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Benjamin Young, Daniel R. Kuritzkes, Reply, The Journal of Infectious Diseases, Volume 180, Issue 2, August 1999, Pages 570–571, https://doi.org/10.1086/314911
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Extract
To the Editor
Monno and colleagues [1] report the genetic sequences of human immunodeficiency virus type 1 (HIV-1) protease (PR) and reverse transcriptase (RT) from 8 patients for whom combination antiretroviral therapy failed [1]. Their results are qualitatively similar to ours [2]. We found that mutations in both the PR and RT genes of HIV-1 were common in a cohort of 35 patients for whom combination antiretroviral therapy that included a PR inhibitor had failed.
We attempted to emphasize in our report that, even though multiple mutations may be required for high-level phenotypic resistance to PR inhibitors in vitro [3, 4], failure of combination therapy was frequently associated with a small number of mutations in the PR gene. Thus, we are in agreement with Monno et al. [1], who state that a large number of mutations may not be necessary for PR inhibitor resistance. We agree also that resistance to RT inhibitors, particularly lamivudine and the nonnucleoside RT inhibitors, is an important factor in the failure of combination regimens, as demonstrated recently by several groups [5–7]. Although we suggested that problems with treatment adherence and pharmacologic factors might play a role in determining treatment outcome (particularly in patients for whom therapy failed without evidence of PR inhibitor resistance), we did not mean to imply that these factors were the sole causes of treatment failure.
