HIV resistance

Treatment considerations for antiretroviral-experienced patients are much more complex than for patients who are naive to therapy. Prior to changing therapy, the reasons for treatment failure should be identified. A comprehensive review of the patient s severity of disease, antiretroviral treatment history, adherence to therapy, intolerance or toxicity, concomitant drug therapies, co-morbidities, and results of current and past HIV resistance testing should be performed. If patients fail therapy due to poor adherence, the underlying reasons must be determined and addressed prior to initiation of new therapy. Reasons for poor adherence include problems with medication access, active substance abuse, depression and/or denial of the disease, and a lack of education on the importance of 100%... 

De Clercq E. HIV resistance to reverse transcriptase inhibitors. Biochem Pharmacol 1994 47 155-169. 

Lipophilic peptide Multi-Nucleoside reverse transcriptase inhibitor conjugates synthesis to combat HIV resistance... 

HIV resistance may emerge in chronic hepatitis B patients with unrecognized or untreated HIV infection treated with antihepatitis B therapies, such as adefovir, that may have activity against HIV. 

Rowland-Jones, S. L., T. Dong, K. R. Fowke, J. Kimani, P. Krausa, H. Newell, T. Blanchard, K. Ariyoshi, J. Oyugi, E. Ngugi, J. Bwayo, K. S. MacDonald, A. J. McMichael, and F. A. Plummer. 1998. Cytotoxic T Cell Responses to Multiple Conserved HIV Epitopes in HIV-Resistant Prostitutes in Nairobi. Journal of Clinical Investigation 102 1758-1765. 

Galvani AP, Slatkin M. Evaluating plague and smallpox as historical selective pressures for the CCR5-Delta 32 HIV-resistance allele. Proc Natl Acad Sci USA 2003 100(25) 15276-15279. 

Biologists have now observed hundreds of cases of natural selection, beginning with the well-known examples of bacterial resistance to antibiotics, insect resistance to DDT and HIV resistance to antiviral dmgs. Natural selection accounts for the resistance of fish and mice to predators by making them more camouflaged, and for the adaptation of plants to toxic minerals in the soil.32... 

The CCR5A32 polymorphism, a 32-bp deletion in the receptor promoter, has been associated with protection against human immunodeficiency virus (HIV) infection, asthma, and other disease states [308-310]. While the potential contribution of the CCR5 variants to immune diseases is stronger in the case of HIV infection [311], it is not necessarily significant in genome-wide studies of HIV resistance ( Subheading 3.6.2). 

Zidovudine is a thymidine (a nucleoside) analogue and was the first drug introduced that inhibits reverse transcriptase. This action terminates the growing viral DNA strand. Because of HIV resistance, several similar drugs have been developed, including abacavir and lamivudine. 

Foscamet (4) is an inorganic pyrophosphate derivative that inhibits viral DNA, RNA polymerases and HIV reverse transcriptase (RT) directly without the need of any activation steps. It is in vitro active against HSV, VZV, CMV, EBV, HHV-6, HBV and HIV. Resistance is developed due to mutation in Ae DNA polymerase gene [13]. 

One example of this, the genotyping of HFV strains to predict drug resistance and thereby enable better chemotherapy, is reviewed in Blum, R.A., et al. HIV resistance testing in the USA—a model for the application of pharmacogenomics in the cUnical setting. Pharmacogenomics 2005, 6, 169-179. 

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