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Archived Comments for: Abacavir, efavirenz, didanosine, with or without hydroxyurea, in HIV-infected adults failing initial nucleoside/protease inhibitor-containing regimens

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  1. Lack of power for hydroxyurea comparison

    Christopher Gadd, NAM Publications Ltd.

    19 April 2005

    The paper by Swindells et al. provides some interesting information on the use of a combination of abacavir (Zerit), ddI (didanosine, Videx) and efavirenz (Sustiva) as second-line therapy for HIV infection after failure of an initial protease inhibitor-based regimen. This is particularly interesting, as the combination of abacavir and ddI is unusual. Although it includes no comparator group for this drug regimen, the study shows that this may be an acceptable treatment option for some patients.

    However, the main aim of the study seems to be to assess the additional effect of hydroxyurea on this combination's efficacy and safety. The investigators randomised the study participants to receive the drug or not, claiming in their abstract that their results show that "the addition of hydroxyurea blunted the CD4+ cell response, did not appear to enhance antiviral activity, and resulted in more treatment-limiting adverse events."

    This conclusion is unsupported by the data. The authors state, both in their Methods section and in the final sentence of their Discussion, that their study was not powered to detect a statistical difference between the hydroxyurea and no hydroxyurea arms - although the details of the power and sample size calculation are not given in the manuscript.

    Furthermore, the hydroxyurea group is sub-divided into an immediate and delayed treatment group. There is no information given on whether or how the separate results from these two sub-groups were combined in their final analysis.

    Given the authors' own admission of the small sample size in the study and the lack of power, it is misleading to state that their results show evidence of an effect of hydroxyurea on CD4 cell count responses and adverse events, nor that they show no evidence of alterations in this drug combination's antiviral activity.

    The true situation is that their study, taken alone, does not provide any interpretable information on the effects of hydroxyurea on this drug regimen. Nevertheless, the future inclusion of this data in systematic reviews may add to the weight of evidence from other similar trials.

    Competing interests