir and ritonavir remained unchanged with a GMR of 0.95 and 1.01, respectively, and the 90% CIs were within the range of 0.8-1.25. The observed effects of bosentan on lopinavir and ritonavir pharmacokinetics were considered to be not clinically relevant. The pharmacokinetics of bosentan were strongly affected by coadministration. Bosentan concentration increased up to 48-fold during the first 4 days of coadministration with lopinavir/ritonavir. At steady state, the GMR for AUC(tau,ss) was 5.22 (3.84-7.10) and for C(max,ss) was 6.12 (4.24-8.82). The increased exposure to bosentan was reflected in an increase in adverse events attributed to bosentan, that is, mainly headache, but not in liver enzyme abnormalities. CONCLUSIONS:Bosentan does not affect lopinavir and ritonavir exposure to a clinically relevant extent, but tolerability of bosentan should be monitored in HIV patients under antiretroviral therapy with lopinavir/ritonavir. It is anticipated that all ritonavir-boosted protease inhibitors will have a similar effect on bosentan pharmacokinetics.
journal_name
Antivir Therjournal_title
Antiviral therapyauthors
Dingemanse J,van Giersbergen PL,Patat A,Nilsson PNdoi
10.3851/IMP1506subject
Has Abstractpub_date
2010-01-01 00:00:00pages
157-63issue
2eissn
1359-6535issn
2040-2058journal_volume
15pub_type
杂志文章,随机对照试验abstract:BACKGROUND:US guidelines recommend genotyping for persons newly diagnosed with HIV infection to identify transmitted drug resistance mutations associated with decreased susceptibility to nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors and protease inhibitors. To date, testin...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP2780
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:Studies of the effects of antiretroviral drugs on lipid metabolism are limited by the availability of suitable models. We have thus developed an animal model utilising Göttingen mini-pigs. The normal lipid metabolism of mini-pigs closely reflects that of humans and they are expected to have similar reactions...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP1509
更新日期:2010-01-01 00:00:00
abstract::Phanuphak et al. compared three strategies for first-line antiretroviral therapy in 150 Thai patients: initiating therapy with zidovudine (AZT), tenofovir disoproxil fumarate (TDF), or a 24-week lead-in phase with stavudine (d4T) followed by a switch to AZT. Those taking d4T had higher haemoglobin levels and CD4(+) T-...
journal_title:Antiviral therapy
pub_type: 评论,杂志文章
doi:10.3851/IMP2498
更新日期:2012-01-01 00:00:00
abstract:BACKGROUND:Potential drug-drug interactions (PDDIs) might expand with new combination antiretroviral therapies (ART) and polypharmacy related to increasing age and comorbidities. We investigated the prevalence of comedications and PDDIs within a large HIV cohort, and their effect on ART efficacy and tolerability. METH...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP1540
更新日期:2010-01-01 00:00:00
abstract:OBJECTIVE:In patients with a chronic asymptomatic HIV-1 infection and >200 CD4+ T-cells/microl, the optimal timing of highly active antiretroviral therapy (HAART) initiation is unclear. It involves a trade-off between a potentially reduced risk of mortality, when started earlier in the course of infection, and an earli...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:2006-01-01 00:00:00
abstract:BACKGROUND:Researchers must often rely on creatinine measurements to assess kidney function because direct glomerular filtration rates (GFR) and cystatin-c are rarely measured in routine clinical settings. However, HIV treatments often include dolutegravir, raltegravir, rilpivirine or cobicistat, which inhibit the prox...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP3373
更新日期:2020-11-19 00:00:00
abstract:BACKGROUND:Antibodies to liver-kidney microsome type 1 (anti-LKM-1), which are a marker of autoimmune hepatitis, are found in a minority of patients with chronic hepatitis C virus (HCV) infection. Whether interferon/ribavirin therapy is safe and effective in these patients is unclear. AIM:To describe the prevalence, c...
journal_title:Antiviral therapy
pub_type: 临床试验,杂志文章
doi:
更新日期:2005-01-01 00:00:00
abstract::The balance of virus production and clearance for untreated patients with chronic hepatitis C virus (HCV) results in a decline of viraemia when initiating active antiviral treatment. During the first phase of interferon-alpha therapy, after a delay of about 8-9 h, the kinetics of the viral load is characterized by a r...
journal_title:Antiviral therapy
pub_type: 杂志文章,评审
doi:
更新日期:2000-06-01 00:00:00
abstract::MicroRNAs regulate gene expression by binding to the 3'-untranslated region (UTR) of target messenger RNAs (mRNAs). The importance of microRNAs has been shown for several liver diseases, for example, viral hepatitis. MicroRNA-122 is highly abundant in the liver and is involved in the regulation of lipid metabolism. Mi...
journal_title:Antiviral therapy
pub_type: 杂志文章,评审
doi:10.3851/IMP2766
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:A genome-wide association study revealed an association between variants of the inosine triphosphatase (ITPA) gene and ribavirin (RBV)-induced anaemia. The aim of this study was to replicate this finding in an independent Japanese cohort and to define a method to allow pretreatment prediction of anaemia in c...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP1796
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:Rilpivirine (RPV), a non-nucleoside reverse transcriptase inhibitor (NNRTI), was approved for HIV-1 infected, antiretroviral treatment-naive adults based on data from two Phase III trials. In the screening population, the prevalence of 49 NNRTI resistance-associated mutations (RAMs) and the impact of allowed...
journal_title:Antiviral therapy
pub_type: 杂志文章,随机对照试验
doi:10.3851/IMP2358
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:This study investigated survival in people living with HIV being followed-up from 5 and 10 years after antiretroviral therapy (ART) initiation in a multi-country Asian cohort. METHODS:We included patients in follow-up >5 years after ART initiation. Factors associated with mortality beyond 5 and 10 years on ...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP3358
更新日期:2020-01-01 00:00:00
abstract::Although chronic HBV infection is the leading cause of chronic liver disease and death worldwide, there are substantial differences in its clinical courses regarding prevalence, mode of transmission, characteristics of each phase, responses to antiviral therapy, and development of cirrhosis and hepatocellular carcinom...
journal_title:Antiviral therapy
pub_type: 杂志文章,评审
doi:10.3851/IMP1982
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:Drug efflux (for example, P-glycoprotein [P-gp], multidrug resistance-associated proteins [MRPs] and breast cancer resistance protein [BCRP]) and influx (for example, human organic anion transporting polypeptide [hOCTP] or human organic anion transporting polypeptide [hOATP]) transporters alter the cellular ...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP1399
更新日期:2009-01-01 00:00:00
abstract::Antiretroviral treatment with three nucleoside reverse transcriptase inhibitors (NRTIs) is widely used, but the combination of abacavir, didanosine and stavudine has never been investigated. We describe the surprising and consistent genotypic and phenotypic outcome in patients failing this combination. As part of a Da...
journal_title:Antiviral therapy
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:
更新日期:2003-04-01 00:00:00
abstract::Human papillomavirus (HPV) infections are a major human health problem; they are the cause of recurrent benign warts and of several cancers of the anogenital tract and head and neck region. Although there are two prophylactic HPV vaccines that could, if used universally, prevent as many as two-thirds of HPV-induced ca...
journal_title:Antiviral therapy
pub_type: 杂志文章,评审
doi:10.3851/IMP2612
更新日期:2013-01-01 00:00:00
abstract:BACKGROUND:Quantification of HBsAg in serum may be of clinical importance in predicting HBsAg seroconversion and complete response to treatment. METHODS:Serum HBsAg was quantified by ADVIA Centaur in 63 patients with HBeAg-negative chronic hepatitis B (CHBe-). A total of 42 had received interferon-alpha2b (IFN-alpha2b...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:2007-01-01 00:00:00
abstract:BACKGROUND:Nucleoside (or nucleotide) reverse transcriptase inhibitors (NRTIs) cause side effects in some patients, prompting the use of either partly or fully NRTI-sparing regimens. METHODS:We used data from the Swiss HIV Cohort Study to estimate the effectiveness of two new dolutegravir dual regimens relative to the...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP3310
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:Dyslipidaemia and lipodystrophy have been described in treated HIV patients and in a small percentage of untreated HIV patients. Lipodystrophy in these patients has been shown to be associated with a lower expression of low density lipoprotein (LDL) receptors. METHODS:We have investigated the effect of anti...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:2005-01-01 00:00:00
abstract::Chronic infection with HBV or HCV can lead to the development of hepatocellular carcinoma (HCC). The major risk factors for HBV-related HCC are persistent presence of hepatitis B e antigen (HBeAg) and/or high serum HBV DNA levels, and cirrhosis. The major risk factor for HCV-related HCC is cirrhosis. One randomized do...
journal_title:Antiviral therapy
pub_type: 杂志文章,评审
doi:10.3851/IMP1895
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:Little is known about pregnancy patterns and levels of HIV RNA in HIV-infected women conceiving on highly active antiretroviral therapy (HAART) with non-suppressed viral load (VL), nor about their therapeutic management. METHODS:Linear mixed models were fitted to study changes in VL and potential associated...
journal_title:Antiviral therapy
pub_type: 杂志文章,多中心研究
doi:10.3851/IMP1489
更新日期:2010-01-01 00:00:00
abstract:BACKGROUND:In haematopoietic stem cell transplant (HSCT) recipients, cytomegalovirus (CMV) infection contributes significantly to morbidity and mortality in both the early and late post-transplant period. Ganciclovir (GCV) is the treatment of choice for CMV, but requires intravenous administration, a fact that complica...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP1858
更新日期:2011-01-01 00:00:00
abstract:BACKGROUND:Insulin resistance (IR) was one of the first reported complications in HIV-positive patients who were receiving antiretroviral therapy (ART). However, the metabolic effects of newer fixed-dose ART combinations are unclear. METHODS:This Phase I prospective randomized open-label study evaluated the effects on...
journal_title:Antiviral therapy
pub_type: 杂志文章,随机对照试验
doi:10.3851/IMP3049
更新日期:2016-01-01 00:00:00
abstract:BACKGROUND:In pregnant women taking antiretroviral treatment at conception treatment may be transiently stopped for safety concerns. Limited data are available on the consequences of such discontinuations. METHODS:We used data from a national study to compare different treatment pathways during pregnancy. Overall, 321...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:2008-01-01 00:00:00
abstract::We report the first two paediatric cases of sofosbuvir treatment during high-intensity myeloablative conditioning and engraftment phases of haematopoietic stem cell transplantation. These reports highlight the safety of sofosbuvir during all phases of transplantation and the lack of interaction between sofosbuvir and ...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP3332
更新日期:2019-01-01 00:00:00
abstract:BACKGROUND:Scavenger receptor class B type-1 (SR-B1) is one of the many receptors used by HCV to infect hepatocytes. It is used by the virus not only to directly infect cells but also to facilitate cell-to-cell transmission of the virus. Agents such as anti-human SR-B1 (anti-hSR-B1) antibodies represent potential thera...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP2570
更新日期:2013-01-01 00:00:00
abstract::The effectiveness of current antiretroviral therapies has led to more patients receiving long-term therapy, and increasing numbers of older patients. The complex interactions between HIV infection, ageing, comorbid conditions and drug-related toxicities, and their combined effects on patient health and quality of life...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP1470
更新日期:2009-01-01 00:00:00
abstract::Combinations of two nucleoside analogue reverse transcriptase inhibitors plus a third agent represent the current standard for antiretroviral therapy. Stavudine is a nucleoside analogue that demonstrates in vitro activity against human immunodeficiency virus type 1 (HIV-1) and HIV-2 within an acceptable therapeutic in...
journal_title:Antiviral therapy
pub_type: 杂志文章,评审
doi:
更新日期:1997-12-01 00:00:00
abstract:BACKGROUND:Patients infected with hepatitis C virus (HCV) who respond to treatment with interferon-alpha plus ribavirin exhibit biphasic or triphasic viral load decreases. While the rapid first phase is indicative of the effectiveness of therapy in blocking viral production (epsilon), the slope of the final phase (lamb...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:
更新日期:2009-01-01 00:00:00
abstract::Here, we describe a case of an HIV-infected patient with right lower limb oedema that appeared after initiation of tenofovir and emtricitabine treatment. The patient was fully investigated by serial heart and vessel echo-Doppler examination. Oedema of the lower limb was attributed to a transient drug-induced fivefold ...
journal_title:Antiviral therapy
pub_type: 杂志文章
doi:10.3851/IMP1302
更新日期:2009-01-01 00:00:00