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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The development of new antiviral agents has gained increasing momentum. It has kept pace with the identification of specific sites ("targets") in the virus replicative cycle at which potential antiviral drug can interact. The current armamentarium of available antiviral drugs consists of amantadine and rimantadine (against influenza A), ribavirin (against respiratory syncytial virus infection), idoxuridine and trifluridine (against herpetic keratitis), vidarabine and acyclovir (against herpes simplex virus infections), ganciclovir (against cytomegalovirus infections) and Retrovir (against AIDS). Various new compounds have been found which selectively inhibit those viruses [i.e. adenovirus, varicella-zoster virus, thymidine kinase-deficient (TK-) herpes simplex virus strains, and rhinoviruses] that are insensitive or poorly sensitive to the presently available antivirals. Several new compounds have also proven active against human immunodeficiency virus, the causative agent of AIDS; and, as a spin-off of the search for anti-AIDS drugs, new agents may also be expected that are effective against other retrovirus infections as well as hepadnavirus (i.e. hepatitis B virus) infections.
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PMID:New acquisitions in the chemotherapy of viral infections. 216 18

We demonstrate for the first time the appearance of acyclovir resistance in serial varicella zoster isolates from a patient treated with acyclovir. We recovered varicella zoster virus three times over a period of 5 months from the skin lesions of this patient with AIDS who was treated with three courses of intravenous acyclovir and prolonged low-dose oral acyclovir. The isolate recovered from a typical zoster lesion before acyclovir, and one obtained from a hyperkeratotic lesion 2 months later, after intravenous and oral acyclovir, were sensitive to acyclovir and produced normal amounts of thymidine kinase. In contrast, virus recovered from lesions 5 months after the onset, when the patient had received repeated courses of acyclovir, was acyclovir-resistant and thymidine-kinase-deficient. Resistance to acyclovir was associated with persistence of lesions which failed to improve with intravenous acyclovir, but was not associated with new lesion formation.
AIDS 1990 Jun
PMID:Emergence of acyclovir-resistant varicella zoster virus in an AIDS patient on prolonged acyclovir therapy. 216 3

Acyclovir (ACV)-resistant herpes simplex virus type 2 (HSV-2) was isolated from a patient with acquired immunodeficiency syndrome after long-term but intermittent ACV therapy. These thymidine kinase-defective isolates were sensitive in vitro to foscarnet. While combined therapy with ACV and interferon produced only partial clinical improvement, the in vitro effect of this combination against an ACV-resistant isolate from the patient was strongly synergistic. A short course (10-12 days) of intravenous foscarnet controlled severe ulceration, and clinical improvement lasted 6 months. After recurrence and further courses of foscarnet, however, the patient responded poorly, and subsequent HSV isolates were resistant to both ACV and foscarnet and hypersensitive to aphidicolin.
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PMID:Altered sensitivity to antiviral drugs of herpes simplex virus isolates from a patient with the acquired immunodeficiency syndrome. 216 40

Infection with acyclovir-resistant herpes simplex-virus is now a clinical reality in patients with AIDS or who are otherwise immunocompromised. The most common mechanism of resistance is selection of mutants with inability to express thymidine kinase activity. Vidarabine, foscarnet and gancyclovir can be used to treat infections with acyclovir resistant virus. In recent years there have been many reports of drug resistance from the treatment of other virus infections too.
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PMID:[Acyclovir-resistant herpes simplex virus]. 217 Nov 55

Zidovudine-resistant Escherichia coli were isolated from faecal samples from 6 out of 11 AIDS patients receiving zidovudine. Resistance appeared to be due to the loss of thymidine kinase activity which is required for the phosphorylation of zidovudine to its active form. No zidovudine resistant enterobacteria were isolated from 30 control faecal samples. Hence, clinically, there appeared to be a high correlation between the development of zidovudine-resistance in E. coli and exposure to zidovudine (chi 2: 11.77, P less than 0.001). However the development of zidovudine resistance does not appear to be associated with cross-resistance to other antimicrobial agents as the zidovudine-resistant E. coli did not display a high degree of resistance to other antibacterials.
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PMID:Isolation of zidovudine resistant Escherichia coli from AIDS patients. 222 49

The human immunodeficiency viruses (HIVs) primarily infect CD4+ T lymphocytes, leading eventually to the development of a systemic immune dysfunction termed acquired immunodeficiency syndrome (AIDS). An attractive strategy to combat HIV-mediated pathogenesis would be to eliminate the initial pool of infected cells and thus prevent disease progression. We have engineered a replication-defective, conditionally cytotoxic adenovirus vector, Ad-tk, whose action is dependent on the targeted expression of the herpes simplex virus type 1 thymidine kinase gene (tk), cloned downstream of the HIV-1 long terminal repeat, in human cells expressing the HIV-1 transcriptional activator Tat. Infection of Tat-expressing human HeLa or Jurkat cells with Ad-tk resulted in high-level tk expression, which was not deleterious to the viability of these cells. However, in the presence of the antiherpetic nucleoside analog ganciclovir, Ad-tk infection resulted in a massive reduction in the viability of these Tat-expressing cell lines. As adenoviruses are natural passengers of the human lymphoid system, our results suggest adenovirus vector-based strategies for the targeted expression, under the control of cis-responsive HIV regulatory elements, of cytotoxic agents in HIV-infected cells for the therapy of HIV-mediated pathogenesis.
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PMID:Selective induction of toxicity to human cells expressing human immunodeficiency virus type 1 Tat by a conditionally cytotoxic adenovirus vector. 224 44

Four patients with human immunodeficiency virus (HIV) infection who received chronic oral acyclovir therapy for suppression of recurrent varicella zoster or herpes simplex virus infection developed persistent disseminated hyperkeratotic papules that failed to heal with intravenous or high-dose oral acyclovir therapy. Varicella zoster virus, resistant to acyclovir in vitro, was isolated from skin lesions of all four patients. Three patients were adults in whom the acquired immunodeficiency syndrome (AIDS) had been diagnosed 12 to 20 months before isolation of acyclovir-resistant varicella zoster virus. The fourth patient was a perinatally HIV-infected child who developed primary varicella infection at age 7 years when profoundly immunosuppressed (absolute CD4+ lymphocyte count less than 50 cells/microL). Mean antiviral susceptibilities (ED50 values) of the four clinical isolates compared with the ED50 values of the reference strain Oka were 85 compared with 3.3 mumol/L for acyclovir, 1.4 compared with 0.8 mumol/L for vidarabine, and 123 compared with 117 mumol/L for foscarnet. When assayed by [125I]-dC plaque autoradiography, 90% to 100% of the viral isolate populations had altered or no measurable thymidine kinase function. Acyclovir-resistant varicella zoster virus infection may complicate long-term oral acyclovir administration in patients with AIDS and may be associated with the appearance of atypical hyperkeratotic papules.
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PMID:Acyclovir-resistant varicella zoster virus infection after chronic oral acyclovir therapy in patients with the acquired immunodeficiency syndrome (AIDS). 229 95

Two patients with acquired immunodeficiency syndrome who developed severe ulcerative proctitis caused by herpes simplex virus type 2 that was resistant to acyclovir were successfully treated with 6 weeks of high-dose, continuous-infusion acyclovir sodium (1.5 to 2.0 mg/kg per hour). Viruses cultured from the lesions were resistant to acyclovir in vitro after the patients had received prolonged therapy with oral and intravenous acyclovir in traditional divided doses. Investigation into the mechanism of the acyclovir resistance revealed changes in the thymidine-kinase activity of both isolates. This viral enzyme phosphorylates acyclovir and is necessary for drug activation. The first patient's isolate was deficient of all thymidine-kinase activity, while the second patient's isolate had a thymidine kinase with altered substrate specificity for acyclovir. The continuous infusion was safe, well tolerated, and done in an outpatient setting with weekly clinic visits and monitoring of creatinine and acyclovir levels.
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PMID:Treatment of resistant herpes simplex virus with continuous-infusion acyclovir. 230 4

HIV is the causative agent of AIDS. The purpose of this study was to examine the biochemical pharmacology of the anti-viral agent zidovudine (AZT) in the T-cell origin line (CEM). We have shown that zidovudine is activated by thymidine kinase (TK) in CEM cells to the triphosphate anabolite, which is incorporated into DNA. One microM zidovudine is sufficient for saturation of activation by TK and also of zidovudine monophosphate, by thymidylate kinase, to the diphosphate. Zidovudine triphosphate peaked 4 h after initiation of drug administration in CEM cells and then declined biexponentially. Nucleoside triphosphate (NTP) cellular concentrations declined rapidly in the cells after exposure to zidovudine. Concomitantly phosphorylation of zidovudine to zidovudine monophosphate and zidovudine monophosphate to zidovudine diphosphate declined in a similar manner in the CEM cells. The amount of zidovudine anabolite incorporated into purified DNA peaked 1 h after zidovudine treatment and declined thereafter with first order elimination kinetics. These studies elucidate the cellular activation of zidovudine in a T-cell line, CEM, and enhance our understanding of this important anti-HIV drug.
AIDS 1989 Jul
PMID:Biochemical pharmacology of zidovudine in human T-lymphoblastoid cells (CEM). 250 44

Serum thymidine kinase (S-TK) was measured weekly in 16 randomly selected patients with AIDS or AIDS-related complex (ARC; Centers for Disease Control group IV A or group IV C-2) who participated in a controlled study of the efficacy of zidovudine therapy. S-TK increased significantly (P less than 0.01) in the zidovudine group, whereas it remained stable in the placebo (control) group. On the basis of this observation, the value of S-TK measurements as a predictor of bone marrow toxicity during zidovudine therapy was investigated in 42 patients with AIDS or ARC who received zidovudine as part of their usual treatment. There was a significant association between S-TK, haemoglobin and neutrophil counts measured after the first 4 weeks of therapy and the risk of developing bone marrow toxicity during the following 6 months. Combined, measurements of S-TK and neutrophil counts seem to be well suited for the identification of patients who have a high probability for developing bone marrow toxicity during zidovudine treatment.
AIDS 1989 Nov
PMID:Serum thymidine kinase--a marker of bone marrow toxicity during treatment with zidovudine. 251 80


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