Human immunodeficiency virus development

Labrosse B, Morand-Joubert L, Goubard A, Rochas S, Labemardiere JL, Pacanowski J, Meynard JL, Hance AJ, Clavel E, Mammano E (2006) Role of the envelope genetic context in the development of enfuvirtide resistance in human immunodeficiency virus type 1-infected patients. J Virol 80 8807-8819... 

Whitcomb JM, Huang W, Fransen S, Limoli K, Toma J, Wiin T, Chappey C, Kiss LD, Paxinos EE, Petropoulos CJ (2007) Development and characterization of a novel single-cycle recombinant-virus assay to determine human immunodeficiency virus type 1 coreceptor tropism, Antimicrob Agents Chemother 51 566-575... 

In this chapter we describe the current insights into the evolution of viruses under pressure of antiviral therapy and the potential impact on viral fimess. As most recent work in this field has been done in the field of human immunodeficiency virus (HIV), we use the evolution of this virus as the basis for the chapter. Subsequently, we describe resistance evolution for Hepatitis B virus (HBV), where large progress has been made in recent years. Furthermore, we describe the resistance development for Hepatitis C virus (HCV), for which a very active drug development program is undertaken by several pharmaceutical companies. Finally, we discuss resistance evolution for Influenza. 

There is clear evidence linking defects of the immune system to the development of NMSC. For example, it is observed that patients receiving chronic immunosuppressant therapy for organ transplantation have a 50% risk of developing SCC within 20 years of transplantation, and 30% of these cancers are highly aggressive.21 Additionally, patients with human immunodeficiency virus (HIV) infection are predisposed to melanoma.18 Data also support the idea that UV radiation... 

HIV genotype A type of resistance testing for human immunodeficiency virus (HIV) in which a patient s blood sample is obtained, their HIV RNA is sequenced, and mutations that have developed that may confer resistance to antiretrovirals are reported. 

HIV phenotype A type of resistance testing for human immunodeficiency virus (HIV) in which a patient s blood sample is obtained, and the patient s HIV genes that encode for reverse transcriptase and protease are removed and placed in an HIV viral vector. This viral vector is replicated in a cell culture system with varying concentrations of antiretrovirals. A drug concentration-viral inhibition curve is developed and the concentration needed to inhibit 50% of the patient s virus is reported. This is used to predict resistance versus susceptibility. 

HIV virtual phenotype A database of matching human immunodeficiency virus (HIV) genotypes and phenotypes is developed. When an HIV genotype for a patient is obtained, the database is used to predict the patient s phenotype based on their actual genotype using matches that occur in the database. 

Kellam P, Boucher CAB, Larder BA. Fifth mutation in human immunodeficiency virus type 1 reverse transcriptase contributes to the development of high-level resistance to zidovudine. Proc Natl Acad Sci USA 1992 89 1934-1938. 

Neuropathy in human immunodeficiency virus infection has many causes. Multiple mechanisms cause neuropathy in patients with HIV. An immune-mediated, Guillain-Barre-like syndrome (see below) may occur at the time of HIV seroconversion. Later in the course of infection, patients may present with mononeuropathy multiplex, sometimes as a consequence of vasculitis associated with coinfection with hepatitis C. Distal sensory-autonomic axonal polyneuropathy may develop in patients with more advanced HIV, either as a consequence of high titers of HIV itself or of the neurotoxicity of antiretroviral drugs [18,19],... 

Human immunodeficiency virus (HIV) is the most important risk factor for active TB, especially among people 25 to 44 years of age. An HIV-infected individual with TB infection is over 100-fold more likely to develop active disease than an HIV-seronegative patient. 

In a biopsy of an AIDS patient s enlarged thymus (P4), the adipose involuted thymus, with persistence of many Hassall s corpuscles, was judged to be a large lymphoid follicular hyperplasia. This follicular hyperplasia was similar to that described for lymph nodes, spleen, and other lymphoid tissues at earlier stages of human immunodeficiency virus infection, before the development of acquired immune deficiency syndrome. Human immunodeficiency virus RNA and p 24 were detected in the hyperplastic germinal centers (lymphocytes and follicular dendritic infected cells) and also in many cells that may have been either lymphocytes or epithelial cells in the interfollicular areas. 

R. Zhang, R. B. Diasio, Z. Lu, T. Liu, Z. Jiang, W. M. Galbraith, S. Agrawal, Pharmacokinetics and Tissue Distribution in Rats of an Oligodeoxynucleotide Phosphorothi-oate (GEM 91) Developed as a Therapeutic Agent for Human Immunodeficiency Virus Type-1 , Biochem. Pharmacol. 1995, 49, 929 - 939. 

Dolin, R., Human studies in the development of human immunodeficiency virus vaccines, J. Infect. Dis., 172,1175-1183,1995. 

Leonard, S., Van Schepdael, A., Ivanyi, T., Lazar, L, Rosier, J., Vanstockem, M., Vermeersch, H., and Hoogmartens, J. (2005). Development of a capillary electrophoretic method for the separation of diastereoisomers of a new human immunodeficiency virus protease inhibitor. Electrophoresis 26, 627-632. 

Pharmacological research has also benefited from the development of sophisticated tools because they have made it possible for researchers to determine the exact molecular structure of compounds involved in the disease process. With this information, they can devise molecules that bond with and inactivate those compounds (just as enzymes bond with substrates). Consider just one example of this process the development of a drug to treat human immunodeficiency virus (HIV) infection. 

The rapid spread of acquired immune deficiency syndrome (AIDS) has prompted numerous efforts to develop therapeutic agents against the human immunodeficiency virus type 1 (HIV-1) [2351. Efforts have focused on inhibition of the virally encoded reverse transcriptase (RT) enzyme, which is responsible for the conversion of retroviral RNA to proviral DNA. The nucleoside RT inhibitors 3 -azidothymidine (AZT) and dideoxyinosine (ddl) have proven to be clinically useful anti HIV-1 agents [236], but due to their lack of selectivity versus other DNA polymerases, these compounds are flawed by their inherent toxi-... 

Blood is also regularly tested, not just for blood group compatibility, but also for infections carried in the blood such as human immunodeficiency virus (HIV) and hepatitis B and C viruses. Early in the AIDS epidemic, before the AIDS virus was identified and a test developed to detect whether a person has been exposed to the virus, patients did contract HIV through blood transfusions. Today, every unit of donated blood is tested for the presence of HIV, as well as for hepatitis B and C viruses. 

---