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)

Antiretroviral therapy for children is still at an early stage, although progress is being made slowly. Zidovudine administered at 180 mg/m2/dose every 6 hours is the current standard therapy for symptomatic children and those with low CD4 counts. This standard is likely to evolve as further testing clarifies the optimal dosage for ZDV in different populations. Children on ZDV need to be monitored very closely (at least monthly) for hematologic side effects, which are most common in the more seriously ill children. The role of some of the newer antiretrovirals, like ddI and ddC, which are likely to be licensed, has yet to be established. They have a different toxicity profile than ZDV and thus may work well in combination with it. The issue of peripheral neuropathy and the lack of an easy test to measure it makes using ddC or ddI in young, preverbal children a daunting proposition. As with ZDV, the optimum dosage and timing have yet to be fixed for ddC or ddI alone, and even less available are regimens for combination therapy. Antiretroviral drugs other than the dideoxynucleosides are less well developed. Some, like high-titer antiviral immunoglobulin, involve technology that is already available and thus will be relatively easy to study. Others, like the antisense oligomers, are such a new technology that there are many hurdles to be overcome as the agents move from the laboratory to the clinic. The goal of agents that work on sites other than reverse transcriptase is a reasonable one, but the work in perfecting such new categories of drug is difficult and slow. In the meantime, children with HIV should be symptomatically supported and offered the most effective antiretroviral regimens available.
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PMID:Antiviral therapy for human immunodeficiency virus infection in children. 198 14

Pharmacologic and psychosocial interventions begin at the time HIV infection is diagnosed and continue to the end of the patient's life. It is important that the nurse and patient communicate effectively with one another about the significance of being HIV positive, including disease progression and treatment modalities. Symptoms of and treatments for early infection (e.g., oral candidiasis, aphthous stomatitis, staphylococcal folliculitis, and herpes zoster) are reviewed. Pneumocystis carinii infection is a major concern; pentamidine, dapsone, and trimethoprim--sulfamethoxazole may be used for prophylaxis. Regimens and guidelines for zidovudine treatment are discussed. Promising antiretroviral therapies include ddI, ddC, CD4, protease inhibitors, and compound Q. Ultimately, vaccines may be available.
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PMID:Treatment modalities for patients with HIV disease. 203 84

2',3'-Dideoxy purine nucleosides have anti-HIV activity in vitro and the inosine analogue is being clinically evaluated. The instability of these compounds toward acidic conditions complicates oral administration. The effect of the addition of a fluorine atom to the 2'-position was investigated by preparing the fluorine-containing 2'-erythro and 2'-threo isomers of ddA and the threo isomer of ddI. All fluorine-containing compounds were indefinitely stable to acidic conditions which completely decomposed ddI (1) and ddA (2) in minutes. While the fluorine-containing erythro isomer, 5, was inactive, the threo isomers, 2'-F-dd-ara-A (3) and 2'-F-dd-ara-I (4), were just as potent and active in protecting CD4+ ATH8 cells from the cytopathogenic effects of HIV-1 as the parent drugs. Exposure to pH 1 at 37 degrees C prior to testing destroyed the activity of ddA and ddI but left the anti-HIV properties of 3 and 4 unchanged. The fluorinated analogues also protected cells exposed to HIV-2 and inhibited gag gene product expression but not as effectively as the parent compounds. The fluorine-containing analogues appear to be somewhat more toxic in vitro to the antigen- and mitogen-driven proliferation of immunocompetent cells than their corresponding parent compounds.
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PMID:Acid-stable 2'-fluoro purine dideoxynucleosides as active agents against HIV. 210 81

AIDS has remained a significant and worsening medical problem since its first description as a new clinical entity in 1981. In the past 6 years, substantial progress has been made in the chemotherapy for this disease; such progress is likely to exert a major effect on the epidemic of human immunodeficiency virus infection in the coming decade. In this article, we overview the preclinical development of an antiretroviral drug, 2',3'-dideoxyinosine (didanosine; ddI), which has recently been shown in early phase I studies to have activity against human immunodeficiency virus in patients with AIDS or AIDS-related complex. Although we will not know the full clinical potential of ddI until we have the results of ongoing controlled clinical trials, this drug appears to possess desirable features for clinical use.
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PMID:Overview of the preclinical development of an antiretroviral drug, 2',3'-dideoxyinosine. 211 2

As a more complete safety profile of ddI begins to merge, it is clear that this agent continues to hold promise as an option for the treatment of primary HIV disease in certain patients. The long-term efficacy and safety of the drug can be fully understood only from the results of controlled clinical trials. To speed this process, the assistance and cooperation of all physicians in identifying and referring patients to the controlled trials is requested. Completion of these studies is essential and critical to a full understanding of the use of this drug in the treatment of patients with HIV infection.
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PMID:A note to physicians. AIDS in Arkansas. 215 Sep 60

Ninety-two adult patients with AIDS or severe AIDS-related complex were treated with 2',3'-dideoxyinosine (didanosine; ddI) at dosages ranging from 0.8 to 66.0 mg/(kg.d) for at least 6 weeks in phase I trials. Potentially beneficial changes in weight (40% of patients), clinical signs or symptoms (40% of patients), CD4+ cell counts (25% of patients), and serum levels of HIV p24 antigen (50% of antigen-positive patients) were reported. Response rates tended to be higher among patients with AIDS-related complex and among those who had not received prior zidovudine therapy. A major response (improvement in at least one clinical parameter and in at least one laboratory marker) occurred in 29% of patients, and rates of major response tended to be higher in patients receiving higher dosages. The primary dose-limiting toxicity observed was peripheral neuropathy, which was observed with increasing frequency in patients receiving greater than 20 mg/(kg.d). Of the other adverse effects, pancreatitis was possibly dose-dependent and hyperuricemia (without clinical gout) occurred only at high doses. Dosages of 250 mg and 375 mg of ddI twice daily will be used in extended phase II/III studies.
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PMID:Overview of phase I trials of 2',3'-dideoxyinosine (ddI) conducted on adult patients. 216 65

Dideoxynucleosides (zidovudine[AZT], dideoxycytidine[ddC], and dideoxyinosine[ddI]) are promising new agents for the management of human immunodeficiency virus type 1 (HIV-1) infections. In light of recent data demonstrating defects in the polymorphonuclear leukocyte (PMN) bactericidal activity of HIV-1-infected patients and since many chemotherapeutic agents affect PMN function, we examined their effects on the function of PMNs from both healthy and HIV-1-infected individuals in vitro. AZT (0.1 to 25 microM), ddC (0.01 to 1 microM), and ddI (0.2 to 50 microM) had no effect on viability, chemotaxis to N-fromylmethionyl leucyl phenylalanine, phagocytosis of Candida albicans or Staphylococcus aureus, or superoxide production following stimulation by N-formylmethionyl leucyl phenylalanine. Killing of C. albicans was not affected by AZT but was enhanced by 0.1 and 1 microM ddc (a 1 microM, killing was 26.0 +/- 2.02% compared with 17.0 +/- 0.73% for controls: P = 0.006) and 0.2 to 50 microM ddI (at 10 microM, killing was 25.0 +/- 0.68% compared with 17.8 +/- 0.91% for controls; P = 0.002). Killing of S. aureus was unchanged by AZT and ddC but was significantly enhanced by ddI at 0.2 to 20 microM (at 2 microM, killing was 71.2 +/- 5.57% compared with 51.4 +/- 6.29% for controls; P = 0.0045). In addition, the preexisting defective bactericidal capacity of PMNs from HIV-1-infected patients was enhanced by ddI (P less than 0.025). Potential enhancement by these dideoxynucleosides of certain PMN functions of HIV-1-infected patients deserves further study.
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PMID:Effects of antiretroviral dideoxynucleosides on polymorphonuclear leukocyte function. 217 34

The symptomatic HIV-infection is characterized by the involvement of multiple organs with a predominance of infectious complications. Treatment of these complications usually follows established therapeutic regimens for the resulting diseases of affected organs. Successful reconstitution of the immunodeficiency resulting from HIV-infection has been unsuccessful so far. Recently, promising results have been obtained by the treatment of patients with antiviral substances which inhibit viral replication. The prototype substance, Zidovudine (AZT) has been proven to be beneficial for patients in advanced stages of the disease and more recently has been shown to delay the occurrence of full-blown AIDS in patients with AIDS-related complex. In consequence, substances with less side effects such as Dideoxycytidine or Dideoxyinosine are currently under investigation.
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PMID:[Symptomatic HIV infection. Approaches to rational therapy]. 219 60

We have seen a dramatic increase in the types of antiviral strategies and numbers of specific antiviral agents that have emerged since the early 1980s when infection with the human immunodeficiency virus was first recognized. At the moment, zidovudine is the only drug approved by the FDA for treatment of HIV infection, and its indication is limited only to patients in the most advanced stages of immunodeficiency. Although zidovudine cannot "cure" HIV infection, it can significantly delay the seemingly inexorable course of immune system decline and buy some meaningful time for most HIV-1 infected patients, whether or not they have developed immunodeficiency. Other agents such as interferon alpha and the didoxynucleoside analogues, ddI and ddC, have also shown promise as antiretroviral agents, and it is hoped they will be proved, in the near future, capable of delaying the progression of immune system destruction by HIV-1. Other related treatment modalities such as the use of PCP prophylactic regimens also have succeeded in decreasing the incidence of opportunistic infections and thereby improving survival. It is likely that future strategies will involve the use of alternating, multidrug regimens both to reduce selective pressure for the development of drug resistance and to minimize the toxicity of single-agent therapy. The sum of these developments has been to change the prognosis of HIV infection. A disease once viewed as an automatic death warrant is now in the process of becoming a chronic, potentially long-term treatable illness.
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PMID:The role of antiretroviral therapy in living long and living well. 240 32

A series of nucleotide homo- and heterodimers [3'-azido-3'-deoxythymidilyl-(5',5')-2',3'-di-deoxy-5' adenylic acid (AZT-P-ddA), 3'-azido-3'-deoxythymidilyl-(5',5')-2', 3'-dideoxy;-5'-adenylic acid, 2-cyanoethyl ester [AZT-P(CyE)-ddA], 3'-azido-3'-deoxythymidilyl-(5',5')-2',3'-dideoxy-5'-inosinic acid (AZT-P-ddI), and 3'-azido-3'-deoxythymidilyl-(5',5')-3'-azido-3'-deoxy-5'-thymid ilic acid (AZT-P-AZT)] were synthesized and compared with respect to their anti-HIV and cytotoxic properties to their component monomers in vitro. MT-2 cells were infected with HIV (TM) followed by the addition of drug. The dimers and their respective monomers inhibited HIV-induced syncytia formation, reverse transcriptase production, and the expression of HIV p24 antigen. However, on an equimolar basis, greater anti-HIV potency and enhanced cytotherapeutic indices were observed with the heterodimers when compared with their monomers. Nucleotide dimers, such as AZT-P-ddA, should be actively considered for further evaluation as anti-HIV agents.
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PMID:Nucleotide dimers suppress HIV expression in vitro. 246 62


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