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)

In this paper we describe the in vitro antiviral activity of the (-) enantiomer of carbocyclic 2',3'-deoxydidehydroguanosine, (-) carbovir, a nucleoside analogue that has selective and potent anti-HIV activity in a series of lymphocyte culture systems. The cellular cytotoxicity of this compound has also been evaluated in a number of systems and compared to the saturated dideoxynucleoside analogues AZT and ddC.
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PMID:Carbovir: the (-) enantiomer is a potent and selective antiviral agent against human immunodeficiency virus in vitro. 167 57

A new mechanism is proposed for the apparent breakthrough of HIV that occurs approximately 6 months after the commencement of therapy with zidovudine (AZT). Using a simple mathematical model of the interacting population dynamics of HIV and its major host cell in the circulation (the CD4+ lymphocyte), predicted patterns of HIV plasma viraemia in the weeks following treatment with zidovudine are generated. These are in close agreement with observed patterns despite the fact that the model contains no mechanisms for the development of drug-resistant strains of virus. It is suggested that the patterns of viral abundance observed during the first 6 months after treatment may be the result of non-linearities in the interactions between HIV and CD4+ cells, and that it is only after the first post-treatment burst of viral production that drug resistance plays an important role.
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PMID:Population dynamics of HIV within an individual after treatment with zidovudine. 167 7

In June 1991, practicing, research, and academic dentists attended a symposium on oral research and dental treatment in HIV infection at Guy's Hospital in London, England. Oral lesions in HIV infection were classified as strongly associated, probably associated, and possibly associated with HIV infection. A speaker stressed that those strongly associated with HIV infection should be of the most interest to general dental practitioners. Another speaker said that chronic erythematous candidiasis has emerged as an oral infection strongly associated with HIV infection in addition to pseudomembranous candidiasis. A dentist mentioned hairy leukoplakia as a new condition strongly associated with HIV infection. Other HIV associated periodontal disease included gingivitis, necrotizing gingivitis, and periodontitis. A speaker noted that AZT increases longevity of AIDS patients and the drugs dideoxyinosine and dideooxycytidine are being tested. Another dentist spoke about the issue of HIV infected dentists citing the example of the dentist in Florida who infected 5 patients. Other speakers addressed the cases and needs of asymptomatic HIV infected people. A survey of dentists showed that only 33% of dentists would provide dental care to HIV infected people and only 20% would if the patients had AIDS. A dentist addressed the problem of a lack of data on prevention and treatment of oral lesions since their etiology and pathogenesis were unknown. Other presentations focused on research on antibodies and DNA probes in reference to saliva and subgingival flora. The symposium revealed the ran ge and depth of research going on in British schools on oral manifestations of HIV infection.
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PMID:Oral research and dental treatment in HIV infection. 168 36

Mismatched double-stranded RNA (Ampligen) has broad spectrum antiviral and immunomodulatory activities. These activities generate stabilization or improvement in three important surrogate markers of HIV disease progression. Patients with HIV disease treated with Ampligen do not become positive for p24 antigen, in contrast to patients treated with AZT or placebo. Viral burden can also be decreased in patients receiving Ampligen/AZT therapy. In vitro studies indicate that both AZT sensitive and AZT resistant viruses can be inhibited by Ampligen alone and are synergistically inhibited by Ampligen in combination with AZT. The immunomodulatory effects of Ampligen are manifested as a stabilization of CD4 counts. When Ampligen is combined with AZT, an increase in CD4 count is seen. Furthermore, a return or increase in delayed type hypersensitivity to mumps, Candida, and trichophyton was seen in approximately 70% of patients treated with Ampligen. The activity of Ampligen in HIV disease is due to its multifunctional activity as an antiviral and immune stimulating agent. The antiviral effect directly inhibits HIV-infection and other viruses which have been implicated in HIV disease acceleration and progression. The immunomodulatory activity can stabilize, increase, or restore immune function. This enhanced immune function can also lead to the further inhibition of additional infections associated with disease progression. Thus, Ampligen has multiple mechanisms of action against HIV disease.
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PMID:Mismatched double-stranded RNA, Ampligen (poly(I): poly(C12U), demonstrates antiviral and immunostimulatory activities in HIV disease. 168 87

As human immunodeficiency virus type 1 (HIV-1) has become better understood, numerous drugs have been developed that act at virus-specific sites. These are challenging our ability to evaluate them thoroughly and rapidly. Zidovudine (AZT) remains the mainstay of anti-HIV-1 drugs. Recent controlled trials indicate it should be used early in infection (in those with CD4 cell counts less than 500/mm3) and in lower doses (500-600 mg/day). Prolonged AZT treatment in patients with AIDS, however, is often associated with viral resistance. Newer reverse transcriptase-inhibiting nucleoside derivatives are currently in phase II-III clinical trials. Other HIV-1 replicative sites under attack in clinical studies include binding and entry of virus, envelope protein glycosylation, and viral assembly and release. Agents that target HIV-1 proteinase, integrase, ribonuclease H, and products of regulatory genes such as tat are under development. Combination therapies that target different viral replicative sites likely will allow use of individual agents below their toxic concentrations and help prevent drug resistance. Innovative programs for expanded access to experimental drugs are needed that will permit expeditious clinical trials, optimize the gathering of useful information, and permit the widest access to promising treatments.
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PMID:Chemotherapy of human immunodeficiency virus infections: current practice and future prospects. 169 Dec 43

The reverse transcriptase enzyme of HIV-1 is known to be error-prone. We were interested in the possibility of isolating a variant HIV-1 strain that might be capable of replication in the presence of AZT, thought to act by antagonizing reverse transcriptase activity. Toward this end, chronically infected H-9 cells were exposed to various concentrations of AZT for at least 500 days. No mutant has yet arisen from such cultures, which continued to produce high levels of each of the viral proteins p24, p17, gp41, and gp51/66 in the presence of the drug. Notwithstanding such expression of viral antigens, culture fluids from these various AZT-treated cultures were not capable of infecting otherwise susceptible target cells. Electron microscopic observations of AZT-treated chronically infected H-9 cells indicated a lower production of viral structures, in comparison with control cultures. Furthermore, those particles seen at the plasma membrane of AZT-treated cells often appeared to be envelope-deficient. These data suggest that AZT may be able to interfere in some way with proper assembly and/or packaging of infectious progeny HIV-1 at the cell membrane, although other modes of action for a postintegrational effect of AZT cannot be excluded.
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PMID:AZT (zidovudine) may act postintegrationally to inhibit generation of HIV-1 progeny virus in chronically infected cells. 169 85

Three analogs of thymidine, D4T [2',3'-didehydro-2',3'-dideoxythymidine; 1-(2,3-dideoxy-beta-D-glyceropent-2-enofuranosyl)thymine], FddT (3'-fluoro-3'-deoxythymidine), and AZT (3'-azido-3'-deoxythymidine), were compared in biological tests designed to assess their potential utility as anti-human immunodeficiency virus (HIV) agents. The in vitro potencies of these compounds against HIV infection in CEM cells were measured, with FddT and AZT being more potent than D4T. The cytotoxicities of D4T, FddT, and AZT for CEM cells were comparable. The triphosphates of these three derivatives inhibited purified HIV reverse transcriptase, and their affinities for this polymerase were found to be 1 or 2 orders of magnitude greater than that for the normal substrate, dTTP. D4T was less toxic than FddT or AZT for cultured human and mouse bone marrow cells (granulocyte-macrophage CFU). The three compounds had similar toxicities for human progenitor erythrocyte burst-forming units. In a 30-day mouse toxicity study, AZT and FddT produced a similar spectrum of hematopoietic toxicities. These toxic effects occurred at much lower doses of FddT than of AZT. At the higher doses of FddT, a significant incidence of lethality occurred. By contrast, D4T was considerably less toxic than both AZT and FddT in this study. The dose-limiting toxicity of D4T in mice was hepatotoxicity. The very different phosphorylation patterns of D4T, its lower toxicity, and its comparable potency relative to FddT and AZT suggest that the potential of D4T as an anti-HIV agent should be further explored.
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PMID:Comparison of in vitro biological properties and mouse toxicities of three thymidine analogs active against human immunodeficiency virus. 169 57

Sodium pentosan polysulfate (PPS), a negatively charged polymer of beta-D-xylopyranose units, was evaluated for its anti-HIV effects in normal human peripheral mononuclear cells (PMNC) and its possible synergism with AZT. In the presence of 25 nM AZT, 2.0 micrograms/ml of PPS reduced HIV-1 replication 110-fold, compared with a 3.9- and 7-fold decrease in the presence of either drug individually. Surprisingly, at low (below 1 microgram/ml) concentrations of either PPS or dextran sulfate, an enhancement of virus production was observed. PPS was nontoxic, had a proliferative effect on uninfected and a protective effect on infected PMNC. Virus enhancement at low concentrations of PPS appeared to be linked to its lymphoproliferative effect. These findings suggest that the use of PPS and others such agents as monotherapy for AIDS might have deleterious effects. However, due to its marked synergism with AZT and its lymphoproliferative activities, PPS might prove to be a useful agent in therapeutic trials of AIDS if used in combination with less than the usual dosage of AZT.
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PMID:Sodium pentosan polysulfate (PPS), an anti-HIV agent also exhibits synergism with AZT, lymphoproliferative activity, and virus enhancement. 169 54

On July 27, 1989, the International Conference on Molecular Aspects of Immune Response and Infectious Diseases devoted a symposium to the subject of the use of intravenous gamma globulin (IVIG) in acquired immunodeficiency syndrome (AIDS). The information presented confirmed that IVIG benefits human immunodeficiency virus (HIV)-infected children with recurrent infections and that much remains to be learned about the influence of IVIG in adult AIDS. The symposium participants recognized the urgent need to develop randomized clinical trials using a control group to assess the efficacy of a treatment with IVIG in PGL (persistent generalized lymphadenopathy), ARC (AIDS-related complex), and AIDS. To prepare this report, a committee was established, including individuals with expertise in immunology, immunopharmacology, microbiology, virology, infectious diseases, general medicine, and pediatrics and representing research experience in academia and hospitals. After an introduction to the report with a summary of immunotherapeutic agents under evaluation to treat HIV infection, section 1 lays out the present understanding of the disease pathogenesis. Section 2 then outlines the treatment of HIV-seropositive individuals, discussing the uncertainties that any treatment entails. Section 3 discusses the rationale for treating HIV-infected individuals with IVIG, and Section 4 examines the major differences between IVIG and hyperimmunoglobulins for the treatment of HIV infection. Section 5 looks at IVIG as a mean to delay the emergence of opportunistic infections and restore immunocompetence in AIDS and related illnesses, and Sections 6 and 7 suggest a pilot protocol on the use of IVIG in association with low-dose or standard-dose zidovudine (AZT).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Report of the symposium on the use of intravenous gammaglobulin in adults infected with the human immunodeficiency virus. 169 38

HIV-1 infection of promonocytic U937 cells was used to examined induction of IFN-alpha/beta gene expression and to determine the inhibitory effects of IFN-alpha 2 and/or AZT on de novo HIV-1 infection, initiated either by coculture of virus-shedding U9-IIIB cells with uninfected cells or by incubation of U937 cells with virus-containing supernatants. Usually 21-28 days were required to transmit virus to greater than 90% of the cell culture. HIV-1 infection did not stimulate constitutive production of endogenous IFN-alpha 1/alpha 2 or IFN-beta genes, although induction of IFN RNA was observed following coinfection with the paramyxovirus Sendai. Exogenous rIFN-alpha 2 treatment decreased the intracellular accumulation of viral RNA 5- to 20-fold as determined by Northern blot analysis and the extracellular levels of HIV-1 as measured by p24 ELISA antigen capture. The effect was most dramatic at a time coincident with the rapid increase in virus spread through the cell culture (Days 10-18). During the fourth week of infection, HIV-1 multiplication was able to overcome the IFN-induced block in virus spread. AZT was not effective in limiting virus spread in the cocultivation experiments. When U937 cells were infected with virus-containing supernatants from U9-IIIB cells, IFN and AZT acted in combination to limit the number of infected cells and to inhibit intracellular accumulation of viral RNA. These experiments suggest that subtle differences in the mode of virus transmission in monocytic cells may alter the efficacy of combination antiretroviral therapy.
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PMID:Inhibition of HIV-1 transmission by interferon and 3'-azido-3'-deoxythymidine during de novo infection of promonocytic cells. 169 54


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