AIDS related complex

Another dideoxypyrimidine nucleoside active against human immunodeficiency vims is 3 -azido-2/3 -dideoxyuridine [84472-85-5] (AZDU or CS-87, 64) C H N O. Since its synthesis, (167) CS-87 has been identified as a promising antiHIV agent (168) and is currentiy undergoing phase I clinical trials in patients with AIDS and AIDS-related complex. It appears to be less potent than AZT against HIV in a peripheral blood mononuclear (PBM) cell screening system and in MT-4 cell lines. This lower activity in PBM cells appears to be related to a lower affinity of CS-87 for the enzyme responsible for its initial phosphorylation (169). However, CS-87 has significantly lower toxicity on bone marrow cells than AZT (170) and penetration of the CNS as a 5 -dihydropyridine derivative. 

Cornblath DR, Hoke A (2006) Recent advances in HIV neuropathy. Curr Opin Neurol 19(5) 446-450 Cornblath DR, McArthur JC (1988) Predominantly sensory neuropathy in patients with AIDS and AIDS-related complex. Neurology 38(5) 794-796 Cornblath DR, McArthur JC et al (1987) Inflammatory demyeUnating peripheral neuropathies associated with human T-cell lymphotropic virus type III infection. Ann Neurol 21(l) 32-40 Corral I, Quereda C et al (1997) Acute poly radiculopathies in HIV-infected patients. J Neurol 244(8) 499-504... 

ABG Arterial blood gases ARC AIDS-related complex... 

Pialoux G, Youle M, Dupont B, Gazzard B, Cauwenbergh GFMJ, Stoffels PAM, Davies S, De Saint Martin J, Janssen PAJ. Pharmacokinetics of R82913 in patients with AIDS or AIDS-related complex. Lancet 1991 338 140-143. 

Severe, and in particular chronic, infection can also sometimes induce anaemia, which is often made worse by drugs used to combat the infection. For example, anaemia is evident in 8 per cent of patients with asymptomatic HIV infection. This incidence increases to 20 per cent for those with AIDS-related complex, and is greater than 60 per cent for patients who have developed Kaposi s sarcoma. Up to a third of AIDS patients treated with zidovudine also develop anaemia. Again, several trials have confirmed that EPO treatment of AIDS sufferers (be they receiving zidovudine or not) can increase haematocrit values and decrease transfusion requirements. 

After this initial phase of infection subsides, the free viral load in the blood declines, often to almost undetectable levels. This latent phase may last for anything up to 10 years or more. During this phase, however, there does seem to be continuous synthesis and destruction of viral particles. This is accompanied by a high turnover rate of (CD4+) T-helper lymphocytes. The levels of these T-lymphocytes decline with time, as does antibody levels specific for viral proteins. The circulating viral load often increases as a result, and the depletion of T-helper cells compromises general immune function. As the immune system fails, classical symptoms of AIDS-related complex (ARC) and, finally, full-blown AIDS begin to develop. 

The role of zinc(II) in clinical responses is complex and inconsistent. Nevertheless the idea that Zn(II) supplementation might improve the immunodeficiency in AIDS patients has prompted clinical trials of Zn(II) in humans. The results have been controversial in one study no significant effect of zinc gluconate in patients with AIDS-related complex was observed (383), while in another study (384), the administration of Zn(II) showed promising effects. At neutral pH, Zn(II) is an effective inhibitor of HIV protease (385). 

HIV is present in peripheral blood mononuclear cells, the major source of transmitted virus. Titers, however, are quite low, about 10,000 infectious doses per ml of blood, so that the blood is less infectious than in hepatitis B virus infections. The amount present tends to fall after seroconversion and rises again during development of AIDS-related complex and AIDS. Smaller amounts of virus are also present in semen and saliva, and probably even smaller amounts in colostrum, the human cervix, and tears. Infection is reported in CD4 positive submucosal cells in the rectum and large bowel and could be a route of entry in homosexuals. 

However, selective HR2 antagonists have attracted interest because of their potential immune response-modifying activify [88]. Mosf data suggest that cimetidine has a stimulatory effect on the immune system, possibly by blocking the receptors on subsets of T lymphocytes and inhibiting HR2-induced immunosuppression. Cimetidine has also been used successfully to restore immune functions in patients with malignant disorders, hypogammaglobulinemia and AIDS-related complexes. 

Fernandez F, Adams F, Levy JK, et al Cognitive impairment due to AIDS-related complex and its response to psychostimulants. Psychosomatics... 

Holmes VF, Fernandez F, Levy JK Psychostimulant response in AIDS-related complex patients. J Clin Psychiatry 50 5-8, 1989... 

Batki SL. Buspirone in drug users with AIDS or AIDS related complex. J Clin Psychopharmacoi 1990 10[Suppl 3] 1115-1155. 

Note AIDS is caused by HIV, which impairs both cellular and humoral immune functions, and this results in increased susceptibility to opportunistic infection and certain malignancies. The medical aspects of HIV infection include AIDS-related complex (weight loss, chronic diarrhea, fever, thrush, herpes zoster, fatigue), opportunistic infections and cancer, end-stage renal disease, blindness (cytomegalovirus), HIV encephalopathy, and dementia. The psychological aspects of HIV infection include major depression, regression, and suicidal impulses, delirium, substance abuse, antisocial personality, and bereavement. 

Adachi, M., Hayami, M., Kashiwagi, N., et al. (1988) Expression of LeY antigen in human immunodeficiency virus-infected human T cell lines and in peripheral lymphocytes of patients with acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC). J. Exp. Med. 167(2), 323-331. 

Tersmette, M., de Goede, R. E., Al, B. J., Winkel, I. N., Gruters, R. A., Cuypers, H. T., et al. (1988) Differential syncytium-inducing capacity of human immunodeficiency virus isolates frequent detection of syncytium-inducing isolates in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex. J. Virol. 62, 2026-2032. 

Uses. Zidovudine is indicated for serious manifestations of HIV infection in patients with acquired immunodeficiency s5mdrome (AIDS) or AIDS-related complex, i.e. those with opportunistic infection, constitutional or neurological symptoms, or with low CD4 counts treatment reduces the frequency of opportunistic infections and prolongs survival when used in effective combinations. It is also indicated alone for pregnant women and their offspring for prevention of maternal-fetal HIV transmission. 

Pai, S.M. Shukla, U.A. Grasela, T.H. Knupp, C.A. Dolin, R. Valentine, F.T. McLaren, C. Liebman, H.A. Martin, R.R. Pittman, K.A. Barbhaiya, R.H. Population pharmacokinetic analysis of didanosine (2, 3 -dideoxyino-sine) plasma concentration obtained in phase I clinical trials in patients with AIDS or AIDS-related complex. J. Clin. Pharmacol. Ther. 1995, 52, 164—169. 

Yarchoan R, Mitsuya H, Pluda JM, Marczyk KS, Thomas RV, Hartman NR, Brouwers P, Perno CF, AUain JP, Johns DG, et al The National Cancer Institute phase I study of 2, 3 -dideoxyinosine administration in adults with AIDS or AIDS-related complex analysis of activity and toxicity profiles. Rev Infect Dis 1990 12(Suppl 5) S522-33. 

Lambert JS, SeidUn M, Reichman RC, Plank CS, Laverty M, Morse GD, Knupp C, McLaren C, PettineUi C, Valentine FT, et al 2, 3 -dideoxyinosine (ddl) in patients with the acquired immunodeficiency syndrome or AIDS-related complex. A phase I trial. N Engl J Med 1990 322(19) 1333-40. 

Broder S, Yarchoan R, Collins JM, Lane HC, Markham PD, Klecker RW, Redfield RR, Mitsuya H, Hoth DF, Gelmann E, et al. Effects of suramin on HTLV-IIFLAV infection presenting as Kaposi s sarcoma or AIDS-related complex clinical pharmacology and suppression of virus replication in vivo. Lancet 1985 2(8456) 627-30. 

Connolly KJ, Allan JD, Fitch H, Jackson-Pope L, McLaren C, Canetta R, Groopman JE. Phase I study of 2 -3 -dideoxyinosine administered orally twice daily to patients with AIDS and AIDS-related complex and hematologic intolerance to zidovudine. Am JMed 1991 91 471-478. 

Yarchoan R, Pluda JM,Thomas RV, Mitsuya H, Brouwers P,Wyvill KM, Hartman N, Johns DG, Broder S. Long-term toxicity/activity profile of 2, 3 -dideoxyinosine in AIDS or AIDS-related complex. Lancet 1990 336 526-529. 

Infection by the virus produces antibodies, but not all of those exposed develop chronic infection. For those that do, AIDS or AIDS-related complex (ARC) bring on a variety of ailments involving the lymph nodes, intermittent fever, loss of weight, diarrhea, fatigue, pneumonia, and tumors. A person infected, known as HIV-positive, can remain disease-free for up to 10 years, as the virus can remain dormant before full-blown AIDS develops. 

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