Abstract:
:The efficacy, safety, and pharmacokinetics of three doses of tipranavir/ritonavir (TPV/r) in highly treatment-experienced human immunodeficiency virus (HIV)-1-infected patients with protease inhibitor (PI)-resistant isolates were evaluated. A 24-week multicenter, double-blind, randomized, dose-finding trial was conducted. All patients were three-drug class experienced and had taken at least two PI-based regimens. All had at least one primary PI mutation and had plasma HIV-RNA > 1000 copies/ml. Patients remained on their background non-PI antiretroviral medications for the first 14 days. After this 14-day period of functional TPV/r monotherapy, the background antiretroviral medications were optimized based on treatment history and the screening genotype. A total of 216 patients were randomized. All groups [TPV/r 500 mg/100 mg (n = 73), 500 mg/200 mg (n = 72), and 750 mg/200 mg (n = 71) twice daily] achieved an approximate 1 log10 reduction in the median HIV-RNA at week 2. A significant reduction was sustained through 24 weeks in the TPV/r 500 mg/200 mg and 750 mg/200 mg groups. The 500 mg/200 mg dose achieved optimal median TPV trough concentrations and lower interpatient variability. The most frequently reported adverse events (AEs) were diarrhea, nausea, vomiting, fatigue, and headache. The TPV/r 750 mg/200 mg group had the highest rate of grade 3 or 4 laboratory abnormalities and study discontinuations due to AEs. All doses of TPV/r tested in this study were associated with HIV-1 viral load reductions through 24 weeks. The 500 mg/200 mg dose achieved the best efficacy, safety, and pharmacokinetic profile in this highly treatment-experienced population and was selected for the pivotal phase 3 studies.
journal_name
AIDS Res Hum Retrovirusesjournal_title
AIDS research and human retrovirusesauthors
Gathe JC Jr,Pierone G,Piliero P,Arasteh K,Rubio R,Lalonde RG,Cooper D,Lazzarin A,Kohlbrenner VM,Dohnanyi C,Sabo J,Mayers Ddoi
10.1089/aid.2006.0178subject
Has Abstractpub_date
2007-02-01 00:00:00pages
216-23issue
2eissn
0889-2229issn
1931-8405journal_volume
23pub_type
杂志文章,多中心研究,随机对照试验abstract::African monkeys can be naturally infected with SIV but do not progress to AIDS. Since mutations in the human CCR5 gene have been shown to influence susceptibility to HIV infection and disease progression, we have now investigated whether mutations in CCR5-coding sequences in African nonhuman primates can explain speci...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/088922299310647
更新日期:1999-07-01 00:00:00
abstract::We examined baseline HIV-1 protease and reverse transcriptase sequences and HIV clinical parameters from 1,021 consecutive patients (814 male, 207 female) through the Royal Perth Hospital HIV service to investigate HIV-1 subtype diversity and local phylogenetic networks from 2000 to 2014. HIV-1 subtype B virus sequenc...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/AID.2015.0206
更新日期:2016-03-01 00:00:00
abstract::Antibodies (Abs) against HLA and other cell surface molecules, which HIV-1 acquires during the budding process at the host cell surface, neutralize HIV-1 in vitro. Macaques were protected against infection by SIV grown in human cells after xenoimmunization with human MHC molecules. Besides the immune responses arising...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/088922299311051
更新日期:1999-04-10 00:00:00
abstract::In this study diverse areas of the autopsied brain of 12 HIV-infected patients with and without dementia were analyzed. All brain samples were obtained at autopsy through prior consent. Env C2-V5 region was PCR amplified and sequenced and compared between different brain regions within the same patient and also betwee...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2006.22.177
更新日期:2006-02-01 00:00:00
abstract::Both chronic hepatitis C and nevirapine (NVP) use are risk factors for transaminase elevation under highly active antiretroviral therapy. NVP is metabolized in the liver and its clearance could be altered in the presence of chronic hepatitis C virus (HCV) infection, enhancing the risk of liver toxicity. We examined NV...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/088922203763315687
更新日期:2003-03-01 00:00:00
abstract::In order to shed light on the nature of the persistent reservoir of human immunodeficiency virus type 1 (HIV-1), we investigated signs of recent evolution in the pool of proviral DNA in patients on successful HAART. Pro-viral DNA, corresponding to the C2-V3-C3 region of the HIV-1 env gene, was collected from PBMCs iso...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2006.0089
更新日期:2007-01-01 00:00:00
abstract::HIV type 1 (HIV-1) envelope glycoproteins (Env) mediate virus entry and are the target of neutralizing antibodies. Binding of the metastable HIV-1 Env trimer to the CD4 receptor triggers structural rearrangements that mediate Env conformational transitions from a closed conformation to a more open state through an int...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章,评审
doi:10.1089/AID.2018.0102
更新日期:2018-09-01 00:00:00
abstract::Identifying and monitoring HIV clusters could be useful in tracking the leading edge of HIV transmission in epidemics. Currently, greater specificity in the definition of HIV clusters is needed to reduce confusion in the interpretation of HIV clustering results. We address sampling density as one of the key aspects of...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2014.0173
更新日期:2014-12-01 00:00:00
abstract::The Kento-Mwana project was carried out in Pointe Noire, Republic of the Congo, to prevent mother-to-child HIV-1 transmission. To determine the prevalence of different subtypes and transmitted drug resistance-associated mutations, 95 plasma samples were collected at baseline from HIV-1-positive naive pregnant women en...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/AID.2015.0105
更新日期:2015-08-01 00:00:00
abstract::Two commercially available expression vectors were modified to generate plasmids pGEXcPk and pQ9cPk. Proteins expressed from pGEXcPk and pQ9cPk had a short oligopeptide tag termed Pk at their carboxy termini and either glutathione S-transferase (GST) or a small histidine (His) tag, respectively, at their N termini. GS...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1994.10.665
更新日期:1994-06-01 00:00:00
abstract::The ability to trigger an innate immune response against opportunistic pathogens associated with HIV-1 infection is an important aspect of AIDS pathogenesis. Toll-like receptors (TLRs) play a critical role in innate immunity against pathogens, but in HIV-1 patients coinfected with opportunistic infections, the regulat...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2010.0302
更新日期:2011-10-01 00:00:00
abstract::We have shown that HIV budding occurs at cholesterol-rich membrane microdomains called lipid rafts (Nguyen and Hildreth, J Virol 2000;74:3264-3272). This observation prompted us to examine the role in HIV entry of cholesterol in the membrane of cells. We recently reported that host cell cholesterol is required for HIV...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/088922203322280900
更新日期:2003-08-01 00:00:00
abstract::We studied plasma samples from 2082 Mataco Indians living in 22 different communities in the western part of Formosa Province, northern Argentina. Samples were screened for HTLV-I/II antibodies by particle agglutination assay. All positive or borderline samples were then tested by an immunofluorescence assay (IFA) on ...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/088922299311150
更新日期:1999-03-20 00:00:00
abstract::The function of the p12(I) protein of human T cell lymphotropic virus type I (HTLV-I) has been under debate. p12K (lysine) and p12R (arginine) variants of this protein at amino acid 88 and a shorter life of p12K had been reported by another group. Because HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2004.20.1092
更新日期:2004-10-01 00:00:00
abstract::Simian species of Asian and African origin are naturally infected with the simian T cell leukemia virus type I (STLV-I). Like the closely related human T cell leukemia virus type I (HTLV-I), STLV-I is primarily cell associated, and typical infections exhibit low viral burdens. Four macaques experimentally inoculated w...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1997.13.1147
更新日期:1997-09-01 00:00:00
abstract::We have evaluated the genetic diversity of HIV-1 strains infecting injecting drug users (IDUs) in Lisbon, Portugal. Heteroduplex mobility assay and/or phylogenetic analysis revealed that env (C2V3C3 or gp41) subtype B is present in 63.7% of the 135 viral samples studied, followed by subtypes G (23.7%), A (6.7%), F (5....
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/088922203766774568
更新日期:2003-06-01 00:00:00
abstract::Characterization of HIV-1 from slow progressors is important to facilitate vaccine and antiviral drug development. To identify virus attenuations that may contribute to slower rates of disease progression, the full-length viral genomes from primary isolates of six slow progressing HIV-positive children were sequenced....
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2009.0080
更新日期:2009-11-01 00:00:00
abstract::Although the breadth of the human immunodeficiency virus type 1 (HIV-1)-specific cellular immune response and its impact on the control of viral replication have already been addressed, reported data have proven controversial. We hypothesize that the nature of targeted epitopes, rather than the simple breadth or magni...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/AID.2016.0168
更新日期:2017-08-01 00:00:00
abstract::Reports indicate that myeloid and plasmacytoid dendritic cells (mDCs and pDCs), which are key effector cells in host innate immune responses, can be infected with HIV-1 and are reduced in number and function during the chronic phase of HIV disease. Furthermore, it was recently demonstrated that a sustained loss of mDC...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2009.0053
更新日期:2009-12-01 00:00:00
abstract::Human immunodeficiency virus type 1 (HIV-1) spends a significant part of its life cycle as latent provirus in nonactivated cells. It induction requires mitogen stimulation. TPA treatment induces HIV-1 transcription by protein kinase C (PKC)-mediated activation of the cellular transcription factor NF-kB. PKC activation...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1992.8.245
更新日期:1992-02-01 00:00:00
abstract::An SV40-based expression vector was used to generate CD4-negative murine L cell lines which stably expressed the human immunodeficiency virus envelope glycoprotein (env). Despite the presence of abundant intracellular envelope glycoprotein, the expression of env gp120/41 was not detected on the cell surface. Pulse-cha...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1992.8.1999
更新日期:1992-12-01 00:00:00
abstract::We examined the sera from 14 HIV-1 seroconverters for the presence of autoantibodies against CD4. Anti-CD4 antibodies were detected in the serum of 11 of 13 HIV-1-infected persons at the time of HIV-1 seroconversion. In 6 of 14 persons from whom a serum was obtained prior to HIV-1 seroconversion, anti-CD4 antibodies w...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章,多中心研究
doi:10.1089/aid.1992.8.1919
更新日期:1992-11-01 00:00:00
abstract::Lymphoid tissues are the focus of critical events in HIV pathogenesis. Persistent and high levels of virus production, extensive trapping of virus particles in germinal centers, and progressive degenerative changes in lymph node architecture are characteristics of progressive HIV-1 infection. Infiltrates of granzyme B...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/088922299311330
更新日期:1999-03-01 00:00:00
abstract::HIV-1 CRF07_BC became prevalent in Taiwan after the epidemic among injection drug users (IDUs). We describe a unique recombinant form (URF) consisting of CRF01_AE and CRF07_BC (named URF_0107-H8) genes detected from an IDU. The 8.8 kb near full-length genome of URF_0107-H8 had a CRF01_AE backbone with two CRF07_BC fra...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/AID.2015.0246
更新日期:2016-06-01 00:00:00
abstract::This randomized, open-labeled, multicenter study was designed to assess safety and pharmacokinetics of dronabinol (Marinol) tablets and megestrol acetate (Megace) micronized tablets, alone and in combination, for treatment of HIV wasting syndrome. Weight and quality of life data were also collected. Fifty-two patients...
journal_title:AIDS research and human retroviruses
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1089/aid.1997.13.305
更新日期:1997-03-01 00:00:00
abstract::The presence of transmitted drug-resistant HIV-1 (TDR) at the time of antiretroviral therapy (ART) initiation is associated with failure to achieve viral load suppression. Rates of TDR in ART-naive patients have been reported from various parts of the world through ongoing national, regional, and global evaluations; h...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/AID.2011.0386
更新日期:2013-02-01 00:00:00
abstract::Gag-specific immune responses and changes in HIV-1 RNA levels were evaluated in eight HIV-1-infected persons, in order to assess the immunotherapeutic potential HIV-1 p17/p24: Ty virus-like particles (p24-VLP). All treated subjects showed transient and dose-dependent proliferative responses to the Ty-VLP carrier (stim...
journal_title:AIDS research and human retroviruses
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1089/aid.1997.13.393
更新日期:1997-03-20 00:00:00
abstract::Alcohol use disorder (AUD) is a frequent comorbidity among people living with HIV/AIDS (PLWHA). Alcohol consumption is a significant predictor of nonadherence to antiretroviral therapy (ART), as well as worsening immunological and virological indicators among PLWHA. Clinical studies indicate that higher viral loads in...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/AID.2017.0195
更新日期:2018-02-01 00:00:00
abstract::Simian immunodeficiency virus (SIV) variant SIVsmmPBj14 is unique in producing an acutely lethal enteropathic syndrome in pigtail macaques. To determine whether the nature of the PBj14 disease would be attenuated by decreasing virus input and to relate tissue virus burden to the severity of disease, we infected pigtai...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/088922299311600
更新日期:1999-01-20 00:00:00
abstract::Many human immunodeficiency virus (HIV) proteins including Tat are produced by HIV-infected astrocytes and secreted into the brain resulting in extensive neuronal damage that contributes to the pathogenesis of HIV dementia. The neuroprotective hormone 17beta-estradiol (E2) is known to negatively regulate the HIV trans...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2009.0065
更新日期:2009-11-01 00:00:00