Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Zalcitabine is an analogue of the nucleoside deoxycytidine which, when intracellularly converted to an active triphosphate metabolite, inhibits replication of human immunodeficiency virus (HIV). Zalcitabine is thought to act in the early phase of HIV replication by inhibiting reverse transcriptase and terminating the viral DNA chain. In vitro, zalcitabine is one of the more effective nucleoside analogues currently in clinical use for HIV infection, with 0.5 mumol/L concentrations completely inhibiting HIV replication in human T lymphocyte cell lines. In clinical trials, p24 antigen levels decreased and CD4 cell counts increased in patients with acquired immunodeficiency syndrome (AIDS) receiving zalcitabine > or = 0.03 mg/kg/day as monotherapy. Dose-dependent adverse effects that include peripheral neuropathy, stomatitis and rash, restrict long term use at higher dosages, and it is unclear whether zalcitabine monotherapy is as effective as zidovudine in extending survival in HIV-infected patients. Alternating or concomitant therapy with zalcitabine and zidovudine provides effective inhibition of viral replication and disease progression (as measured by improvements in CD4 cell counts) with lower and less toxic dosage regimens. At present, therefore, zalcitabine has a place in AIDS therapy both in combination with zidovudine, and as monotherapy for patients unable to tolerate zidovudine.
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PMID:Zalcitabine. A review of its pharmacology and clinical potential in acquired immunodeficiency syndrome (AIDS). 128 Oct 77

In the 1990s, HIV has replaced syphilis as the "great masquerader." Virtually every level of the neuraxis may be affected in a patient with HIV infection. The superimposition of multiple levels of neuropathology further complicate the bedside neurologic diagnosis of an AIDS patient. This article has reviewed the variety of forms of peripheral neuropathy that may be associated with HIV infection and its treatment. Distal symmetrical polyneuropathy may be produced in patients with HIV infection by neurotoxic drugs (e.g., vincristine, INH, ddC, or ddI) or by vitamin B12 deficiency or may develop in the later stages of HIV infection without identifiable cause. GBS and CIDP occur with increased frequency in early HIV infection owing to presumed autoimmunity, and these IDPs respond to plasmapheresis or prednisone, similar to HIV-seronegative patients. A limited distribution of mononeuropathy simplex or multiplex occurs in patients with CD4 counts greater than 200; the neuropathy will usually spontaneously improve in these patients. Widespread mononeuropathy multiplex may occur in patients with AIDS and CD4 counts less than 50 and is then usually caused by CMV infections; those neuropathies are usually progressive unless antiviral treatment is given. Progressive polyradiculopathy usually occurs in patients with AIDS and low CD4 counts. If the cerebrospinal fluid has a polymorphonuclear pleocytosis, CMV infection is almost always present, and progression is expected unless ganciclovir therapy is promptly started. Finally, mild autonomic neuropathy is commonly present in HIV-infected patients. Protocols for the evaluation and therapy of cranial and peripheral neuropathies are presented (Figs. 6 and 7). It is unfortunate but likely that increasing numbers of "neuro-AIDS" patients will be encountered, not only in urban medical centers but also in general community practice. The pace at which research in the field of HIV research has proceeded is unprecedented. It is, therefore, important that neurologists stay at the forefront of investigation and clinical care of these complex disorders.
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PMID:Peripheral neuropathies associated with human immunodeficiency virus infection. 132 49

Patients with acquired immunodeficiency syndrome frequently suffer peripheral neuropathy. We investigated its prevalence and relationship to clinical stage of human immunodeficiency virus (HIV) infection using quantitative sensory testing and nerve conduction testing. Vibratory threshold was determined in the right great toe and index finger of 179 men seropositive for HIV (28 with acquired immunodeficiency syndrome [AIDS] or AIDS-related complex [ARC], 151 asymptomatic) and 32 HIV-seronegative controls. None had clinical peripheral neuropathy. Abnormal threshold was control mean plus 2.5 SDs. In the toe, 10 (36%) of 28 subjects with AIDS or ARC had abnormal vibratory thresholds, compared with seven (5%) of 151 asymptomatic seropositive subjects and none of 32 controls. A subgroup of 168 seropositive subjects underwent nerve conduction testing. Abnormality rates were similar, but abnormalities of nerve conduction coincided with quantitative sensory testing abnormalities in only half the cases. Mean (+/-SD) vibratory threshold was significantly greater in subjects with AIDS or ARC (3.00 +/- 0.51 vibratory units) than in asymptomatic subjects (1.56 +/- 0.27 vibratory units) and controls (1.63 +/- 0.54 vibratory units). Finger abnormality rates did not differ, although subjects with AIDS or ARC had greater mean vibratory threshold. Subclinical peripheral neuropathy is thus related to stage of HIV infection and is present by quantitative sensory testing in 36% of patients with AIDS or ARC.
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PMID:Sensory testing in human immunodeficiency virus type 1-infected men. HIV Neurobehavioral Research Center Group. 136 Feb 2

Didanosine is a dideoxynucleoside analogue which undergoes intracellular conversion to the putative active triphosphate metabolite. The active metabolite appears to inhibit viral reverse transcriptase and terminate the proviral DNA, and produces virustatic inhibition of actively replicating human immunodeficiency virus (HIV) at clinically relevant concentrations. In phase I studies didanosine had beneficial effects on various surrogate markers of clinical efficacy and also improved clinical manifestations of HIV infection, with a 21-month survival rate of 80% in patients with acquired immune deficiency syndrome (AIDS) and 93% in patients with AIDS-related complex (ARC) in 1 study. Didanosine also improved CD4+ cell counts in a phase II/III trial in patients previously treated with zidovudine, whereas cell counts declined in patients continuing zidovudine therapy. However, the effects of didanosine on clinical end-points (disease progression, survival, HIV encephalopathy) remain to be established. Peripheral neuropathy and pancreatitis are the predominant dose-limiting adverse events and didanosine therapy should be withdrawn in patients developing signs or symptoms of pancreatitis and during acute treatment of Pneumocystis carinii pneumonia. However, at currently recommended clinical dosages didanosine is generally well tolerated with minimal haematological toxicity. Thus, in a therapeutic area with few treatment options, didanosine offers a welcome alternative for patients intolerant of, or resistant to, zidovudine. There are a number of clinical trials in progress evaluating didanosine alone or in combination with other antiviral agents, and these results are awaited with considerable interest.
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PMID:Didanosine. A review of its antiviral activity, pharmacokinetic properties and therapeutic potential in human immunodeficiency virus infection. 137 14

Great strides have been made in the therapy of human immunodeficiency virus (HIV) infection. Currently approved drugs include zidovudine and didanosine. A third drug, dideoxycytidine (zalcitibine), has recently been filed for approval with the Food and Drug Administration. All these drugs work through inhibition of the reverse transcriptase enzyme. Zidovudine is the only drug that has shown clinical efficacy against HIV. Treatment of patients with advanced HIV disease (i.e., acquired immune deficiency syndrome [AIDS] or symptomatic infection with < 200 CD4+ lymphocytes per mm3), results in a prolongation and improved quality of life. Zidovudine is the only antiretroviral agent approved for the treatment of asymptomatic patients. Early intervention with zidovudine has been shown to delay progression to AIDS when patients' CD4+ lymphocyte counts decline to less than 500/mm3, irrespective of clinical signs or symptoms of HIV infection. Didanosine is currently indicated for the treatment of patients with advanced HIV disease who are intolerant to or failing zidovudine therapy. The major toxicity of zidovudine is bone marrow suppression with anemia and granulocytopenia (which occurs in from 1% to 45% of patients, depending on the clinical stage of disease and the dose of the drug). Didanosine and zalcitibine have both been associated with a severe peripheral neuropathy, which is generally reversible on cessation of the drug. In addition, didanosine has been implicated as a cause of pancreatitis that has been fatal in a small percentage of cases. The toxicities of didanosine and zalcitibine range from 1% to 10%, depending on dose, duration of therapy, and the presence of underlying HIV-related peripheral neuropathy or a previous history of pancreatitis. The clinical hallmark of HIV infection is the development of opportunistic infections and malignancies, which are a consequence of the profound immunodeficiency. The risk of an opportunistic infection increases significantly as the T-helper lymphocyte count declines to less than 20%, or 200 to 250/mm3. The spectrum of opportunistic infections ranges from viruses to protozoa. Patients with advanced HIV disease are also at increased risk of infection with nonopportunistic, community-acquired pathogens. Primary and secondary prophylaxis against the most common AIDS-defining opportunistic infection, Pneumocystis carinii pneumonia, is now recommended. Studies are currently underway to determine the efficacy of prophylaxis against other opportunistic pathogens. Treatment of opportunistic infections associated with AIDS has improved significantly over the past 5 years as new drugs and combination regimens of antimicrobials have been developed.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:AIDS: Part II. 139 36

In this article the literature about didanosine, an antiretroviral drug, is reviewed. The mechanism of action, biochemical pharmacology, pharmacokinetics, and clinical results of phase-I trials are discussed. Serious adverse effects such as pancreatitis and peripheral neuropathy have occurred in these trials. An antiretroviral effect was observed in terms of an increase in CD4+ lymphocytes and a decrease in p24 antigen levels in HIV-infected individuals. Didanosine seems to be a promising drug against HIV infection, but knowledge about its clinical efficacy is scanty.
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PMID:Didanosine, a new antiretroviral drug. A review. 143 13

There have been reports in the medical community of hesitation regarding the administration of didanosine to adult HIV patients because of the fear of the documented toxicities associated with didanosine. The most worrisome toxicities include pancreatitis and peripheral neuropathy. With close observation and follow-up, these toxicities can almost always be avoided or easily reversed. This article attempts to allay these fears so that the practitioner can administer this effective antiretroviral confidently and safely. The development of nucleoside and the pharmacology of didanosine are discussed. Drug administration information is provided, including a description of the different forms of didanosine currently available. Guidelines for assessing toxicities associated with didanosine, as well as suggestions for patient education, are also provided. Data gathered at the National Cancer Institute in the phase I didanosine trial indicate that early detection and discontinuation of didanosine, in nearly all cases, can limit or lessen the extent of morbidity.
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PMID:Didanosine use in the adult HIV patient. 146 32

Myelosuppression is associated with human immunodeficiency virus (HIV) infection and may also be produced by agents used for the treatment of the disease or the treatment of its complications. Didanosine (ddl; 2',3'-dideoxyinosine) is a newer purine nucleoside that has recently become available for therapy for HIV infection. The effects of didanosine on peripheral blood counts have been retrospectively evaluated in the first 170 patients treated with this new agent in four phase I trials. Patients treated with didanosine showed statistically significant improvements in hemoglobin levels, white cell counts, and granulocyte and platelet numbers as compared with baseline values. These changes were seen with or without prior therapy with zidovudine, were somewhat more pronounced at higher doses of didanosine, and persisted for up to 1 year. Reported adverse events included peripheral neuropathy, diarrhea, and most notably, pancreatitis. It is concluded that, while some toxic side effects occur, didanosine therapy in HIV infection is associated with an amelioration of HIV-induced myelosuppression.
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PMID:Effects of therapy with didanosine on hematologic parameters in patients with advanced human immunodeficiency virus disease. 146 12

In the present paper the authors review the biological properties of the HIV infection. The preferential target of HIV infection is the lymphocyte that expresses the CD4 phenotype. Infection of CD4 subsets leads to a remarkable cytopathic effect that can be blocked by antibodies anti CD4 epitope. Actually the HIV envelope proteins recognize an epitope of the CD4 surface molecules; as consequence the antibodies anti idiotypic directed to CD4 indirectly present the binding of envelope proteins to CD4. The relationship between this retrovirus and the immunological pathogenesis of the disease are also discussed. HIV infection is facilitated in groups affected by alterations of the immune system as drug abusers, haemophiliacs and homosexuals. Secondary immunological abnormalities are consistently pronounced in people seropositive for the virus and affected by a progressive generalized lymphoadenopathy (PGL). The degeneration of primary lymphatic organs causes a reduction of the T-cell response against any antigenic challenge. After the PGL phase the disease shifts on AIDS, that is an irreversible stadium accompanied by the deterioration of the clinical status and by an increase of immunosuppression that favours the arise of tumours. In addiction HIV infection may cause severe central nervous system (CNS) dysfunctions, the HIV associated neurological syndromes include myelopathy, meningitis, encephalitis and peripheral neuropathy. HIV has also been isolated from brain tissue and from cerebral spinal fluid.
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PMID:Biological aspects of HIV infection. 156 58

Thirty patients with AIDS without symptoms or signs of peripheral neuropathy were compared electrophysiologically with 23 age and sex matched healthy controls. The patients had a mean reduction in the amplitude of common peroneal compound muscle action potentials of 37% (95% CI 11-70%) and of sural sensory action potentials of 34% (CI 18-49%). Mean conduction velocity of both motor and sensory nerves was reduced by between 1 and 7 m/s, with a prolongation of F waves corrected for height of 5% in the arms and 13% in the legs. The distal motor latencies were unchanged. These changes did not correlate with the duration of AIDS, degree of immunosuppression (CD4 count), Body Mass Index, albumin or vitamin B12 level. Four patients had subclinical mononeuropathies. Sural nerve taken at necropsy from five asymptomatic AIDS patients had evidence of axonal degeneration without inflammation or demyelination. There was a mean reduction in myelinated fibre density of 30.5% (CI 10-51%) compared with eight age matched sudden death controls (p = 0.01). This loss principally affected the larger fibres. The pathological and electrophysiological changes indicate axonal degeneration and are similar to those seen in other chronic disorders and in normal ageing. It is concluded that this axonal degeneration is not specific to HIV.
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PMID:Subclinical peripheral nerve involvement in AIDS: an electrophysiological and pathological study. 164 45


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