Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Over the past two decades, the recognition of viral enzymes and proteins that can serve as molecular targets of drugs has revolutionized the treatment of viral infections. Beginning with acyclovir, a number of systemically administered agents which are both relatively safe and effective for the treatment of herpetic infections and human immunodeficiency virus (HIV) infections have become widely available. Because of increased numbers of herpes virus infections, as well as the rising epidemic of HIV infections, the ophthalmologist is, more likely than ever before to be involved in the treatment of severe and frequent ocular infections caused by herpes viruses. In addition, the acute retinal necrosis (ARN) syndrome has been demonstrated to be caused by herpes viruses and a once rare retinal infection caused by cytomegalovirus is common in patients with the acquired immunodeficiency syndrome (AIDS). In this article, four systemic antiviral drugs (Vidarabine, Acyclovir, Ganciclovir, and Foscarnet) that have demonstrated usefulness in the treatment of ophthalmic disease are reviewed in detail with regard to their mechanisms, applications, effectiveness, and side effects.
 ...
PMID:Systemic antiviral drugs used in ophthalmology. 132 32

Epstein-Barr virus infection (EBV) was discovered 25 years ago in tumour cells from Burkitt's lymphoma. Extensive virological studies have relieved that EBV causes infectious mononucleosis and contributes to the pathogenesis of Burkitt's lymphoma and nasopharyngeal cancer. Atypical courses of the primary infection may induce meningoencephalitis or hepatitis and are attracting increasing attention. Antiviral treatment with acyclovir has been administered for 7 days, intravenously or orally, in the early stages of infectious mononucleosis, in 2 placebo controlled trials. An inhibition of oropharyngeal EBV replication was verified but minimal effects on clinical symptoms was observed. A combination of intravenous acyclovir and prednisolone treatment for 10 days was therefore tried in 15 patients with fulminant mononucleosis in a pilot study. A transient cessation of virus shedding was noticed in all patients, and a substantial clinical effect on pharyngeal symptoms and on fever was seen in 12/15 patients within 3 days. Treatment with chemotherapy or irradiation is recommended in EBV-associated B-cell lymphomas seen in immunosuppressed, transplanted, or human immunodeficiency virus-seropositive patients. No effect of acyclovir has been reported, but such therapy may be considered in the early stage when EBV induces a polyclonal B cell activation. Acyclovir treatment is effective in the EBV-genome positive hairy leukoplakia noticed in human immunodeficiency virus-seropositive patients. However, no effect of any antiviral therapy has been reported in the X-linked lymphoproliferative syndrome affecting in particular 2-7 year old boys. Prophylactic use of immunoglobulin or acyclovir has been suggested in susceptible children. These results indicate that the variety of clinical manifestations induced by EBV at least partly depend on the immune response elicited in the host and not of virus replication per se. Therefore, treatment of these various disorders cannot be generalized but must be based on the use of antiviral drugs combined with immunomodulatory agents.
 ...
PMID:Clinical aspects on Epstein-Barr virus infection. 166 50

Herpes simplex infection of the genitals is a common condition, more often due to herpes simplex virus (HSV) type 2 than to type 1 virus. There is a severe first attack followed by mild recurrences which are more common and more frequent after HSV-2 than after HSV-1 genital infection. Clinical features with prodrome, vesicles and erosions may be characteristic allowing rapid clinical diagnosis. When possible laboratory confirmation should be attempted. General management includes simple hygiene, avoidance of sexual transmission, use of condoms, and notifying partners. Oral acyclovir (Zovirax, Wellcome) is the drug of choice for initial attacks and should be considered for all women with this diagnosis. Intravenous acyclovir may be used for very severe attacks. Men with initial attacks may be treated with oral acyclovir but mild disease affecting only skin may be treated with 5% acyclovir cream. Recurrences are short so acyclovir has less effect. Frequent recurrences can be troublesome and may be suppressed by continuous oral acyclovir, or individual attacks may be aborted with intermittent therapy. Various systemic complications may occur; an important but rare problem is primary herpes in late pregnancy. Acyclovir is effective in the treatment of the troublesome herpes simplex disease associated with human immunodeficiency infection. Acyclovir is one of the more expensive treatments for sexually transmitted diseases. At present in many countries costs are being examined, and application of the principles outlined here should help to minimize cost and maximize care.
 ...
PMID:Management of genital herpes simplex infection. 195 14

In a retrospective study of 421 patients infected with human immunodeficiency virus, 15 (3.5%) had varicella. Twelve patients had a typical varicella. Complications were as follows: profuse eruption, 6; hemorrhagic eruption, 1; hepatitis, 5; and pulmonary involvement, 1; 1 patient developed an intravascular disseminated coagulation and died of varicella. Three patients with acquired immunodeficiency syndrome, having a history of varicella, presented with an atypical form of varicella with a small number of disseminated cutaneous poxlike lesions; 1 of these patients experienced three relapses of atypical varicella. Assay of serum antibodies to varicella zoster virus showed that, while typical varicella was the primary varicella zoster virus infection, atypical varicella was a reactivation of varicella zoster virus infection. Acyclovir was given to 11 patients and vidarabine to 1 patient. The one patient who died and the one who suffered a relapse had received acyclovir. Thus, varicella in patients infected with human immunodeficiency virus may be complicated and even lethal. Atypical forms of varicella could be, as is the case with herpes zoster, a reactivation of endogenous varicella zoster virus.
 ...
PMID:Varicella in patients infected with the human immunodeficiency virus. 220 Mar 49

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.
 ...
PMID:Acyclovir-resistant varicella zoster virus infection after chronic oral acyclovir therapy in patients with the acquired immunodeficiency syndrome (AIDS). 229 95

Intravenous acyclovir and vidarabine were compared in the treatment of varicella-zoster virus (VZV) infection in 25 immunocompromised children--13 with acute lymphocytic leukemia, three with other types of cancer, two with immunodeficiency and in seven undergoing prednisolone treatment. Thirteen had varicella and 12 had herpes zoster. Acyclovir was given intravenously to five patients with varicella and to four with herpes zoster at a dose of 5-10 mg/kg every eight hours. Vidarabine was given intravenously to eight patients with varicella and to eight with herpes zoster at a dose of 10 mg/kg/day. In varicella, vidarabine significantly shortened the time from the start of treatment to cessation of new lesion formation compared with acyclovir. However, there was no significant difference in time to complete crusting between the two treatments. In herpes zoster, acyclovir significantly shortened the time from the onset of the skin lesions to complete crusting. A slight raise of GOT in two cases was reported. While acyclovir and vidarabine were equally effective for VZV infection, in herpes zoster acyclovir was more effective.
 ...
PMID:Comparison of acyclovir and vidarabine in immunocompromised children with varicella-zoster virus infection. 251 97

Both oral and intravenous acyclovir administration for seven days in the early stages of infectious mononucleosis caused an inhibition of oropharyngeal Epstein-Barr virus (EBV) replication. Minimal effect on clinical symptoms was observed. Development of normal cellular and humoral EBV-specific immunity was seen in all patients. The combination of intravenous acyclovir and prednisolone treatment for 10 days in 11 patients with fulminant mononucleosis caused transient cessation of virus shedding in all patients. A dramatic clinical effect on pharyngeal symptoms and on fever was seen in nine of 11 patients within 72 hours. Treatment with chemotherapy or irradiation is recommended in EBV-associated B cell lymphomas seen in immunosuppressed, transplanted, and human immunodeficiency virus-I seropositive patients. No effect of acyclovir has been reported, but such therapy may be considered in the early stage when EBV induces a polyclonal B cell activation. Acyclovir treatment is effective in the EBV-genome positive hairy leukoplakia in human immunodeficiency virus-seropositive patients. No effect of antiviral therapy has been reported in the X-linked lymphoproliferative syndrome. Prophylactic use of immunoglobulin or acyclovir has been suggested in susceptible children.
 ...
PMID:Management of Epstein-Barr virus infections. 284 54

18 men with longstanding human immunodeficiency virus (HIV) antigenaemia but no symptoms received zidovudine in low-dose regimens (250 mg 6-hourly, 500 mg 6-hourly, or 500 mg 12-hourly) with or without acyclovir. Serum HIV antigen rose in only 1 patient and declined significantly in 13 (to below cut-off values in 9). In the 1 subject from whom HIV antigen positive cerebrospinal fluid was obtained, the fluid was antigen negative after 12 weeks of treatment. Acyclovir treatment alone or in addition did not seem to influence serum antigen levels. In 7 untreated men serum antigen levels rose or remained stable during follow-up. CD4+ cell counts increased in 14/18 treated subjects and 1/7 untreated subjects. No disease progression was observed in either group. Regression of enlarged lymph nodes was seen in the zidovudine-treated subjects. Adverse reactions to the study drugs were infrequent and mild. Anaemia caused symptoms in 2, but serious leucopenia or neutropenia was not observed.
 ...
PMID:Effect of zidovudine on serum human immunodeficiency virus antigen levels in symptom-free subjects. 289 87

Acyclovir has become the treatment of choice for varicella-zoster virus (VZV) infections in immunocompromised individuals. This article describes a 4-year-old girl congenitally infected with human immunodeficiency virus who developed a continuous cutaneous infection with VZV that persisted over a 14-month period until her death. Initial episodes of varicella and zoster were responsive to acyclovir treatment; however, subsequent recurrences necessitated administration of multiple courses of acyclovir. Lesions became markedly hyperkeratotic, slow healing, and persistent despite acyclovir therapy. Numerous attempts to isolate virus from the lesions yielded only one isolate late in the course of therapy. This virus clearly demonstrated acyclovir resistance in vitro. Bizarre manifestations of VZV infection could present both diagnostic and therapeutic dilemmas. Prolonged acyclovir treatment of highly immunocompromised patients with acquired immunodeficiency syndrome and severe VZV may lead to the appearance of resistant virus.
 ...
PMID:Continuous varicella-zoster infection associated with acyclovir resistance in a child with AIDS. 318 52

The DNA polymerase of human herpes viruses, including cytomegalovirus (CMV), and the reverse transcriptase of human immunodeficiency virus (HIV) are selectively inhibited in vitro by the pyrophosphate analogue foscarnet. Inhibition is reversible on withdrawal of foscarnet and additive or synergistic effects have been demonstrated in vitro with other antiviral drugs, including ganciclovir and zidovudine. Foscarnet appears to have negligible effects on host enzymes and cells. Complete or partial clinical resolution of ocular symptoms is obtained in more than 89% of patients with acquired immunodeficiency syndrome (AIDS) and CMV retinitis during foscarnet induction therapy, but relapse occurs soon after ceasing treatment. Maintenance treatment given daily can extend the period of remission considerably. Foscarnet and ganciclovir monotherapy had similar efficacy in the treatment of CMV retinitis in patients with AIDS in several studies, and have been used concomitantly in immunocompromised patients with recalcitrant CMV infections. In 1 trial, patients receiving foscarnet survived for significantly longer than those receiving ganciclovir. Foscarnet has been used successfully in the treatment of limited numbers of immunocompromised patients with CMV-associated gastrointestinal (improvement in over 67% of patients) and other infections. Aciclovir-resistant herpes simplex infections in immunocompromised patients have also been treated successfully with foscarnet. Almost 90% of a foscarnet dose is excreted in the urine. Reversible nephrotoxicity is common during foscarnet therapy, but may be reduced by dosage adjustment and adequate hydration. Anaemia, nausea and vomiting, disturbances in electrolyte levels and genital ulceration have also been associated with administration of the drug. The different tolerability profiles of foscarnet and zidovudine facilitate the use of these agents in combination in patients with AIDS and CMV infection; whereas ganciclovir, like zidovudine, is associated with dose-limiting haematological toxicity. The apparent survival benefits seen in these patients when receiving foscarnet and zidovudine (possibly linked to synergy between zidovudine and foscarnet and/or the inherent anti-HIV activity of foscarnet), appear to offer potentially important advantages for foscarnet over ganciclovir in the treatment of selected patients with AIDS and CMV infections.
 ...
PMID:Foscarnet. A reappraisal of its antiviral activity, pharmacokinetic properties and therapeutic use in immunocompromised patients with viral infections. 752 25


1 2 3 4 Next >>