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Laura Monno, Amelia Appice, Rocco Cavaliere, Teresa Scarabaggio, Gioacchino Angarano, Highly Active Antiretroviral Therapy Failure and Protease and Reverse Transcriptase Human Immunodeficiency Virus Type 1 Gene Mutations, The Journal of Infectious Diseases, Volume 180, Issue 2, August 1999, Pages 568–570, https://doi.org/10.1086/314909
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To the Editor
To assess the role that genotypic mutations within the protease (PR) domain play in determining treatment failure, Young et al. [1] determined the sequence of PR and reverse transcriptase (RT) genes of human immunodeficiency virus type 1 (HIV-1) isolates from 35 patients in whom highly active antiretroviral therapy (HAART) was unsuccessful. Even though the authors found an unexpectedly low number of PR mutations (range, 0–6) and observed that failure may occur with only a few mutations, they emphasized the importance of patient drug exposure. Unquestionably, compliance and pharmacologic factors are important in determining the efficacy of any antiretroviral regimen, but they should not be considered the sole cause of treatment failure.
For this study, we selected 8 severely immunodeficient (median CD4+ cell count, 107) patients whose treatment had failed (as defined by a rise in plasma virus load or a decrease of <1 log10). The patients had received a combination regimen including a PR inhibitor, and their therapy was directly supervised by a responsible family member, leaving no doubt of treatment adherence. Most patients had received multiple nucleoside RT inhibitors for 124 months, either as monotherapy or as combination therapy, and at least two PR inhibitors (median duration, 11.5 months; range, 6–18). The sequences of plasmaderived PR- and RT-coding regions were determined with a 373 sequencer (Perkin-Elmer Cetus, Norwalk, CT) and compared by use of Factura software (BCM Search Launcher; Baylor College of Medicine, Houston) with the reference HXB2—HIV-1.
