Current Drug Targets - Infectious Disorders - Volume 3, Issue 4, 2003

HIV DRUG RESISTANCE AND APPROACHES TO NEW THERAPIES In the absence of preventative or therapeutic vaccines for the foreseeable future, antiretroviral therapy is the most effective weapon in the fight against HIV / AIDS. Currently, there are 19 drugs that are commercially available for the treatment of HIV-1 infection, including eight nucleoside analog inhibitors of reverse transcriptase (NRTI), three allosteric (non-nucleo Read More

The nucleoside reverse transcriptase inhibitors (NRTIs) were the first class of agents used for the treatment of HIV and remain an important component of combination antiretroviral therapy. Resistance to the NRTIs occurs by the acquisition of mutations in the reverse transcriptase gene that result in a structural change that either decreases the NRTI incorporation into the extending nucleotide chain or enhances removal Read More

Resistance-testing technology has been incorporated into the standard of care for human immunodeficiency virus type 1 (HIV-1) infection and therapy with protease and reverse transcriptase inhibitors. Inhibitors of HIV-1 entry represent an emerging mode of antiretroviral therapy, and HIV-1 entry inhibitors encompass three mechanistically distinct classes of agents known as attachment inhibitors, coreceptor inhibitors, and Read More

A global effort has been undertaken to control human immunodeficiency virus (HIV) though the development of vaccines and pharmacologics. Current FDA approved pharmacological inhibitors target two of the three viral enzymes critical to replication and maturation of infectious viral particles: reverse transcriptase (RT) and protease (Pr). Although combination therapies targeting RT and Pr have significantly reduced AI Read More

One of the most serious side effects associated with the therapy of HIV-1 infection is the appearance of viral strains that exhibit resistance to protease inhibitors. At the molecular level, resistance to protease inhibition predominantly takes the form of mutations within the protease molecule that preferentially lower the affinity of protease inhibitors with respect to protease substrates, while still maintaining a viable c Read More

We review some crucial aspects of drug therapy and viral resistance that have been investigated within the framework developed for the modelling of virus kinetics. First, we give a general overview on the use of mathematical models in the field of HIV research. We seek to identify the factors that determine the steady state virus load and show that stable reductions during antiviral therapy are difficult to explain within the stan Read More

There is currently an opportunity to carefully plan the implementation of antiretroviral (ARV) therapy in the developing world. Here, we use mathematical models to predict the potential impact that low to moderate usage rates of ARVs might have in developing countries. We use our models to predict the relationship between the specific usage rate of ARVs (in terms of the percentage of those infected with HIV who re Read More

The human immunodeficiency virus (HIV) exhibits extensive heterogeneity due to its rapid turnover, high mutation rate, and high frequency of recombination. Its remarkable genetic diversity plays a key role in virus adaptation, including development of drug resistance. The increasing complexity of antiretroviral regimens has favored selection of HIV variants harboring multiple drug resistance mutations. Evolution of dr Read More

The emergence of drug resistance remains a major problem during antiretroviral treatment of patients infected with human immunodeficiency virus type 1 (HIV-1). As phenotypic drug resistance is laborious and expensive to determine, and because numerous specific mutations are known to be correlated with different resistance patterns, genotyping of the reverse transcriptase and protease genes of HIV is fast becoming Read More

The development of resistance and the inability of currently approved antiretroviral drugs to completely eradicate HIV-1 have led to increased focus on therapies other than small molecules. Although nucleic acid-based intervention requires complex tasks involving intracellular delivery and / or stable expression in target cells, recent advances in gene therapy methods combined with continued progress in stem cell approache Read More