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Abstract
Research and development of new antiretroviral agents are in great demand due to issues with safety and efficacy of the antiretroviral drugs. HIV reverse transcriptase (RT) is an important target for HIV treatment. RT inhibitors targeting early stages of the virus-host interaction are of great interest for researchers. There are a lot of clinical and biochemical data on relationships between the occurring of the single point mutations and their combinations in the pol gene of HIV and resistance of the particular variants of HIV to nucleoside and non-nucleoside reverse transcriptase inhibitors. The experimental data stored in the databases of HIV sequences can be used for development of methods that are able to predict HIV resistance based on amino acid or nucleotide sequences. The data on HIV sequences resistance can be further used for (1) development of new antiretroviral agents with high potential for HIV inhibition and elimination and (2) optimization of antiretroviral therapy. In our communication, we focus on the data on the RT sequences and HIV resistance, which are available on the Internet. The experimental methods, which are applied to produce the data on HIV-1 resistance, the known data on their concordance, are also discussed.
Highlights
Acquired HIV drug resistance is an essential problem of highly active antiretroviral therapy (HAART)
Genotypic assays are based on sequencing of nucleotide sequences of the HIV-1 genes with identification of patterns of HIV mutations associated with antiretroviral resistance
Genotypic assays cannot be used for modeling of the HIV-1 resistance based on nucleic acids since they do not provide any information about the relationship between the nucleic/amino acid sequences and the inhibitory activity of drugs against a specific variant of HIV-1
Summary
Acquired HIV drug resistance is an essential problem of highly active antiretroviral therapy (HAART). HIV reverse transcriptase (RT) is part of HAART and one of the most attractive targets for the HIV inhibition [1,2]. The antiretroviral drugs that inhibit HIV RT only allow decreasing the HIV-1 replication but do not provide the full elimination of the virus [3]. An acquired HIV RT resistance occurs due to the high rate of mutations in a particular region of the pol gene, encoding the HIV RT amino acid sequences [5]. There are a lot of data on the relationships between mutations and their combinations in the pol gene and the combination of medicines prescribed to a patient. There is information about activity of the nucleoside reverse transcriptase inhibitors (NRTI) and non-nucleoside reverse transcriptase inhibitors (NNRTI) approved by U.S Food and Drug
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