Abstract
Global AIDS epidemics caused by human immunodeficiency virus type 1 (HIV-1) has existed for more than 25 years and involved more than 2 million newly infected people annually. The obstacle in combating the global epidemics is a rapid evolution of the virus by the selection of drug resistance mutations. In this review, we have summarized scientific achievements in the field of reverse transcriptase drug resistance to licensed antiviral drugs--nucleoside (NRTI) and non-nucleoside (NNRTI) inhibitors. Principal mechanisms of their antiviral action, major drug resistance mutations, and molecular aspects of classic resistance mechanisms of HIV to NRTIs and NNRTIs are described. Recently discovered role of RNase H activity in development of drug resistance to reverse transcriptase inhibitors is a focus for the detailed discussion. New dual resistance mechanism to NRTIs and NNRTIs associated with the reverse transcriptase mutations in the C-terminal region, which includes RNase H and connection domains, is analyzed. Comprehensive analysis of the factors affecting the HIV drug resistance is important for the understanding molecular mechanisms of resistance for the improvement of drug design and anti-HIV therapy.
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