Abstract:
:Psychiatric illness is common in HIV-infected patients and underlines the importance for screening not only for cognitive impairment but also for co-morbid mental disease. The rationale for combining immunomodulatory neurokinin- 1 receptor (NK1-R) antagonists with combined antiretroviral therapy (cART) is based on multimodal pharmacologic mechanisms. The NK1-R antagonist aprepitant's potential utility as a drug for depression is complicated by >99.9% protein binding and both enzyme inhibition and induction of CYP3A4. A population-based PK model developed from a pilot Phase 1B trial in 19 HIV-infected patients (125 or 250 mg/d aprepitant for 2 weeks) was modified to account for enzyme induction and impact of an exposure enhancer on CYP3A4 metabolism. Likelihood of clinical success in depression was assessed based on achievement of target trough plasma concentration and evaluated using Monte Carlo simulation. Scenarios were generated for varying daily dose (375, 625, 750 and 875 mg), pharmacokinetic variability, exposure enhancement (EE), duration (2 and 6 months) and sample size (n=12 and 24/arm). Daily dosing of ≥ 625 mg with EE yielded desirable troughs (based on in vitro infectivity experiments) of > 2.65 ug/mL for the majority of virtual patients simulated. Results are dependent on the degree of exposure enhancement and extent of enzyme induction. Actual threshold exposure requirements for aprepitant in HIV-associated depression are unknown though preclinical evidence supports trough levels > 2.65 ug/mL. If 100% NK1r blockage is necessary for efficacy, doses of 875 mg (625 mg with EE) or higher may be required. The benefit of aprepitant on innate immunity(natural killer cells) and absence of negative effects onex vivo neutrophil chemotaxis alleviates concerns regarding drug dependent inhibition (DDI)-mediated infection risk.
journal_name
Curr HIV Resjournal_title
Current HIV researchauthors
Barrett JS,Bajaj G,McGuire J,Wu D,Spitsin S,Moorthy G,Zhao X,Tebas P,Evans DL,Douglas SDdoi
10.2174/1570162x12666140526120831subject
Has Abstractpub_date
2014-01-01 00:00:00pages
121-31issue
2eissn
1570-162Xissn
1873-4251pii
CHIVR-EPUB-60666journal_volume
12pub_type
杂志文章,随机对照试验abstract:OBJECTIVES:The aim of the study was to investigate if the supplementation with multistrain probiotics may be able to modulate T cell response in HIV-1 infected patients and to evaluate the anti-HIV activity of probiotic by studying fecal water (FW) samples. METHODS:Three HIV-1-positive patients (Pt1, Pt2 and Pt3) on l...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/1570162X17666190903230622
更新日期:2019-01-01 00:00:00
abstract::To assess the correlation between HIV-1 RNA load in blood and semen by antiretroviral therapy status and the relative penetration of antiretroviral drugs in seminal plasma. We performed a cross-sectional cohort study of 119 HIV-1 subjects divided into three groups according to treatment status. Blood and semen were co...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/157016208785861177
更新日期:2008-09-01 00:00:00
abstract::Immunization is an important measure to protect HIV-infected children and adults against certain vaccine preventable diseases. However, the antibody response, which is associated with the level of CD4+ T cell count, is frequently impaired in this group of patients. Certain vaccines enhance virus replication and transi...
journal_title:Current HIV research
pub_type: 杂志文章,评审
doi:10.2174/1570162043351084
更新日期:2004-10-01 00:00:00
abstract::An estimated 800,000 children acquired HIV-infection in 2002, most as a result of mother-to-child transmission (MTCT), and vertically-acquired HIV infection continues to be of major public health importance. Prevention of MTCT is possible with a combination of interventions including antiretroviral therapy (ART) (usua...
journal_title:Current HIV research
pub_type: 杂志文章,评审
doi:10.2174/1570162033485140
更新日期:2003-10-01 00:00:00
abstract::AIDS has claimed the lives of 25 million people worldwide, an additional 40 million people are HIV-infected and new cases are being diagnosed every year. Despite the fact that HAART has moved AIDS from the category of terminal diseases to that of treatable chronic illnesses, its long-term therapeutic success may be co...
journal_title:Current HIV research
pub_type: 杂志文章,评审
doi:10.2174/157016207781023965
更新日期:2007-07-01 00:00:00
abstract::Several studies have suggested that aerobic physical activity is safe and beneficial for HIV-infected adults. However, there is information lacking regarding whether HIV-infected patients practice physical activity and to what extent. Therefore, the aim of this systematic review was to determine the prevalence of phys...
journal_title:Current HIV research
pub_type: 杂志文章,评审
doi:10.2174/157016212802429794
更新日期:2012-09-01 00:00:00
abstract:OBJECTIVE:There is scarce information about the molecular epidemiology of HIV-infection in Armenia (former USSR). The objective of this work was to estimate the distribution of HIV-1 subtypes in this country and get any information about HIV drug resistance in naÏve patients. DESIGN:A joint study involving 78 patients...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/1570162x13666150407142834
更新日期:2015-01-01 00:00:00
abstract:BACKGROUND:Due to the persistence of latent HIV-infected cellular reservoirs, HIV virus can not be eradicated completely. OBJECTIVE:To identify proteins related to HIV latency, we performed a subcellular proteomic study in HIV latent cell lines. METHODS:An established HIV-1 latent cell model (J-Lat Tat-GFP Clone A7 c...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/1570162X17666190506155222
更新日期:2019-01-01 00:00:00
abstract::In HIV-1, tRNA(Lys3) serves as the primer for reverse transcriptase, and during viral assembly, the tRNA(Lys) isoacceptors, tRNA(Lys1,2) and tRNA(Lys3), are selectively packaged into the virion. In this review, we shall first discuss the evidence for the formation of a tRNA(Lys) packaging complex, whose components inc...
journal_title:Current HIV research
pub_type: 杂志文章,评审
doi:10.2174/1570162043484988
更新日期:2004-04-01 00:00:00
abstract::In the HAART era Kaposi's sarcoma (KS) remains the second most frequent tumor in HIV-infected patients worldwide, and it has become the most common cancer in Sub-Saharan Africa. In western countries the risk for KS in men having sex with men (MSM) is 5 to 10 times higher compared to other groups of individuals practic...
journal_title:Current HIV research
pub_type: 杂志文章,评审
doi:10.2174/157016209789973619
更新日期:2009-11-01 00:00:00
abstract::Enteroaggregative Escherichia coli (EAEC) have been isolated from both HIV-positive and non-HIV diarrheal samples. In this study a collection of 18 isolates from these two groups were compared for biofilm formation and antibiotic resistance and for the presence of 14 virulence-related genes. All the HIV-positive and o...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/1570162x12666140207161000
更新日期:2013-12-01 00:00:00
abstract:OBJECTIVE:To evaluate the potential impact of the current global economic crisis (GEC) on the spread of HIV. DESIGN:To evaluate the impact of the economic downturn we studied two distinct HIV epidemics in Southeast Asia: the generalized epidemic in Cambodia where incidence is declining and the epidemic in Papua New Gu...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/157016209789973637
更新日期:2009-11-01 00:00:00
abstract:BACKGROUND:Despite decreasing rates of HIV among many populations, HIV-related health disparities among gay, bisexual and other men who have sex with men persist, with disproportional percentages of new HIV diagnoses among racial and ethnic minority men. Despite increasing awareness of HIV pre-exposure prophylaxis (PrE...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/1570162X16666180730144455
更新日期:2018-01-01 00:00:00
abstract:BACKGROUND:Human immunodeficiency virus (HIV) infection is a global health burden which ultimately results in acquired immune deficiency syndrome (AIDS). There are multiple host factors which are capable of limiting HIV-1 replication. One of the most important host factors which inhibit HIV-1 DNA synthesis is the apoli...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/1570162X16666181018155827
更新日期:2018-01-01 00:00:00
abstract::According to the World Health Organization's 2007 estimates, close to 33 million people worldwide are living with HIV/AIDS. Over the past two decades, significant progress has been made in understanding HIV pathogenesis and disease progression, which has allowed the identification of a multitude of drug and vaccine ta...
journal_title:Current HIV research
pub_type: 杂志文章,评审
doi:10.2174/157016208785861159
更新日期:2008-09-01 00:00:00
abstract::In HIV-1 infected cells, over 40 different mRNA species are produced by alternative splicing of the single HIV-1 primary RNA transcript. In addition, approximately half of the HIV-1 primary RNA transcripts are not spliced and are exported to the cytoplasm where they serve as mRNA and as genomic RNA. In this article, w...
journal_title:Current HIV research
pub_type: 杂志文章,评审
doi:10.2174/157016206775197655
更新日期:2006-01-01 00:00:00
abstract::The aim of the study was to report the epidemiological profile of HIV-1 positive patients from, Istanbul, Turkey, which has one of the lowest HIV-1/AIDS prevalences in Europe. The patients were followed by ACTHIV-IST group which was established by the Infectious Diseases Departments of five teaching hospitals (three u...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/1570162x12666140411111803
更新日期:2014-01-01 00:00:00
abstract:OBJECTIVE:Since 2010, Nigeria has adopted World Health Organization (WHO) 'Option B' which requires administration of triple antiretroviral prophylaxis or treatment (ART) to all HIVinfected pregnant women. We studied the transmission outcomes of HIV-exposed children up to 18 months of age. DESIGN:This was a retrospect...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/1570162x1303150506182534
更新日期:2015-01-01 00:00:00
abstract:OBJECTIVE:Identifying the genetic variability in vertically transmitted viruses in early infancy is important to understand the disease progression. Being important in HIV-1 disease pathogenesis, vpu gene, isolated from young infants was investigated to understand the viral characteristics. METHOD:Blood samples were o...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/1570162X16666180219154601
更新日期:2018-01-01 00:00:00
abstract:BACKGROUND:Manipur is one of the highest HIV prevalence states of India because of its geographical location at the international border near the golden triangle of South-East Asia, but no study on drug resistance associated mutations (DRAMs) has been reported yet. OBJECTIVE:A population-based study on DRAMs of HIV-1 ...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/1570162x14666160401131426
更新日期:2016-01-01 00:00:00
abstract::Previous studies have demonstrated that nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) act as chemical enhancers of human immunodeficiency virus type 1 (HIV-1) RT dimerization. In the current study, we sought to define the role of key residues (101, 103, 108, 181, 188, 190, 225 and 318) in the NNRTI-bind...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/157016208783885065
更新日期:2008-03-01 00:00:00
abstract:BACKGROUND:Human milk banking has been promoted to provide donated breast milk for at-risk children whose mothers cannot breastfeed them but this effort was hindered by the advent of HIV epidemic. OBJECTIVE:To estimate the seroprevalence of HIV, syphilis and hepatitis B in the blood of human milk donors registered in ...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/1570162X15666170707143541
更新日期:2017-01-01 00:00:00
abstract::VGV-1, a clinical-grade formulation of bovine thymus nuclear protein (TNP) has been demonstrated to possess anti-viral activity in HIV-1 patients in five clinical trials, one of which was placebo controlled double-blinded. However, to date molecular mechanisms remain to be identified. Using surface plasmon resonance w...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/157016208785132545
更新日期:2008-06-01 00:00:00
abstract::Drug use and HIV/AIDS are global public health issues. The World Health Organization (WHO) estimates that up to 30% of HIV infections are related to drug use and associated behaviors. The intersection, of the twin epidemics of HIV and drug/alcohol use, results in difficult medical management issues for the health care...
journal_title:Current HIV research
pub_type: 杂志文章,评审
doi:10.2174/157016209788680598
更新日期:2009-07-01 00:00:00
abstract:BACKGROUND:Vaccine against HIV-1 is not currently available. In present, Virus like particles (VLPs) as effective strategy was used in several vaccine developing. Two conserved sequences; V3 loop of gp120 and the membrane-proximal external region (MPER) of gp41 are dominant sites for vaccine studies. OBJECTIVE:In this...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/1570162X15666171017122229
更新日期:2017-01-01 00:00:00
abstract::Opioid use in HIV infection has been associated with an increased frequency of neurological disease and cognitive impairment and vitamin A deficiency has been linked to progressive HIV disease in drug users. In this report the potential effects of these factors, alone and in combination, on gamma amino butyric acid (G...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/157016212802138715
更新日期:2012-07-01 00:00:00
abstract:BACKGROUND:HIV infection induces alterations in the gut-associated lymphoid tissue (GALT) that constitutes the most important site for viral replication due to the extensive presence of effector memory T-cells. In the case of HIV-controllers, several studies have reported fewer peripheral alterations and conserved immu...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/1570162X17666190130115113
更新日期:2018-01-01 00:00:00
abstract::The oral cavity of human immunodeficiency virus type I (HIV-1) infected individuals is subjected to a series of opportunistic infections which are usually considered as a prognostic marker for the severity of infection as well as an indicator of immunodeficiency. The highly active antiretroviral therapy (HAART) has si...
journal_title:Current HIV research
pub_type: 杂志文章,评审
doi:10.2174/157016207780636533
更新日期:2007-05-01 00:00:00
abstract::A current debate in the HIV-1 vaccine field concerns the ability of an immunodeficiency virus to elicit a protective response. One argument is that HIV-1 superinfections are frequent in healthy individuals, because virus evades conventional immune surveillance, a serious obstacle to vaccine design. The opposing argume...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/157016209789346255
更新日期:2009-09-01 00:00:00
abstract:BACKGROUND:Vitamin D deficiency is common in HIV population and has been associated with increased comorbidity risk and poor immunologic status. OBJECTIVE:To evaluate the effect of protease inhibitor lopinavir/ritonavir monotherapy on changes in serum 25-hydroxyvitamin D [25(OH)D] over 48 weeks. METHODS:Thirty-four t...
journal_title:Current HIV research
pub_type: 杂志文章
doi:10.2174/1570162X18666200827115615
更新日期:2020-08-27 00:00:00