Evidence of stavudine-related phenotypic resistance among zidovudine- pretreated HIV-1-infected subjects receiving a therapeutic regimen of stavudine plus lamivudine [1]

Combination antiretroviral therapy including two-drug regimens demonstrated survival benefit and improvement of clinical outcome of HIV-1 infection in several controlled trials (1-3). The observed decline in morbidity and mortality due to AIDS appeared to be caused by the use of more aggressive antiretroviral treatments (4) including protease inhibitors (5-7). A therapeutic failure of triple-drug regimens could be due to either resistance to previously experienced reverse transcriptase inhibitors (8), protease inhibitors (9), or to both. Recently, two reports, one from France (the VIRADAPT study [10]) and another from the United States (GART [11]), provided evidence that antiretroviral therapy adapted to genotypic resistance mutations gave more effective results than therapy adapted to treatment history in patients who failed combination regimens. Our study was designed and performed after the publication of the 1996 International AIDS Society-USA (IAS-USA) guidelines for the treatment of HIV infection (12) when protease inhibitors were not yet available in Italy in clinical practice, to assess the feasibility of a two-drug treatment strategy for zidovudine-experienced patients. The aim was to verify in vivo the possibility of ZDV phenotypic susceptibility reemergence in patients treated with lamivudine to analyze virologic effects and changes in phenotypic and genotypic resistance pattern with two different two-drug combination regimens including zidovudine or stavudine plus lamivudine in zidovudine-experienced patients, and to evaluate the efficacy of two-drug regimens in AIDS-free nonnucleoside reverse transcriptase inhibitor-experienced patients.