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  • Online Resource  (2)
  • SAGE Publications  (2)
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  • 1
    In: Antiviral Therapy, SAGE Publications, Vol. 10, No. 7 ( 2005-10), p. 779-790
    Abstract: Liver damage associated with hepatitis C (HCV) may influence the likelihood of experiencing discontinuation due to toxicities or patient/physician choice (TOXPC) in patients taking combination antiretroviral therapy (cART). Little information to address this concern is available from clinical trials as patients with HCV are often excluded. Aims To compare incidence rates of discontinuation due to TOXPC associated with specific antiretrovial drugs in patients with or without HCV. Patients/methods A total of 4929 patients from EuroSIDA under follow-up from January 1999 on a specific nucleoside pair (zidovudine/lamivudine, didanosine/stavudine, stavudine/lamivudine, or other) with a third drug (abacavir, nelfinavir, indinavir, nevirapine, efavirenz, lopinavir/ ritonavir or other boosted-protease inhibitor (PI)-containing regimen) and with known HCV serostatus were studied for the incidence of discontinuation of any nucleoside pair or third drug due to TOXPC. Incidence rate ratios were derived from Poisson regression models. Results In total 1358 patients had HCV (27.5%). During 12 799 person-years of follow-up there were 2141 discontinuations due to TOXPC for nucleoside pairs and 2501 for third drugs. The incidence of discontinuation due to TOXPC was consistently higher in patients with HCV after stratification by nucleoside pair or third drug. After adjustment for CD4 + count, gender, exposure group, time on HAART, region and treatment regimen, there were few differences in the rate of discontinuation due to TOXPC in those with HCV compared with those without for any nucleoside pairs or third drugs. Similar results were seen when concentrating on discontinuation due to toxicities alone. Conclusions Although patients with HCV generally had higher rates of discontinuation due to TOXPC compared with patients without HCV, there was little evidence to suggest that this was associated with any specific nucleoside pair or third drug used as part of cART. Our results do not suggest that any specific component of cART is more poorly tolerated in patients with HCV or that the presence of HCV should influence the choice between antiretrovirals used as part of a cART regimen.
    Type of Medium: Online Resource
    ISSN: 1359-6535 , 2040-2058
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2005
    detail.hit.zdb_id: 2118396-X
    SSG: 15,3
    Location Call Number Limitation Availability
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  • 2
    In: Antiviral Therapy, SAGE Publications, Vol. 10, No. 7 ( 2005-10), p. 791-802
    Abstract: Studies have suggested that HIV-1 may develop thymidine analogue mutations (TAMs) by one of two distinct pathways – the TAM1 pathway (including mutations 41L, 210W and 215Y) or the TAM2 pathway (including mutations 67N, 70R and 219E/Q) – under the pressure of a not fully suppressive thymidine-analogue-containing regimen. Methods Frozen plasma samples stored in the EuroSIDA repository were selected and sent to two central laboratories for genotypic analysis. We considered 733 patients with at least one genotypic test showing ≥1 TAMs (the first of these tests in chronological order was used). TAM1 and TAM2 genotypic profiles were defined in accordance with previous literature. Statistical modelling involved logistic regression and linear regression analysis for censored data. Results The observed frequencies of patterns classifiable as TAM1 or TAM2 profiles were markedly higher than the probabilities of falling into these classifications by chance alone. The chance of detecting a TAM2 profile increased by 25% per additional year of exposure to zidovudine. We found that mutations 67N and 184V were not associated with a particular TAM profile. In the presence of TAM2 profiles, the adjusted mean difference in the 6-month viral reduction was 0.96 log 10 copies/ml (95% confidence interval: 0.20; 1.73) higher in patients who started stavudine-containing regimens instead of zidovudine-containing regimens. Conclusions This study provides evidence that the suggested TAM clustering is a real phenomenon and that it may be driven by which thymidine analogue the patients has used. In patients with TAM2-resistant viruses, stavudine appears to retain greater viral activity than zidovudine.
    Type of Medium: Online Resource
    ISSN: 1359-6535 , 2040-2058
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2005
    detail.hit.zdb_id: 2118396-X
    SSG: 15,3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
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