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Risk of failure in patients with 215 HIV-1 revertants starting their first thymidine analog-containing highly active antiretroviral therapy 总被引:3,自引:0,他引:3
Violin M Cozzi-Lepri A Velleca R Vincenti A D'Elia S Chiodo F Ghinelli F Bertoli A d'Arminio Monforte A Perno CF Moroni M Balotta C 《AIDS (London, England)》2004,18(2):227-235
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目的分析接受一线抗病毒治疗(ART)时间较长的艾滋病(AIDS)病人,更换二线药物后的治疗效果及相关耐药位点的变化。方法在河南和安徽采用随访观察的方法,比较更换二线药物前和换药10个月左右,AIDS病人病毒及免疫学指标的变化情况。结果共调查68名AIDS病人,更换抗病毒药物前治疗时间中位数为77个月。病毒载量(VL)≥1000拷贝/mL组,在换药后病毒抑制率为79.1%(34/43),换药前后的耐药率分别为76.7%和9.3%(Pdo.05);CD+T淋巴细胞中位数分别为186个/μL和320个/μL(P〈0.05)。耐药组换药后的耐药率为11.4%(4/35),换药后病毒抑制率由换药前的5.7%上升到82.9%(P〈0.05);换药前后CD+T淋巴细胞中位数分别为187个/μL和325个/μL(P〈0.05)。换药前常见的耐药位点包括K103N、Y181C、TAMs、M184V和69位插入复合体,而换药后的蛋白酶抑制剂(PIs)突变位点为M46I。结论对于长期接受一线ART且病毒载量≥l000拷贝/mL或耐药的病人,更换二线药物后可取得较好的临床效果;而对于病毒载量〈1000拷贝/mL或非耐药的病人,如何换药仍需进一步研究。 相似文献
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Hsieh SM Chang SY Hung CC Sheng WH Chen MY Chang SC 《International journal of STD & AIDS》2011,22(11):617-620
Ritonavir-boosted tipranavir (TPV/r) and darunavir (DRV/r) have been approved in patients with virological resistance to multiple protease inhibitors (PIs). Whether the HIV-1 from these patients with virological failure to first-generation PIs remains susceptible to TPV/r or DRV/r is questionable. The susceptibilities of HIV-1 isolates to second-generation PIs in patients who experienced virological failure in three time periods were analysed: 9-2006 to 4-2007 (period 1), 5-2007 to 12-2007 (period 2) and 1-2008 to 8-2008 (period 3). A total of 53 subjects were enrolled, and 51 subject isolates (96.2%) were resistant to ≥1 PIs. The mutation scores for TPV and DRV, and the percentage of isolates with resistance to TPV or DRV, increased significantly from period 1 to period 3. Our data revealed a significant increase in the levels of genotypic resistance to TPV and DRV over the past two years in patients with virological failure to first-generation PIs. 相似文献
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Key amprenavir resistance mutations counteract dramatic efficacy of darunavir in highly experienced patients 总被引:1,自引:0,他引:1
Delaugerre C Mathez D Peytavin G Berthé H Long K Galperine T de Truchis P 《AIDS (London, England)》2007,21(9):1210-1213
In highly experienced HIV-1-infected patients, a ritonavir-boosted darunavir-containing regimen was associated with dramatic immunological and virological efficacy. Patients harbouring viruses with amprenavir-specific resistance profiles, such as I50V or V32I + I47V, failed on a darunavir/ritonavir-containing regimen. These key amprenavir mutations were also selected at the time of failure, suggesting their impact on darunavir efficacy. 相似文献
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Cozzi-Lepri A;Standardization Clinical Relevance of HIV Drug Resistance Testing Project for the Forum for Collaborative HIV Research 《HIV medicine》2008,9(1):27-40
OBJECTIVES: To investigate the concordance between any of the results of nine HIV-1 drug-resistance interpretation systems (ISs) and their ability to predict week 8 and week 24 virological responses to abacavir-containing combination therapy. PATIENTS AND METHODS: A total of 1306 HIV-infected patients with a viral load >500 HIV-1 RNA copies/mL and a baseline genotypic resistance test were included in the study. Predicted abacavir susceptibilities according to each rule-based IS were compared. Linear and logistic regressions were used to assess the prognostic value of each IS for week 8 and week 24 responses, respectively. RESULTS: A median of three (interquartile range 1-5) abacavir mutations were detected at baseline. Comparing the IS predictions for abacavir susceptibility, 9% to 45% of patients were predicted to have resistant (R) virus, 9% to 53% virus with intermediate (I) resistance, and 23% to 74% susceptible (S) virus. Overall, the median week 8 viral load reduction was 1.61 log(10) copies/mL (95% confidence interval 1.52-1.71) and 50% of patients experienced virological failure at 24 weeks. Most ISs showed better virological responses with S and I viruses than with R viruses. CONCLUSIONS: Despite some degree of variability in predicted abacavir susceptibility among ISs, most ISs are useful to predict virological response. 相似文献
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Factors associated with virological response in HIV-infected patients failing antiretroviral therapy: a prospective cohort study 总被引:1,自引:0,他引:1
Fournier S Chaffaut C Maillard A Loze B Lascoux C Gérard L Timsit J David F Bergmann JF Oksenhendler E Sereni D Chevret S Molina JM 《HIV medicine》2005,6(2):129-134
OBJECTIVES: To assess the antiviral response to optimized therapy following genotypic resistance testing and to identify factors associated with virological response in HIV-1-infected patients failing antiretroviral therapy. METHODS: A prospective cohort study was conducted in 344 HIV-1-infected patients who underwent genotypic resistance testing because of virological failure. Virological response was defined as a plasma HIV RNA level below 200 HIV-1 RNA copies/mL or a drop of plasma viral load from baseline of more than 1 log10. A multivariate logistic regression analysis was performed to identify factors associated with virological response. RESULTS: The median age of the patients was 40 years, with a male to female ratio of 4:1. Fifty-one per cent of patients had received the three major classes of antiretrovirals and the median duration of previous antiretroviral therapy was 4.6 years. At baseline, the median plasma HIV RNA level was 4.4 log10 copies/mL and the median CD4 cell count was 274 cells/microL. At 3 months, 55% of patients (188 of 344) had a virological response, which was sustained at 6 months (53%). Predictors of virological response were exposure to two or fewer protease inhibitors [odds ratio (OR) 1.8; P=0.046], and use in optimized therapy of a new class of antiretrovirals (OR 2.9; P=0.006), of more than two new drugs (OR 3.0; P<0.0001), of abacavir (OR 1.9; P=0.03), or of lopinavir/ritonavir (OR 3.7; P=0.0002). CONCLUSIONS: A high proportion of patients achieved a short-term virological response in this cohort study. Patients with the least experience of protease inhibitor treatment and in whom a new class of antiretroviral, more than two new drugs, abacavir or lopinavir/ritonavir was used in optimized therapy had the best virological outcome. 相似文献
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Sigaloff KC Hamers RL Wallis CL Kityo C Siwale M Ive P Botes ME Mandaliya K Wellington M Osibogun A Stevens WS van Vugt M Rinke de Wit TF;PharmAccess African Studies to Evaluate Resistance 《The Journal of infectious diseases》2012,205(11):1739-1744
Little is known about the effect of human immunodeficiency virus type 1 (HIV-1) resistance mutations present at time of regimen switch on the response to second-line antiretroviral therapy in Africa. In adults who switched to boosted protease inhibitor-based regimens after first-line failure, HIV-RNA and genotypic resistance testing was performed at switch and after 12 months. Factors associated with treatment failure were assessed using logistic regression. Of 243 participants, 53% were predicted to receive partially active second-line regimens due to drug resistance. The risk of treatment failure was, however, not increased in these participants. In this African cohort, boosted protease inhibitors successfully resuppressed drug-resistant HIV after first-line failure. 相似文献
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The impacts of current antiretroviral therapy regimens on Chinese AIDS patients and their implications for HIV-1 drug resistance mutation 总被引:1,自引:0,他引:1
Zhang M Han XX Cui WG Jia MH Meng XD Xing AH Wu YH Yang YY Lu CM Hu QH Dai D Zhang ZN Shang H 《Japanese journal of infectious diseases》2008,61(5):361-365
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Sigaloff KC Ramatsebe T Viana R de Wit TF Wallis CL Stevens WS 《AIDS research and human retroviruses》2012,28(2):171-175
Patients failing antiretroviral treatment for extended periods of time are at risk of accumulating HIV drug resistance mutations (DRMs), which negatively influences second-line treatment. This retrospective study assessed the rate of DRM accumulation among South African patients with continued virological failure. Serial genotypic resistance testing was performed and DRMs were scored according to the 2009 IAS-USA list. Among 43 patients, 38 (88.4%) harbored ≥1 DRM. The median time between two sequential resistance tests was 5 months (IQR: 3-10). Thymidine analogue mutations accumulated at a rate of 0.07 mutation per month of drug exposure, which is faster than previously reported. Routine virological monitoring should be implemented in resource-limited settings to preserve susceptibility to second-line regimens. 相似文献
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Joep J.G. van Oosterhout Lillian Brown Ralf Weigel Johnstone J. Kumwenda Dalitso Mzinganjira Nasinuku Saukila Brian Mhango Thomas Hartung Sam Phiri Mina C. Hosseinipour 《Tropical medicine & international health : TM & IH》2009,14(8):856-861
Objectives In antiretroviral therapy (ART) scale-up programmes in sub-Saharan Africa viral load monitoring is not recommended. We wanted to study the impact of only using clinical and immunological monitoring on the diagnosis of virological ART failure under routine circumstances.
Methods Clinicians in two urban ART clinics in Malawi used clinical and immunological monitoring to identify adult patients for switching to second-line ART. If patients met clinical and/or immunological failure criteria of WHO guidelines and had a viral load <400 copies/ml there was misclassification of virological ART failure.
Results Between January 2006 and July 2007, we identified 155 patients with WHO criteria for immunological and/or clinical failure. Virological ART failure had been misclassified in 66 (43%) patients. Misclassification was significantly higher in patients meeting clinical failure criteria (57%) than in those with immunological criteria (30%). On multivariate analysis, misclassification was associated with being on ART <2 years [OR = 7.42 (2.63, 20.95)] and CD4 > 200 cells/μl [OR = 5.03 (2.05, 12.34)]. Active tuberculosis and Kaposi's sarcoma were the most common conditions causing misclassification of virological ART failure.
Conclusion Misclassification of virological ART failure occurs frequently using WHO clinical and immunological criteria of ART failure for poor settings. A viral load test confirming virological ART failure is therefore advised to avoid unnecessary switching to second-line regimens. 相似文献
Methods Clinicians in two urban ART clinics in Malawi used clinical and immunological monitoring to identify adult patients for switching to second-line ART. If patients met clinical and/or immunological failure criteria of WHO guidelines and had a viral load <400 copies/ml there was misclassification of virological ART failure.
Results Between January 2006 and July 2007, we identified 155 patients with WHO criteria for immunological and/or clinical failure. Virological ART failure had been misclassified in 66 (43%) patients. Misclassification was significantly higher in patients meeting clinical failure criteria (57%) than in those with immunological criteria (30%). On multivariate analysis, misclassification was associated with being on ART <2 years [OR = 7.42 (2.63, 20.95)] and CD4 > 200 cells/μl [OR = 5.03 (2.05, 12.34)]. Active tuberculosis and Kaposi's sarcoma were the most common conditions causing misclassification of virological ART failure.
Conclusion Misclassification of virological ART failure occurs frequently using WHO clinical and immunological criteria of ART failure for poor settings. A viral load test confirming virological ART failure is therefore advised to avoid unnecessary switching to second-line regimens. 相似文献
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Di Giambenedetto S Bacarelli A Pinnetti C Colafigli M Prosperi M Gatti G Cauda R De Luca A 《Scandinavian journal of infectious diseases》2007,39(9):813-818
The aim of this study was to establish the prevalence and predictors of genotypic resistance of HIV-1 to lopinavir and fosamprenavir from patients failing protease inhibitors (PI)-based regimens. We selected 643 HIV-1-infected patients with available treatment history who underwent genotypic resistance assays for virological failure from a clinical site and from the Stanford database. According to the genotypic resistance interpretation of the Stanford algorithm, proportions of viruses showing full susceptibility to fosamprenavir and lopinavir were 32% and 34%, respectively (p =ns). Proportions of viruses fully susceptible to lopinavir/r and fosamprenavir/r according to the Agence Nationale pour la Recherche sur le SIDA (ANRS) algorithm, were 81% and 81%, respectively. According to the Rega algorithm, proportions of viruses showing full susceptibility to fosamprenavir/r and lopinavir were 80% and 70%, respectively (p<0.001). According to the ANRS and Rega interpretations, the time on therapy predicted susceptibility to lopinavir/r, while susceptibility to fosamprenavir/r according to ANRS was predicted by the number of prior PI regimens experienced. According to the Stanford interpretation, prior indinavir exposure predicted resistance to lopinavir/r and fosamprenavir/r while prior nelfinavir use predicted susceptibility to both drugs. After failing PI-based regimens, the majority of viruses retained a predicted susceptibility to fosamprenavir/r and lopinavir/r. In patients failing PIs, the interpretation of genotypic resistance to fosamprenavir may change considerably according to the different algorithms and in respect to the effect of pharmacokinetic boosting with ritonavir. 相似文献
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