Human immunodeficiency virus progression

Human Immunodeficiency Virus. Human immunodeficiency vims (HIV) causes Acquired Immunodeficiency Syndrome (AIDS), which has no cure. HIV infects the cells of the human immune system, such as T-lymphocytes, monocytes, and macrophages. After a long period of latency and persistent infection, it results in the progressive decline of the immune system, and leads to full-blown AIDS, resulting in death. 

Ullum, H., Lepri, A. C., Victor, J., Aladdin, H., Phillips, A. N., Gerstoft, J., Skinhoj, P., and Pedersen, B. K. (1998). Production of beta-chemokines in human immunodeficiency virus (HIV) infection Evidence that high levels of macrophage in inflammatory protein-1-beta are asociated with a decreased risk of HIV progression. J. Infect. Dis. 177 331-336. 

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. 

Coinfection with human immunodeficiency virus (HIV) and tuberculosis accelerates the progression of both diseases, thus requiring rapid diagnosis and treatment of both diseases. 

The acquired immune deficiency syndrome (AIDS) was first recognized in 1981, and described in a cohort of young homosexual men with significant immune deficiency. Since then, human immunodeficiency virus type 1 (HIV-1) has been clearly identified as the major cause of AIDS.1 HIV-2 is much less prevalent than HIV-1, but also causes AIDS. HIV primarily targets CD4+ lymphocytes, which are critical to proper immune system function. If left untreated, patients experience a prolonged asymptomatic period followed by rapid, progressive immunodeficiency. Therefore, most complications experienced by patients with AIDS involve opportunistic infections and cancers. 

Coombs, R. W., et al. (1996). Association of plasma human immunodeficiency virus type-1 RNA level with risk of clinical progression in patients with advanced infection. J. Infect. Dis. 174,704-714. 

The progression of human immunodeficiency virus (HIV) towards its more advanced stages is accompanied by increasing body stores of iron. Iron accumulates in macrophages as well as microglia, endothelial cells and myocytes. The iron burden is especially intense in the bone marrow, brain white matter, muscle and liver. Such excesses of iron will enhance oxidative stress, impair several already compromised immune defence mechanisms and directly promote the growth of microbes (Boelaert et ah, 1996). 

Responses to live and killed vaccines generally are suboptimal for human immunodeficiency virus (HlV)-infected patients and decrease as the disease progresses. 

Nelfinavir is indicated for the treatment of human immunodeficiency virus (HIV) infection when antiretroviral therapy is warranted. At present, there are no results from controlled trials evaluating the effect of therapy with nelfinavir on clinical progression of HIV infection, such as survival or the incidence of opportunistic infections. 

Efavirenz (DMP 266) (1) is an effective non-nucleoside inhibitor of reverse transcriptase of the human immunodeficiency virus (HIV) recently registered by the US Food Drug Administration (FDA) for treatment of the acquired immunodeficiency syndrome (AIDS).1 2 3 Inhibition of HIV reverse transcriptase by nucleosides like azidothymidine (AZT) (2) is a proven therapy for delaying the progression to AIDS. However, the rapid viral mutation to resistant strains requires the development of new therapeutic agents. The recent development of both protease inhibitors and non-nucleoside reverse transcriptase inhibitors offers hope of effective treatment especially when coadministered. 

Hall CD, Dafni U, Simpson D, Clifford D, Wetherill PE, Cohen B, McArthur J, Hollander H, Yainnoutsos C, Major E, Millar L, Timpone J. Failure of cytarabine in progressive multifocal leukoencephalopathy associated with human immunodeficiency virus infection. N Engl J Med 1998 338 1345-51. 

Korin YD, Zack JA. 1998. Progression to the Gib phase of the cell cycle is required for completion of human immunodeficiency virus type 1 reverse transcription in T cells. J. Virol. 72 3161-68... 

Considerable selenium losses in wound exudates following severe burns have been recorded, and supplementation of a mixture of selenium, zinc, and copper leads to a reduction in respiratory infections." Supplementation, even in apparently selenium-adequate individuals, has some immune function stimulatory effects, including improvement in natural kfller cell activity and increases in IL-2 receptor expression." It has been speculated that the increased infection rates in acquired immunodeficiency syndrome (AIDS) patients may be related to selenium depletion and this may even influence the progression from human immunodeficiency virus (HIV) positivity to the AIDS syndrome. " ... 

Lefrere J> Roudot-Thoraval F, Morand-Joubert L, Petit J, Lerable J, Thauvin M> et al. Carriage of GB vims C/hepatitis G virus RNA is associated with a slower immunologic, vfrologic, and clinical progression of human immunodeficiency virus disease in coinfected individuals. J Infect Dis 1999 179 783-9. 

Martinez-Sierra C, Arizcorreta A, Diaz F, Roldan R, Martin-Herrera L, Perez-Guzman E, et al. Progression of chronic hepatitis C to liver fibrosis and cirrhosis in patients coinfected with hepatitis C virus and human immunodeficiency virus. Chn Infect Dis 2003 36 491-8. 

Coates RA, Farewell VT, Raboud J, Read SE, MacFadden DK, Calzavara LM, Johnson JK, Shepherd FA, Fanning MM (1990) Cofactors of progression to acquired immunodeficiency syndrome in a cohort of male sexual contacts of men with human immunodeficiency virus disease. Am J Epidemiol 132 717-722... 

Significant reductions in lymphocyte concentration (<1000/mm of blood) can be evident without apparent cause or in a variety of diseases, including acute inflammatory disorders, severe uremia, immune deficiency diseases such as systemic lupus erythematosus, chronic infections such as tuberculosis or human immunodeficiency virus (HIV) infection, malignancies, and connective tissue diseases. Lymphocytosis (>4000/mm ) may occur with mononucleosis, pertussis, measles, or chickenpox, and in lymphoid malignancies. A progressive increase in mature lymphocytes may be indicative of chronic lymphocytic leukemia. Increased levels of atypical lymphocytes may occur in patients with infections (e.g., mononucleosis, hepatitis, or cytomegalovirus), allergic reactions, or lymphomas." ... 

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