Abstract:
:Maraviroc (MVC) is an allosteric inhibitor of human immunodeficiency virus type 1 (HIV-1) entry, and is the only CCR5 antagonist licensed for use as an anti-HIV-1 therapeutic. It acts by altering the conformation of the CCR5 extracellular loops, rendering CCR5 unrecognizable by the HIV-1 envelope (Env) glycoproteins. This study aimed to understand the mechanisms underlying the development of MVC resistance in HIV-1-infected patients. To do this, we obtained longitudinal plasma samples from eight subjects who experienced treatment failure with phenotypically verified, CCR5-tropic MVC resistance. We then cloned and characterized HIV-1 Envs (n = 77) from plasma of pretreatment (n = 36) and treatment failure (n = 41) samples. Our results showed variation in the magnitude of MVC resistance as measured by reductions in maximal percent inhibition of Env-pseudotyped viruses, which was more pronounced in 293-Affinofile cells compared to other cells with similar levels of CCR5 expression. Amino acid determinants of MVC resistance localized to the V3 Env region and were strain specific. We also observed minimal cross-resistance to other CCR5 antagonists by MVC-resistant strains. We conclude that 293-Affinofile cells are highly sensitive for detecting and measuring MVC resistance through a mechanism that is CCR5-dependent yet independent of CCR5 expression levels. The strain-specific nature of resistance mutations suggests that sequence-based diagnostics and prognostics will need to be more sophisticated than simple position scoring to be useful for managing resistance in subjects taking MVC. Finally, the minimal levels of cross-resistance suggests that recognition of the MVC-modified form of CCR5 does not necessarily lead to recognition of other antagonist-modified forms of CCR5.
journal_name
AIDS Res Hum Retrovirusesjournal_title
AIDS research and human retrovirusesauthors
Flynn JK,Ellenberg P,Duncan R,Ellett A,Zhou J,Sterjovski J,Cashin K,Borm K,Gray LR,Lewis M,Jubb B,Westby M,Lee B,Lewin SR,Churchill M,Roche M,Gorry PRdoi
10.1089/AID.2017.0097subject
Has Abstractpub_date
2017-12-01 00:00:00pages
1220-1235issue
12eissn
0889-2229issn
1931-8405journal_volume
33pub_type
杂志文章abstract::Serum samples collected prospectively between 1982 and 1987 from a cohort of homosexual men were analyzed for HIV-1 neutralizing antibodies. Seven seroconverters who became infected between 1982 and 1984 and 12 seroprevalents who were already seropositive in 1982 remained free of AIDS. During the 6 year period, 1 sero...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1988.4.343
更新日期:1988-10-01 00:00:00
abstract::The efficacy and safety of recombinant human interferon gamma (rIFN-gamma) in the reduction of opportunistic disease in patients with advanced HIV-1 infection are assessed. A 12-month double-blind, placebo-controlled, multicenter, Phase III trial of rIFN-gamma in HIV-positive patients with CD4 < 100 x 10(9)/liter on s...
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:10.1089/088922201750251981
更新日期:2001-06-10 00:00:00
abstract::The incidence of anal cancer is increased in HIV-infected patients compared with the general population. Risk factors associated with the anal cancer precursor, high-grade squamous intraepithelial lesion (HSIL), have not been extensively studied in an urban black population with late-stage HIV disease. We performed a ...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/AID.2018.0008
更新日期:2018-07-01 00:00:00
abstract::HIV inhibitors targeted at the virus-associated reverse transcriptase (RT) can be divided into two groups, depending on whether they are targeted at the substrate or nonsubstrate binding site. To the first group belong the 2',3'-dideoxynucleosides (i.e., DDC, DDI), 3'-azido-2',3'-dideoxynucleosides (i.e., AZT), 3'-flu...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章,评审
doi:10.1089/aid.1992.8.119
更新日期:1992-02-01 00:00:00
abstract::In Western countries, HTLV-1 infection is recognized mainly among foreigners coming from endemic areas. In contrast, HTLV-2 is found predominantly in native intravenous drug users (IDUs). Spain has experienced a large wave of immigration, which could have influenced the current prevalence and distribution of HTLV-1 an...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2006.0192
更新日期:2007-09-01 00:00:00
abstract::Bacterial vaginosis (BV) has been linked to an increased risk of human immunodeficiency virus (HIV) acquisition and transmission in observational studies, but the underlying biological mechanisms are unknown. We measured biomarkers of subclinical vaginal inflammation, endogenous antimicrobial activity, and vaginal flo...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2015.0006
更新日期:2015-11-01 00:00:00
abstract::Epstein-Barr virus (EBV) infection is associated with Burkitt's lymphoma (BL) in normal individuals and immunoblastic B cell lymphomas in immunosuppressed or HIV-infected individuals. SCID mice reconstituted with human peripheral blood leukocytes (hu-PBL-SCID) from EBV-seropositive donors also may develop spontaneous ...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章,评审
doi:
更新日期:1992-05-01 00:00:00
abstract::Liver enzyme elevations are frequently seen in patients treated with nevirapine (NVP). Both elevated NVP plasma levels and hepatitis C virus (HCV) infection seem to favor the development of NVP-related liver toxicity. We have examined variation on NVP C(trough) over time, as well as the impact of NVP C(trough) concent...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2005.21.555
更新日期:2005-06-01 00:00:00
abstract::The capacity to neutralize the human immunodeficiency virus (HIV) in vitro was examined in 52 sera obtained from 23 seropositive individuals in addition to 7 negative control sera. Neutralization was measured as the activity of a serum to protect MT-4 cells against the cytopathic effect of HTLV-IIIB. Virus neutralizat...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1987.3.157
更新日期:1987-07-01 00:00:00
abstract::The proportion of human immunodeficiency virus type 1 (HIV-1) among Vietnamese injecting drug users (IDUs) in Melbourne, Australia exceeds that of the background population. To investigate the molecular epidemiology of HIV-1 among this group, the C2-V4 region of the HIV-1 envelope was directly sequenced from 11 Vietna...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2004.20.1364
更新日期:2004-12-01 00:00:00
abstract::The majority of AIDS patients will experience some degree of dementia induced by human immunodeficiency virus (HIV-1). In this study, we report that treatment of human brain tissue with envelope gp120 of HIV-1 did not cause neuronal death but did cause astrocyte alterations and/or death. Human astrocyte cultures showe...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1993.9.439
更新日期:1993-05-01 00:00:00
abstract::Eosinophils are granulocytic leukocytes that function in both protective and pathological immune responses. They can be infected by HIV-1, but characterization of the infection has been hindered by lack of a productive cell culture model. In the present study, the unique eosinophilic cell line AML14.3D10 was used as a...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/08892220050140955
更新日期:2000-09-20 00:00:00
abstract::We investigated whether V3-binding assays might be useful to analyze human immunodeficiency virus type 1 (HIV-1) variants in different geographic regions. We showed that strong cross-reactivity between subtype-specific V3 peptides is almost inevitable in standard indirect enzyme-linked immunosorbent assays (EIA), impa...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1996.12.1279
更新日期:1996-09-01 00:00:00
abstract::Vaginal SHIVSF162P3 acquisition in pigtail macaques (Macaca nemestrina) is dependent on time point during the menstrual cycle. Susceptibility is higher around menstruation and lower at ovulation in mid cycle. This complicates the design of repeat low-dose (RLD) SHIV exposure studies because virus challenges given duri...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/AID.2014.0373
更新日期:2015-11-01 00:00:00
abstract::Several regulatory sequences have been characterized in the HTLV-I promoter. We report here identification of a sequence element downstream of the transcriptional start site within the first 52 nucleotides of the 5' R region, which acts negatively on the activity of the HTLV-I promoter. Determination of the half-lives...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1995.11.1123
更新日期:1995-09-01 00:00:00
abstract::Current methods to detect intraclade HIV dual infection are poorly suited for determining its prevalence in large cohorts. To investigate the potential of ultra-deep sequencing to screen for dual infection, we compared it to bulk sequence-based synonymous mixture index and the current standard of single genome sequenc...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2010.0042
更新日期:2010-12-01 00:00:00
abstract::SIVsmmFGb is a lentivirus swarm that induces neuropathology in over 90% of infected pigtailed macaques and reliably models central nervous system HIV infection in people. We have previously studied SIVsmmFGb genetic diversity and compartmentalization during acute infection, but little is understood about diversity and...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2009.0168
更新日期:2010-06-01 00:00:00
abstract::The aim of this study was to determine the patterns of change in body fat and metabolic parameters in a South African cohort on a first line ART regimen containing stavudine. Fasting lipogram, blood glucose and insulin levels, CD4 cell count, viral load, BMI, waist-to-hip ratio (WHR), and skinfold thickness at the tri...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2008.0308
更新日期:2009-08-01 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::HIV-1 protease activity is essential for viral replication. In spite of the high rates of HIV mutation, the active site of protease (residues 24-29) is a conserved site, where mutations have not been previously described. To determine the effect of mutations at positions T26 and A29 of the viral protease and its viabi...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2004.20.1183
更新日期:2004-11-01 00:00:00
abstract::Depletion of mitochondrial DNA (mtDNA) and mtDNA-encoded respiratory chain proteins in subcutaneous (SC) fat from patients with HIV lipoatrophy have clearly demonstrated the role of mitochondrial dysfunction in this syndrome. Research in HIV lipoatrophy, however, has been severely hampered by the lack of a suitable su...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2007.0262
更新日期:2008-10-01 00:00:00
abstract::Despite the success of antiretroviral therapy (ART) in decreasing mortality for HIV-1-infected patients, ART has not cured the disease. A persistent viral reservoir in the T cells of HIV patients receiving potent ART is a significant barrier preventing eradication of HIV infection. We will briefly review what is known...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章,评审
doi:10.1089/AID.2011.0017
更新日期:2011-04-01 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::We tested human immunodeficiency virus type 1 (HIV-1) antibody-positive human sera and sCD4, alone and in combination, for synergistic, additive, or antagonistic effects on blocking of HIV binding and infectivity. Data were analyzed by an application of the median effect principle derived from the law of mass action. ...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1991.7.975
更新日期:1991-12-01 00:00:00
abstract::Tuberculosis (TB) is the major opportunistic infection of HIV-infected patients in developing countries and is associated with activation of the immune system and increased HIV-1 expression. The aim of this study was to explore the biological properties of HIV-1 isolates from patients with active TB. Ten HIV-1 subtype...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/088922201750236979
更新日期:2001-05-20 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::The virucidal efficacy of various commercially available contact lens care cleaning regimens on human immunodeficiency virus (HIV-1) contaminated contact lenses using either cursory or meticulous cleaning with a rubber policeman was evaluated. Levels of infectious HIV-1 remaining on individual contact lenses were dete...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.1991.7.403
更新日期:1991-04-01 00:00:00
abstract::High level of HIV prevalence was found in some specific areas or populations in China. Shijingshan district was one of the areas with rapid increase of newly reported HIV cases in Beijing, China. Comprehensive investigation on HIV genetic characteristics is necessary in the district. In this study, we enrolled 223 new...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/AID.2018.0263
更新日期:2019-05-01 00:00:00
abstract::Human immunodeficiency virus type 1 (HIV-1) isolates differ in their use of coreceptors to enter target cells. This has important implications for both viral pathogenicity and susceptibility to entry inhibitors, recently approved or under development. Predicting HIV-1 coreceptor usage on the basis of sequence informat...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2008.0039
更新日期:2009-03-01 00:00:00
abstract::Maraviroc (MVC) is licensed in clinical practice for patients with R5 virus and virological failure; however, in anecdotal reports, dual/mixed viruses were also inhibited. We retrospectively evaluated the evolution of HIV-1 coreceptor tropism in plasma and peripheral blood mononuclear cells (PBMCs) of an infected adol...
journal_title:AIDS research and human retroviruses
pub_type: 杂志文章
doi:10.1089/aid.2014.0124
更新日期:2014-12-01 00:00:00