Viruses opportunistic infections

In advanced AIDS, MM is usually associated with opportunistic infections such as CMV (Said et al. 1991 RouUet et al. 1994 Kolson and Gonzalez-Scarano 2001) or is secondary to lymphoma (Fuller et al. 1993). Despite a role for other herpes viruses in AIDS-associated myelitis, no substantive evidence has been published in support of a role for other vimses in the development of HIV-associated MM, including herpes simplex 1 or 2, varicella zoster, or Epstein Barr vims (Kolson and Gonzalez-Scarano 2001). MM can occur secondary to hepatitis B and C viruses, which are common co-infections of HIV-infected patients, particularly when there is an associated cryoglobulinemia (Taillan et al. 1993 Caniatti et al. 1996). Rarely... 

Marr KA, Boeckh M, Carter RA, et al. Combination antifungal therapy for invasive aspergillosis. Clin Infect Dis 2004 39 797-802. Masur H, Kaplan JE, Holmes KK, et al. 1999 USPHS/IDSA guidelines for the prevention of opportunistic infections in persons infected with human immunodeficiency virus. Clin Infect Dis 2000 30 S29-S65. 

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. 

Immunocompromised A condition in which the immune system is not functioning normally. This condition is seen in the very young, the very old, human immunodeficiency virus-infected individuals, and in transplant patients. An immunocompromised person is susceptible to opportunistic infections. 

Acquired Immunodeficiency Syndrome (AIDS) A clinical syndrome due to infection with the RNA human immunodeficiency (retro)virus (HIV) which produces severe immunosuppression (depletion of natural killer T cells), thereby exposing the individual to a variety of opportunistic infections and cancers. 

Considerable data is available suggesting thatmild-to-moderate immunosuppression can lead to an increase in infectious disease. The types of infections that occur tend to result from either common pathogens (e.g., causing upper respiratory tract infections) or latent viruses (e.g., herpes cold sores), rather than opportunistic organisms such as Pnuemocyctis carinii. These are usually not life-threatening, except in certain susceptible populations, such as the elderly. Opportunistic infections, in contrast, are more prevalent in individuals where severe forms of immunosuppression are present, such as primary immunodeficiency diseases or HIV/AIDS. 

The concentrations of nitrite or nitrate in the sera of patients infected with H IV-1 are substantially raised, especially in those with low CD4 cell counts [118]. However, during HIV-1 infection, it is difficult to find out whether the NO production is attributable to virus replication or to opportunistic infections, or both. In vitro there is a substantial rise in nitrite concentrations from blood mononuclear cells and polymorphonuclear leucocytes from patients with AIDS, especially in those with neurological disorders and pulmonary disease caused by intracellular opportunistic pathogens [121]. Interestingly, the serum concentrations of nitrate are positively correlated with plasma and cell-associated viral loads, which suggests that HIV-1 may induce NO synthesis in vivo [119]. However, the results clearly show that there is a close relation between viral replication and iNOS expression or peaks of plasma nitrate in the absence of any opportunistic infections, in either in macaques or infected patients [119, 122, 123]. 

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. 

Kaplan, J.E., Hanson, D., Dworkin, M.S., Frederick, T., Bertolli, J., Lindegren, M.L., Holmberg, S. and Jones, J.L. (2000) Epidemiology of human immunodeficiency virus-associated opportunistic infections in the United States in the era of highly active antiretroviral therapy. Clinical Infectious Diseases, 30, S5—S14. 

The acquired immune deficiency syndrome (AIDS) has become a serious public health problem around the world, and commands much concern in medical and lay circles alike. Its causative agent is a human T-cell lymphotropic virus (HIV) that destroys helper/inducer T cells (discussed in chapter 6) of the immune system and causes mortality by allowing opportunistic infections and malignancies. A compound designed along traditional lines, 3 -azido-3 -deoxythymidine (9.16, AZT), emerged as one of the first useful therapeutics. However, since that time many other drugs have been devised. 

AIDS represents the classic example of immunodeficiency disease caused by extrinsic factors, in this instance the human immunodeficiency virus (HIV). This virus exhibits a strong tropism for CD4 T helper cells these become depleted, giving rise to increased frequency of opportunistic infections and malignancies in infected individuals. AIDS is also characterized by an imbalance in THl and TH2 cells, and the ratios of cells and their functions are skewed toward TH2. This results in hypergammaglobulinemia, loss of cytotoxic lymphocyte activity, and delayed hypersensitivity. 

Pneumocystis carini pneumonia (PCP), the most common of the opportunistic infections, occurs in more than 80% of AIDS patients (13). Toxoplasmosis, a protozoan infection of the central nervous system, is activated in AIDS patients when the CD4+ count drops and severe impairment of cell-mediated immunity occurs. Typically, patients have a mass lesion(s) in the brain. These mass lesions usually respond well to therapy and can disappear completely. Fungal infections, such as Cyptococcalmeningitis, are extremely common in AIDS patients, and Histoplasma capsulatum appears when cell-mediated immunity has been destroyed by the HIV virus, leading to widespread infection of the lungs, liver, spleen, lymph nodes, and bone marrow. AIDS patients are particularly susceptible to bacteremia caused by nontyphoidal strains of Salmonella. Bacteremia may be cleared by using antibiotic therapy. 

Antiviral agents (qv) (15—17) are used in attempts to combat the devastating effect of HIV on the immune system. As of this writing there are three principal approaches to the treatment of AIDS (/) use of anti-HIV agents to destroy the virus or control its growth the National Cancer Institute (NCI) encourages submission of synthetic and characterized natural products for anti-HIV screening (18) (2) immunotherapy to restore impaired immune functions and (3) treatment of specific opportunistic infections or tumors. 

According to the CDC, the diagnosis of AIDS constitutes certain opportunistic infections, neoplasms, encephalopathy or wasting syndrome in the presence of HIV infection. In 1993, the CDC expanded the criteria to also include CD4+ T-cell count below 200 cells/p,l in the presence of HIV infection. The most common opportunistic infections includepneumocystis carinii pneumonia, pneumonitis, toxoplasmosis, mycobacterial disease, recurrent herpes simplex virus infection and/or cytomegalovirus infection. Kaposi s sarcoma is the most common form of cancer. HIV-related nervous system diseases include acute septic meningitis, AIDS dementia complex, subacute encephalitis, HIV encephalopathy and CNS opportunistic infections and neoplasm. 

The treatment of patients with AIDS and individuals infected by HIV is continually being modified as new drugs become available and more information is gained about the nature of the AIDS virus. Currently, the pharmacologic management of HIV-infected patients consists of two principal strategies (1) controlling the proliferation and effects of HIV in individuals infected with this virus and (2) treatment and prevention of various opportunistic infections that... 

Hung CC, Chang SC. Impact of highly active antiretroviral therapy on incidence and management of human immunodeficiency virus-related opportunistic infections. J Antimicrob Chemother. 2004 54 849-853. 

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