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41.
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Pierre Frange Marie-Laure Chaix Stéphanie Raymond Julie Galimand Christiane Deveau Laurence Meyer Cécile Goujard Christine Rouzioux Jacques Izopet the French ANRS CO PRIMO Cohort Study Group 《Journal of clinical microbiology》2010,48(10):3487-3491
We used genotypic and phenotypic assays to estimate the frequency of X4/DM viruses in 131 patients infected with non-subtype-B viruses at the time of primary HIV-1 infection (PHI). All patients were enrolled in the French PRIMO Cohort from 1996 to 2007. Most strains belonged to CRF02_AG (51.1%) and subtype A (14.5%). Sixteen viruses (12.2%) were classified as CXCR4 tropic (“X4 strains”) by the combined criteria of amino acids 11 and 25 of the V3 loop (11/25) and net charge rules and/or the SVMgeno2pheno10% algorithm: 6 strains by the combined genotypic rule, 7 by the SVMgeno2pheno10% algorithm, and 3, clustering in subtype D, by both algorithms. However, only one strain (0.8%), belonging to subtype A, was defined as a dual-tropic (DM) virus by the phenotypic assay. The 67 CRF02_AG strains included 2 classified as X4 strains by the combined genotypic rule (3%) and 2 others classified as X4 strains by SVMgeno2pheno10% (3%), but none of these 4 strains was an X4 or DM strain according to the phenotypic assay. These results suggest that the cellular virus reservoir was established with X4 strains in very few non-subtype-B-infected patients at the time of PHI. Genotypic predictions can overestimate the proportion of non-subtype-B X4 viruses at PHI.Human immunodeficiency virus type 1 (HIV-1) can be characterized by the host chemokine coreceptor that it uses to enter CD4-expressing cells. HIV-1 variants usually bind to the CCR5 chemokine coreceptor early in the course of disease. These are “R5” viruses (3, 31, 48). Viruses that use another chemokine coreceptor, CXCR4, are “X4” viruses, and they emerge later in HIV infection. They can account for up to 40 to 50% of all viruses in heavily treated patients with advanced disease (1, 32). The presence of X4 viruses has been associated with accelerated disease progression and a precipitous loss of CD4 T cells (27, 29, 40). A recent Swiss study suggested that the presence of X4 strains and the X4-specific virus load strongly predict clinical disease progression during combined antiretroviral therapy (cART), in addition to the CD4 T-cell count or viral load (44). This potential correlation between virus tropism and disease progression has important clinical implications. The development of coreceptor CCR5 antagonists for treating retroviruses and the lack of a virological response by patients infected with X4 or dual/mixed (X4/DM) viruses have increased the need to determine HIV-1 tropism.Recent studies have found the frequency of X4/DM dual-tropic strains in plasma samples from recently infected patients in the United States and Spain to be from 3.2% to 17.5% (14, 15, 16). Similarly, we found 15.9% (95% confidence interval [CI], 12.3% to 19.5%) strains of X4/DM viruses in 390 HIV-1 subtype B-infected patients diagnosed at the time of primary HIV-1 infection (PHI) in France from 1996 to 2007 (18).One of the major challenges of determining tropism is to select the best method for identifying coreceptor usage. HIV coreceptor usage is most commonly determined with a recombinant phenotype assay in clinical studies (28, 45). Bioinformatic tools based on the virus genotype may also be able to predict coreceptor usage. They are faster, less expensive, and more suitable for studies of a large number of patients than are phenotypic recombinant assays. Each available genotypic test is adequately specific but not very sensitive for detecting X4/DM or X4 variants. An overall concordance of 71.2 to 92% between genotypic and phenotypic assays has been reported (8, 15, 37, 41). However, most of these studies included HIV-1 subtype B strains. Genotypic algorithms may not be suitable for predicting the tropism of non-subtype-B HIV-1 strains (20). Two recent studies demonstrated that genotypic tests performed well for predicting the coreceptor usage of CRF02_AG and subtype C strains (36, 38), but no study has examined the correlation between genotypic and phenotypic tests for predicting the tropism of non-subtype-B HIV-1 at the time of PHI. The French PRIMO Cohort contained a large proportion of patients infected with a non-subtype-B virus (25.5% in 2005 to 2006) (6).We have therefore estimated the frequency of X4/DM viruses in 131 patients infected with non-subtype-B viruses at the time of PHI. All of them were enrolled in the French PRIMO Cohort from 1996 to 2007. We also studied the concordance between genotypic and phenotypic assays for predicting the tropism of non-subtype-B viruses in these patients. 相似文献
43.
Conor CO Reynolds M Anne Harris Kay Teschke Peter A Cripton Meghan Winters 《Environmental health : a global access science source》2009,8(1):47-19
Background
Bicycling has the potential to improve fitness, diminish obesity, and reduce noise, air pollution, and greenhouse gases associated with travel. However, bicyclists incur a higher risk of injuries requiring hospitalization than motor vehicle occupants. Therefore, understanding ways of making bicycling safer and increasing rates of bicycling are important to improving population health. There is a growing body of research examining transportation infrastructure and the risk of injury to bicyclists. 相似文献44.
为确保头抱拉定的色级在效期内符合药典标准,将主要原料7-ADCA进行精制,利用平行试验的方法,对比头孢拉定的色级及色级稳定性。用精制后的7-ADCA制成的头孢拉定色级由原来的5#降至2#,在效期内≤8#,含量几乎不变,减少了头孢拉定的退货率。 相似文献
45.
46.
Masquelier B Capdepont S Neau D Peuchant O Taupin JL Coakley E Lie Y Carpentier W Dabis F Fleury HJ;ANRS CO Aquitaine Cohort 《AIDS (London, England)》2007,21(1):103-106
We studied a case of recent infection with multidrug-resistant (MDR) HIV-1. Over 16 months off-therapy, the CD4 cell count decreased from 419 to 184 cells/mul. Antiretroviral therapy (ART) then led to an incomplete virological response but to an immunological benefit, concurrently with a shift to CCR5-only tropism and a reduction in replication capacity. ART, even if suboptimal, can be of interest in the case of MDR virus infection. 相似文献
47.
Matheron S Damond F Benard A Taieb A Campa P Peytavin G Pueyo S Brun-Vezinet F Chene G;ANRS CO HIV Cohort Study Group 《AIDS (London, England)》2006,20(3):459-462
In 61 antiretroviral-naive HIV-2-infected patients starting triple therapy at a median CD4 cell count of 136 cells/microl, the median increase was 41 cells/microl at month 12, which was no different among those on protease inhibitors or triple nucleoside analogues. Despite virological response, as the median plasma load was under the detectable threshold from month 3, CD4 cell recovery remained poor in treated HIV-2 infection. Our results raise the question of the optimal regimen to recommend in HIV-2-infected patients. 相似文献
48.
为提高精氨酸的收率和质量,我们对精氨酸的精制工艺进行研究,通过正交试验确定了最佳工艺参数,即结晶温度-5℃,溶解时间0.75hr,溶解温度65℃。采用此工艺后收率提高到90%,成本下降20元/公斤。 相似文献
49.
50.
为使抗生素发酵取得较好的效果,我们对在抗生素发酵中起重要作用的培养基进行了比较试验,对目前已有的三种培养基:麸质粉、玉米浆和药媒——2000进行分析比较,采用高效液相色谱法对其中氨基酸含量进行检测,结果表明,药媒——2000中氨基酸含量高,优于其他氮源,更适于作培养基。 相似文献