HIV-1 infection

The pathogenesis of AIDS (10,12,13) following HIV infection may be separated into primary and secondary effects. The primary effects are (/) quantitative and quahtative decreases in infected cells, ie, the T-lymphocytes (2) impaked cellular immunity (J) impaked immune surveillance and... 

Gradual diminution of 004 T-lymphocytes from the peripheral blood is the most consistent feature observed in HIV infection. Because the majority of 004 cells are T-helper lymphocytes, removal leads to deficiency of cellular immunity, which depends on T-helper cells to initiate cytotoxic T-ceU killing of vims-infected cells of cancer. The loss of immune surveillance leads to the appearance of viraHy induced tumors from unopposed clonal expansion of viraHy transformed cells. Furthermore, depletion of cellular immunity leads to exaggerated viral, fungal, and proto2oal infections. 

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. 

CarbocycHc 2/3 -didehydro-2/3 -dideoxyguanosine [118353-05-2] (carbovk, CBV, 66), C H 2N502, synthesized in 1988 (177), is a promising candidate for the chemotherapy of AIDS. CBV inhibits HIV repHcation and HIV-induced cytopathic effects in a variety of human T-lymphoblastoid ceU lines at concentrations approximately two hundred- to four hundredfold below its cytotoxic concentrations (177). CBV is as effective as AZT and DDC in reducing the expression of vkal antigen in HIV-infected CEM ceUs (177). The antivkal potency and selectivity of carbovk is comparable to the anti-HIV-1 potency and selectivity of 2/3 -dideoxyadenosine (178). The exact mode of antivkal action of carbovk has not yet been elucidated, but may be the modulating effect of intraceUular nucleotides on 5 -nucleotidase activity (179). 

An important notice to all gas fitters AIDS HIV infection and diving ... 

The most recent advance in treating HIV infections has been to simultaneously attack the virus on a second front using a protease inhibitor. Recall from Section 27.10 that proteases are enzymes that catalyze the hydrolysis of proteins at specific points. When HIV uses a cell s DNA to synthesize its own proteins, the initial product is a long polypeptide that contains several different proteins joined together. To be useful, the individual proteins must be separated from the aggregate by protease-catalyzed hydrolysis of peptide bonds. Protease inhibitors prevent this hydrolysis and, in combination with reverse transcriptase inhibitors, slow the reproduction of HIV. Dramatic reductions in the viral load in HIV-infected patients have been achieved with this approach. 

Nucleosides, nucleotides, peptidomimetics, and reverse transcriptase inhibitors in HIV infection therapy 98CCC449. 

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. 

However, several situations can be anticipated in which support of the immune system is required. These include congenital defects in the immune repertoire, acquired immune deficiencies such as in HIV infection, but also situations in which the immune system is compromised after treatment of patients, e.g., after radiation or chemotherapy. 

Several cytokines are in clinical use that support immune responses, such as IL-2, DFNs, or colony-stimulating factors. IL-2 supports the proliferation and effector ftmction of T-lymphocytes in immune compromised patients such as after prolonged dialysis or HIV infection. IFNs support antiviral responses or antitumoral activities of phagocytes, NK cells, and cytotoxic T-lymphocytes. Colony-stimulatory factors enforce the formation of mature blood cells from progenitor cells, e.g., after chemo- or radiotherapy (G-CSF to generate neutrophils, TPO to generate platelets, EPO to generate erythrocytes). 

Kaposi sarcoma (KS) - an angiogenic-inflammatory neoplasm - is the most prevalent cancer in HIV-infected patients and its appearance is preceded by infection with human Heipesvitus-8 (HHV-8). Although chemotherapy has become the treatment of choice approved by the FDA, there are also good response rates in patients treated with IFN-a. Fortunately, today highly active antiretroviral therapy (HAART) has dramatically decreased the incidence of KS in AIDS patients. 

Cysteine-cysteine chemokine receptor 5 (CCR5) A 32-bp deletion with a population frequency of about 0.1 in Caucasians results in truncated nonfunctional receptor. Carriers of this variant are partially protected from HIV infection, particularly the homozygous carriers. 

HSV2 (herpes simplex virus 2), which causes significant morbidity and is an important cofactor for the transmission of HIV infection was recently targeted in a mouse model by local application of siRNA mixed with lipids. The results suggested that siRNA could work as active components of microbicides to prevent viral infection or transmission [2]. 

Scherer L, Rossi JJ, Weinberg MS (2007) Progress and prospects RNA-based therapies for treatment of HIV infection. Gene Ther 14(14) 1057-1064... 

So far, five different protease inhibitors have been approved by the FDA for the treatment of HIV infection [3, 4]. Clinical trials in which protease inhibitors were evaluated in monotherapy demonstrated the potency of this class of inhibitors (decrease in HIV RNA levels, increase in CD4 cell counts). Treatment regimens were subsequently broadened to include reverse transcriptase inhibitors in combination with protease inhibitors. The result of these clinical trials has led to a list of guidelines with recommendations for the optimal treatment options. Prolonged control of the infection with combination therapy (highly active antiretroviral therapy, HAART ) could be shown. 

Saquinavir was the fust HIV protease inhibitor to obtain FDA approval in 1995 for the treatment of HIV infection... 

Patients receiving antiviral drugs for HIV infections may continue to develop opportunistic infectionsand other complications of HiV. The nurse monitors all patients closely for sgns of infection such as fever (even low-grade fever), malaise, sore throat, or lethargy. 

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