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  • SAGE Publications  (2)
  • Bedini, A  (2)
  • Conejero, J  (2)
  • 2000-2004  (2)
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  • SAGE Publications  (2)
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  • 2000-2004  (2)
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  • 1
    Online Resource
    Online Resource
    Response to Antiretroviral Therapy among Patients Exposed to Three Classes of Antiretrovirals: Results from the Eurosida Study
    SAGE Publications ; 2002
    In:  Antiviral Therapy Vol. 7, No. 1 ( 2002-01), p. 21-30
    Details
    In: Antiviral Therapy, SAGE Publications, Vol. 7, No. 1 ( 2002-01), p. 21-30
    Abstract: There is an increasing proportion of HIV-positive patients exposed to all licensed classes of antiretrovirals, and the response to salvage regimens may be poor. Among over 8500 patients in EuroSIDA, the proportion of treated patients exposed to nucleosides, protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitor (NNRTI) increased from 0% in 1996 to 47% in 2001. Four-hundred-and-thirteen patients, who had failed virologically two highly active antiretroviral therapy (HAART) regimens and experienced all three main drug classes, started a salvage regimen of at least three drugs, in which at least one new PI or NNRTI was included. Median viral load was 4.7 log copies/ml [Interquartile range (IQR) 4.2–5.2], CD4 lymphocyte count 150/mm 3 (IQR 60–274/mm 3 ) and follow-up 14 months. Of these patients, 283 (69%) subsequently experienced at least a 1 log decline in viral load and 202 (49%) achieved a viral load 〈 500 copies/ml. Conversely, the CD4 count halved from the baseline value in 88 (21%), and 45 (11%) experienced a new AIDS-defining disease. In multivariable analyses, a 1 log viral load reduction was related to baseline viral load [relative hazard (RH) 1.27 per 1 log higher; P=0.008], a previous viral load of less than 500 copies/ml (RH 1.69; P=0.002), more recent initiation of the regimen (RH 1.36 per year more recent; P=0.02), number of new drugs in the regimen (RH 1.20 per drug; P=0.02), time since start of antiretroviral therapy (RH 0.94 per extra year; P=0.035) and time spent on HAART with viral load 〉 1000 copies/ml (RH 0.96 per extra month; P=0.0001). Analysis of factors associated with CD4 count decline and new AIDS disease also indicated improved outcomes in more recent times and a tendency for a better response in those starting more new drugs, but no relationship with the total number of drugs. Outcomes in people starting salvage regimens appear to depend on the number of new drugs started but not on the total number of drugs being used.
    Type of Medium: Online Resource
    ISSN: 1359-6535 , 2040-2058
    URL: Article
    DOI: 10.1177/135965350200700103
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2002
    detail.hit.zdb_id: 2118396-X
    SSG: 15,3
    Location Call Number Limitation Availability
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    Online Resource
  • 2
    Online Resource
    Online Resource
    Baseline Resistance and Virological Outcome in Patients with Virological Failure who Start a Regimen Containing Abacavir: Eurosida Study
    SAGE Publications ; 2004
    In:  Antiviral Therapy Vol. 9, No. 5 ( 2004-07), p. 787-800
    Details
    In: Antiviral Therapy, SAGE Publications, Vol. 9, No. 5 ( 2004-07), p. 787-800
    Abstract: To investigate the ability of several HIV-1 drug-resistance interpretation systems, as well as the number of pre-specified combinations of abacavir-related mutations, to predict virological response to abacavir-containing regimens in antiretroviral therapy-experienced, abacavir-naive patients starting an abacavir-containing regimen in the EuroSIDA cohort. Patients and methods A total of 100 HIV-infected patients with viral load (VL) 〉 500 copies/ml who had a plasma sample available at the time of starting abacavir (baseline) were included. Resistance to abacavir was interpreted by using eight different commonly used systems that consisted of rules-based algorithms or tables of mutations. Correlation between baseline abacavir-resistance mutations and month 6 virological response was performed on this population using a multivariable linear regression model accounting for censored data. Results The baseline VL was 4.36 log 10 RNA copies/ml [interquartile range (IQR): 3.65–4.99 log 10 RNA copies/ml] and the median CD4 cell count was 210 cells/μl (IQR: 67–305 cells/μl). Our patients were pre-exposed to a median of seven antiretrovirals (2–12) before starting abacavir therapy. The median (range) number of abacavir mutations (according to the International AIDS Society-USA) detected at baseline was 3.5 (0–8). Overall, the Kaplan–Meier estimate of the median month 6 VL decline was 0.86 log 10 RNA copies/ml [95% confidence intervals (95% CI): 0.45–1.24]. The VL in those patients ( n=31) who intensified treatment by adding only abacavir decreased by a median 0.20 log 10 RNA copies/ml (95% CI: -0.18; +0.94). The proportion of patients who harboured viruses fully resistant to abacavir among the eight genotypic resistance interpretation algorithms ranged from 12% [Agence Nationale de Recherches sur le SIDA (ANRS)] to 79% [Stanford HIV RT and PR Sequence Database (HIVdb)] . Some interpretation systems showed statistically significant associations between the predicted resistance status and the virological response while others showed no consistent association. The number of active drugs in the regimen was associated with greater virological suppression (additional month 6 VL reduction per additional sensitive drug=0.51, 95% CI: 0.15–0.88, P=0.006); baseline VL was also weakly associated (additional month 6 VL reduction per log 10 higher=0.30, 95% CI: -0.02; +0.62, P=0.06). In contrast, the number of drugs previously received was associated with diminished viral reduction (additional month 6 VL reduction per additional drug=-0.14, 95% CI: -0.28; 0.00, P=0.05). Conclusions Our results revealed a high degree of variability among several genotypic resistance interpretation algorithms currently in use for abacavir. Therefore, the interpretation of genotypic resistance for predicting response to regimens containing abacavir remains a major challenge.
    Type of Medium: Online Resource
    ISSN: 1359-6535 , 2040-2058
    URL: Article
    DOI: 10.1177/135965350400900509
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2004
    detail.hit.zdb_id: 2118396-X
    SSG: 15,3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
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