HIV inhibitors targeted at the reverse transcriptase.

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'-fluoro-2',3'-dideoxynucleosides (i.e., FLT), 2',3'-didehydro-2',3'-dideoxynucleosides (i.e., D4C, D4T) and carbocyclic derivatives thereof (i.e., carbovir), 2'-fluoro-ara-2',3'-dideoxynucleosides, 1,3-dioxolane derivatives (i.e., 2',3'-dideoxyl-3'-thiacytidine), oxetanocin analogues and carbocyclic derivatives thereof (i.e., cyclobut-G) and the 9-(2-phosphonylmethoxyethyl)adenine (PMEA) and 9-(3-fluoro-2-phosphonylmethoxypropyl)adenine (FPMPA) derivatives. These compounds need to be phosphorylated intracellularly to their triphosphate forms before they act as competitive inhibitors or alternate substrates (chain terminators) of HIV RT. The second group includes the tetrahydro-imidazo[4,5,l-jk][1,4]-benzodiazepin-2(1H)one (TIBO), 1-[(2-hydroxyethoxy)-methyl]-6-(phenylthio)thymine (HEPT), dipyrido[3,2-b:2',3'-e]-[1,4]diazepin-6-one (nevirapine) and pyridin-2(1H)one derivatives, which interact as such, noncompetitively, with a specific allosteric binding site of HIV-1 RT. Compounds belonging to the two different groups may give rise to synergism which combined, and, likewise, viral resistance to the compounds may arise through different mutations, depending on the nature of the compounds and the group to which they belong.

authors

De Clercq E

doi

10.1089/aid.1992.8.119

subject

Has Abstract

pub_date

1992-02-01 00:00:00

pages

119-34

issue

2

eissn

0889-2229

issn

1931-8405

journal_volume

8

pub_type

杂志文章,评审
  • Abortive infection in HeLaCD4 cells by a primary HIV type 1 isolate: implications for differential host cell tropism.

    abstract::The emergence of T cell-tropic, syncytium-inducing (T-tropic/SI) HIV-1 variants from the background of macrophage-tropic, non-syncytium-inducing (M-tropic/NSI) strains is associated with disease progression in infected individuals. HIV89.6 is a primary isolate with a transitional phenotype: like M-tropic strains it re...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.1997.13.759

    authors: Smyth RJ,Yi Y,Kim FM,Collman RG

    更新日期:1997-06-10 00:00:00

  • Novel deletion of HIV type 1 reverse transcriptase residue 69 conferring selective high-level resistance to nevirapine.

    abstract::A novel deletion of residue 69 of the HIV-1 reverse transcriptase (RT) gene was detected in combination with mutations V75I/V and F77L/F in a patient with partial virological response to several antiretroviral drug regimens, including stavudine (D4T), didanosine (DDI), lamivudine (3TC), saquinavir (SQV), and nevirapin...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/088922201750461366

    authors: Suzuki K,Kaufmann GR,Mukaide M,Cunningham P,Harris C,Leas L,Kondo M,Imai M,Pett SL,Finlayson R,Zaunders J,Kelleher A,Cooper DA

    更新日期:2001-09-01 00:00:00

  • Lower Frailty Is Associated with Successful Cognitive Aging Among Older Adults with HIV.

    abstract::Aging with HIV poses unique and complex challenges, including avoidance of neurocognitive disorder. Our objective here is to identify the prevalence and predictors of successful cognitive aging (SCA) in a sample of older adults with HIV. One hundred three HIV-infected individuals aged 50 and older were recruited from ...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/AID.2016.0189

    authors: Wallace LM,Ferrara M,Brothers TD,Garlassi S,Kirkland SA,Theou O,Zona S,Mussini C,Moore D,Rockwood K,Guaraldi G

    更新日期:2017-02-01 00:00:00

  • Efficacy of epoetin alfa administered every 2 weeks to maintain hemoglobin and quality of life in anemic HIV-infected patients.

    abstract::Anemia, a common hematological abnormality in HIV, contributes to decreased quality of life (QOL). This study assessed once-every-2-week epoetin alfa on maintaining QOL and hemoglobin (Hb) in anemic HIV-infected patients in a 24-week, open-label, multicenter study. HIV-infected patients (Hb < or =12 g/dl) received epo...

    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.2006.0200

    authors: Levine AM,Salvato P,Leitz GJ,Champs 2 Study Group.

    更新日期:2008-02-01 00:00:00

  • A high frequency of defective vif genes in peripheral blood mononuclear cells from HIV type 1-infected individuals.

    abstract::We studied the heterogeneity and intactness of the vif gene in six HIV-1-infected individuals at various clinical stages. The proviral vif sequences in peripheral blood mononuclear cells were amplified by PCR, followed by cloning and sequencing of 45 vif clones. The intraindividual diversity of the vif genes ranged fr...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.1996.12.1543

    authors: Tominaga K,Kato S,Negishi M,Takano T

    更新日期:1996-11-01 00:00:00

  • HIV-specific IgG in cervicovaginal secretions of exposed HIV-uninfected female sexual partners of HIV-infected men.

    abstract::The presence of human immunodeficiency virus (HIV)-specific antibodies was examined in plasma and cervicovaginal (mucosal) samples of 24 HIV-exposed uninfected (EU) female sexual partners of HIV-infected men, and compared with findings in 18 HIV-infected and 15 low-risk HIV-uninfected women. Only HIV-infected women ha...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/08892220152741388

    authors: Buchacz K,Parekh BS,Padian NS,van der Straten A,Phillips S,Jonte J,Holmberg SD

    更新日期:2001-12-10 00:00:00

  • Near full-length sequence of HIV type 1 subtype J strain 04CMU11421 from Cameroon.

    abstract::Although Cameroon, in west central Africa, has a relatively low HIV prevalence of 5-6%, all HIV-1 groups (M, N, O, and P), nearly all HIV-1 group M subtypes, and numerous intersubtype recombinant forms have been identified in Cameroon. In this report, we describe the near full-length sequence of 04CMU11421, an HIV-1 g...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.2009.0305

    authors: Yamaguchi J,Vallari A,Ngansop C,Makamche F,Ndembi N,Mbanya D,Kaptué L,Gürtler LG,Devare SG,Brennan CA

    更新日期:2010-06-01 00:00:00

  • Mother-to-child HIV type 1 transmission in Argentina: BF recombinants have predominated in infected children since the mid-1980s.

    abstract::The molecular epidemiology of HIV-1 in Argentina is more complex than was previously appreciated. One circulating recombinant form, CRF12_BF, and many related BF recombinant forms predominate in the capital city, Buenos Aires. This study of HIV-1 subtypes acquired perinatally between 1984 and 2000 has permitted, for t...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/088922202317406619

    authors: Gomez Carrillo M,Avila M,Hierholzer J,Pando M,Martinez PL,McCutchan FE,Carr JK

    更新日期:2002-05-01 00:00:00

  • The relationship between HIV type 1 disease progression and V3 serotype in a rural Ugandan cohort.

    abstract::Antigenic properties of the V3 region are reflected by HIV-1 serotypes. These may represent biological properties of the virus. We serotyped HIV-1 in 142 serum samples from participants in a rural Uganda cohort who seroconverted between August 1991 and December 2001. Clinical progression was assessed using Cox proport...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.2004.20.932

    authors: Senkaali D,Muwonge R,Morgan D,Yirrell D,Whitworth J,Kaleebu P

    更新日期:2004-09-01 00:00:00

  • Short communication: reversible mitochondrial respiratory chain impairment during symptomatic hyperlactatemia associated with antiretroviral therapy.

    abstract::Direct evidence confirming the hypothesis that a dysfunction of the mitochondrial respiratory chain (MRC) underlies the pathogenesis of hyperlactatemia associated with highly active antiretroviral therapy (HAART) is scarce. We studied mitochondrial DNA (mtDNA) content and MRC function in the skeletal muscle of an HIV-...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/088922203322588387

    authors: Miró O,López S,Martínez E,Rodríguez-Santiago B,Blanco JL,Milinkovic A,Miró JM,Nunes V,Casademont J,Gatell JM,Cardellach F

    更新日期:2003-11-01 00:00:00

  • Impact of sampling density on the extent of HIV clustering.

    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

    authors: Novitsky V,Moyo S,Lei Q,DeGruttola V,Essex M

    更新日期:2014-12-01 00:00:00

  • Distinct populations of human immunodeficiency virus type 1 in blood and cerebrospinal fluid.

    abstract::The nucleotide sequence of the gp41 transmembrane protein coding region of human immunodeficiency virus type 1 (HIV-1) proviral DNA obtained from blood and cerebrospinal fluid (CSF) from 6 individuals was determined by direct sequencing of polymerase chain reaction (PCR)-amplified DNA. The direct sequencing approach w...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.1992.8.53

    authors: Steuler H,Storch-Hagenlocher B,Wildemann B

    更新日期:1992-01-01 00:00:00

  • HIV type 1-mediated downregulation of HLA-B*57/B*5801 proteins on elite suppressor CD4+ T cells.

    abstract::Elite controllers or suppressors (ES) are HIV-1-infected patients who maintain viral loads of <50 copies/ml without antiretroviral therapy. While HLA-B*57 and B*5801 alleles are overrepresented in ES, many HLA-B*57/B*5801 patients become chronic progressors (CP). We show here that HIV-1 infection results in similar le...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.2010.0144

    authors: Sampah ME,Ceccato CM,Blankson JN

    更新日期:2011-02-01 00:00:00

  • Molecular characterization of a recombinant HIV type 1 isolate (A/G/E/?): unidentified regions may be derived from parental subtype E sequences.

    abstract::Recombination is one of several factors contributing to the genetic diversity of HIV-1, which is divided into group M (itself comprising 11 subtypes, A-K) and two other groups named O and N. In the present study, the full-length genome of an HIV-1 isolate obtained from a Greek subject (GR17) infected in the Democratic...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/08892220050042783

    authors: Paraskevis D,Magiorkinis M,Paparizos V,Pavlakis GN,Hatzakis A

    更新日期:2000-06-10 00:00:00

  • Membrane-interactive phospholipids inhibit HIV type 1-induced cell fusion and surface gp160/gp120 binding to monoclonal antibody.

    abstract::Membrane-interactive phospholipids (PLs), previously evaluated for activity against HIV-1 in vitro, are known to affect late steps in viral replication. Studies were done to determine the effects of PL analogs on post-translational processing of HIV-1 proteins, binding of viral surface gp160/gp120 to CD4 receptor, and...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.1995.11.705

    authors: Krugner-Higby L,Goff D,Edwards T,Iyer N,Neufeld J,Kute T,Morris-Natschke S,Ishaq K,Piantadosi C,Kucera LS

    更新日期:1995-06-01 00:00:00

  • Genetic and Phenotypic Analysis of CRF01_AE HIV-1 env Clones from Patients Residing in Beijing, China.

    abstract::CRF01_AE is one of the four dominant HIV-1 strains circulating in China. In this study, we performed genetic and phenotypic analyses using a total of 60 full-length envelope gene clones from 14 HIV-1-infected individuals in the Beijing area. Among the 60 sequences analyzed, 32 have a complete open reading frame (ORF),...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/AID.2015.0377

    authors: Chen D,He X,Ye J,Zhao P,Zeng Y,Feng X

    更新日期:2016-10-01 00:00:00

  • Short communication: dynamic constraints on the second phase compartment of HIV-infected cells.

    abstract::The cells responsible for the second phase decay of HIV-1 viremia following the initiation of antiretroviral therapy have yet to be identified. A dynamic model that considers where drugs act in the virus life cycle places constraints on candidate cell types. In this regard, the rapid drop in viremia in patients starti...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/AID.2010.0199

    authors: Spivak AM,Rabi SA,McMahon MA,Shan L,Sedaghat AR,Wilke CO,Siliciano RF

    更新日期:2011-07-01 00:00:00

  • Inhibition of HIV type 1 RNA dimerization by antisense DNA corresponding to the 17-nucleotide sequence downstream from the splice donor site of HIV type 1 RNA.

    abstract::HIV-1 RNA dimerization involves at least two key regions, one located upstream from the splice donor (SD) site, and the other located downstream from the SD site. To determine the precise location and the mechanism of action of the downstream region, we constructed a model system using a synthetic HIV-1 RNA fragment (...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.1997.13.865

    authors: Zhang S,Hara H,Kaji H,Kaji A

    更新日期:1997-07-01 00:00:00

  • Inhibition of HIV type 1 replication by human T lymphotropic virus types 1 and 2 Tax proteins in vitro.

    abstract::Patients with HIV-1 and human T-lymphotropic virus type 2 (HTLV-2) coinfections often exhibit a clinical course similar to that seen in HIV-1-infected individuals who are long-term nonprogressors. These findings have been attributed in part to the ability of HTLV-2 to activate production of antiviral chemokines and to...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.2013.0027

    authors: Barrios CS,Castillo L,Giam CZ,Wu L,Beilke MA

    更新日期:2013-07-01 00:00:00

  • Antiretroviral treatment and osteonecrosis in patients of the Swiss HIV Cohort Study: a nested case-control study.

    abstract::We examined risk factors for avascular bone necrosis (AVN) particularly focusing o the question of whether antiretroviral treatment (ART) is associated with the emergence of osteonecrosis. After 11 years of following the entire cohort, 26 patients were found to have AVN. Compared to 260 concurrent HIV-infected control...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.2004.20.909

    authors: Hasse B,Ledergerber B,Egger M,Flepp M,Bachmann S,Bernasconi E,Egger M,Guyot S,Hirschel B,Weber R,Günthard HF,Swiss HIV Cohort Study.

    更新日期:2004-09-01 00:00:00

  • HIV-1 subtype C reverse transcriptase sequences from drug-naive pregnant women in South Africa.

    abstract::The HIV-1 reverse transcriptase genes from 37 HIV-1-positive pregnant women attending an antenatal clinical in Soweto, South Africa were sequenced and analyzed for the presence of drug resistance mutations. All women were antiretroviral drug naive, but were being screened as potential participants in clinical trials o...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/088922202753747950

    authors: Pillay C,Bredell H,McIntyre J,Gray G,Morris L

    更新日期:2002-05-20 00:00:00

  • Identification and characterization of the Bel 3 protein of human foamy virus.

    abstract::The human foamy virus (HFV) is a complex retrovirus that contains several regulatory and auxiliary bel genes besides the gag, pol, and env genes. In contrast to the gene products of bel 1 and bel 2/bet that were identified previously, the Bel 3 protein has not been described to date. Here we report the identification ...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.1994.10.595

    authors: Weissenberger J,Flügel RM

    更新日期:1994-05-01 00:00:00

  • Detection of anti-human cell antibodies in sera from macaques immunized with whole inactivated virus.

    abstract::More than 200 sera from macaques immunized with several different vaccine preparations were tested in various assays with cells of human and macaque origin. Only in instances where whole inactivated SIV preparations were used for immunization, were reactivities found with normal human cells, and this was the case in e...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.1992.8.1641

    authors: Langlois AJ,Weinhold KJ,Matthews TJ,Greenberg ML,Bolognesi DP

    更新日期:1992-09-01 00:00:00

  • Endemic transmission of HTLV type II among Kayapo Indians of Brazil.

    abstract::Serological studies on 926 blood samples from 703 Brazilian Kayapo (Cayapo) Indians showed, by conventional definition of HTLV seropositivity, a 28% prevalence of human T lymphotropic virus (HTLV) infection, the highest yet reported. Immunoblot (WB) and SYNTH-EIA patterns indicate that the predominant infecting agent ...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.1994.10.1165

    authors: Black FL,Biggar RJ,Neel JV,Maloney EM,Waters DJ

    更新日期:1994-09-01 00:00:00

  • Characterization of the secreted, native gp120 and gp160 of the human immunodeficiency virus type 1.

    abstract::We have previously shown that the cell line 6D5(451) chronically infected with the HIV-1 isolate HTLV-III(451), secretes the HIV-1 envelope glycoproteins gp120 and gp160 in the extracellular medium. The HTLV-III(451) gp120 and gp160 were purified by sequential affinity chromatographic steps using a monoclonal antibody...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/aid.1990.6.371

    authors: Kalyanaraman VS,Rodriguez V,Veronese F,Rahman R,Lusso P,DeVico AL,Copeland T,Oroszlan S,Gallo RC,Sarngadharan MG

    更新日期:1990-03-01 00:00:00

  • Understanding factors that modulate HIV infection at the female genital tract mucosae for the rationale design of microbicides.

    abstract::Women are now becoming the pivot of the epidemiological spread of HIV infection worldwide, especially in developing countries. Therefore, research to develop an efficient microbicide is now a priority for the prevention of HIV-1 acquisition in exposed women. However, recent disappointing failures in microbicide clinic...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/AID.2012.0049

    authors: Saidi H,Jenabian MA,Belec L

    更新日期:2012-11-01 00:00:00

  • Sequence specificity of the human immunodeficiency virus type 2 (hiv-2) long terminal repeat u3 region in vivo allows subtyping of the principal hiv-2 viral subtypes a and b.

    abstract::Sequences from the nef/LTR overlap region of the human immunodeficiency virus type 2 (HIV-2) genome were amplified from uncultured peripheral blood mononuclear cells (PBMCs) from 40 HIV-2-infected individuals in The Gambia, West Africa. Additional sequences from the plasma of three blood donors were also derived. Anal...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/088922201750063197

    authors: Berry N,Ariyoshi K,Balfe P,Tedder R,Whittle H

    更新日期:2001-02-10 00:00:00

  • Assessment of type 1 and type 2 cytokines in HIV type 1-infected individuals: impact of highly active antiretroviral therapy.

    abstract::Although the effect of highly active antiretroviral therapy (HAART) on HIV-1 replication has been established, the mechanisms involved in restoration of immune responses and reconstitution remain unknown. This study provides evidence of changes in expression of type 1 and type 2 cytokine-specific mRNA occurring during...

    journal_title:AIDS research and human retroviruses

    pub_type: 杂志文章

    doi:10.1089/088922299309784

    authors: Imami N,Antonopoulos C,Hardy GA,Gazzard B,Gotch FM

    更新日期:1999-11-20 00:00:00

  • Immune restoration by combination of a cytostatic drug (hydroxyurea) and anti-HIV drugs (didanosine and indinavir).

    abstract::Cell activation is essential for HIV infection. CD4+ T lymphocyte activation allows virus replication and CD8+ T lymphocyte activation may contribute to pathogenesis. We combined hydroxyurea, a cytostatic drug that inhibits cell activation and proliferation, with two drugs that inhibit HIV (didanosine and indinavir), ...

    journal_title:AIDS research and human retroviruses

    pub_type: 临床试验,杂志文章

    doi:10.1089/088922299310917

    authors: Lori F,Jessen H,Lieberman J,Clerici M,Tinelli C,Lisziewicz J

    更新日期:1999-05-01 00:00:00

  • Binding of NF-kB to the HIV-1 LTR is not sufficient to induce HIV-1 LTR activity.

    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

    authors: Doppler C,Schalasta G,Amtmann E,Sauer G

    更新日期:1992-02-01 00:00:00