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)

Valaciclovir is an aciclovir pro-drug considerably improving its oral availability. Its antiviral activity in vivo is related to that of aciclovir, the principle target of which is the herpes virus. Following digestive absorption, valaciclovir is rapidly transformed into aciclovir. The mean absolute bioavailability of aciclovir is of 54.2% after a single oral dose of 1,000 mg of valaciclovir, i.e., a bioavailability 3 to 5-fold greater than after oral ingestion of aciclovir. The plasma pharmacokinetic profile of valaciclovir and aciclovir observed in volunteers infected by HIV is superimposable on that of healthy subjects. In elderly patients, exposure to aciclovir is enhanced, probably because of the alteration in glomerular filtration. In patients exhibiting agranulocytosis following poly-chemotherapy, the pharmacokinetic parameters are superimposable on those observed in healthy patients. In patients with hepatic failure, there appears no need to adapt the dose, since exposure to aciclovir does not appear altered. However, the dose of valaciclovir must be adapted to renal function. During the first-episode of herpes genitalis, valaciclovir, at the dose of 500 or 1,000 mg twice daily, is as effective as 200 mg of aciclovir five times per day. In recurrent herpes genitalis, 500 mg twice daily of valaciclovir is as effective as 1,000 mg twice daily or 200 mg five times a day of aciclovir. Valaciclovir prevents recurrence herpes genitalis with a dose-dependent effect, and doses of 500 and 1,000 mg/day are as effective as 400 mg twice daily of aciclovir. There are few studies on the efficacy of valaciclovir in the treatment of oro-facial herpes. In the treatment of herpes zoster in patients aged over 50, the principle benefit provided by valaciclovir at the dose of 1,000 mg twice daily, is the decrease in the percentage of patients presenting post-zoster pain and its duration. High doses of valaciclovir (8 capsules/day) provide efficient prevention of infections related to the cyto-megalo-virus (CMV) in immunodepressed patients due to HIV infection or following renal transplantation. Tolerance to valaciclovir, like its active metabolite aciclovir, is generally good. Central neurological toxicity is frequently observed with high doses, but regresses on withdrawal. The official indications in France are the curative and preventive treatment of herpes genitalis infections, the prevention of post-zoster pain and the ocular complications of ophthalmologic herpes in immunocompetent adults, and the prevention of CMV infections after organ grafting.
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PMID:[Valaciclovir]. 1212 13

The World Health Organization clinical criteria for AIDS diagnosis in Africa include Kaposi's sarcoma, Herpes zoster, Herpes simplex, and pruritic maculopapular rash, which have a predictive value for HIV seropositivity of 71-98%. Skin conditions may be classified as: 1) generalized dermatitis, 2) bacterial, fungal, viral, and parasitic infections, and 3) skin tumors. Pruritic maculopapular rash (prurigo) is often the first outward sign of HIV infection. Soothing preparations such as calamine lotion or E45 emollient cream can be applied. Occasionally antihistamine may be necessary, e.g., 10 mg of chlorpheniramine 8 hourly. Skin lesions may become secondarily infected with bacteria; usually Staphylococcus aureus and Streptococcus species. Persistent folliculitis or carbuncles should be treated with flucloxacillin 250 mg QDS for 7 days. In HIV/AIDS fungal infections often develop secondary infection. Candidiasis (thrush) is caused by yeasts, mainly Candida albicans and a small percentage by Tolurosis glabrata. Many HIV-infected patients suffer from seborrheic dermatitis. Fungal diseases more typically present as ringworms of the scalp (Tinea capitis). Whitfield's ointment is effective for ringworm. Antifungal creams such as miconazol or clotrimazole and systemic antifungal tablets such as ketoconazole, fluconazole, and itraconazole are also effective. Gentian violet lotion twice daily and Acyclovir tablets, 200 mg 5 times daily for 5 days, may help to reduce secondary Herpes simplex infection. HIV has been associated with an increased incidence of Herpes zoster (shingles). It is often necessary to give analgesics like aspirin or paracetamol to control the pain. Gentian violet paint may help to prevent secondary infection. When shingles affects the eye, Acyclovir tablets (800 mg 5 times daily) should be given. Kaposi's sarcoma affects wider age groups, and it is disseminated and more aggressive than the endemic type. Treatment options include radiotherapy and systemic cytotoxics such as vincristine. Intralesional injections of the drug interferon have also given successful results with some patients.
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PMID:Skin conditions common to people with HIV infection or AIDS. 1234 34

Forty-three consecutive cases of acute aseptic meningitis (AAM) presenting within a 24-months period were retrospectively analysed with respect to clinical symptomatology, cerebrospinal fluid (CSF) findings, clinical course, treatment and outcome. Nineteen of the 43 AAM cases (44%) were caused by enterovirus, one by HIV (2%), two by Varicella zoster virus (5%), three due to herpes simplex virus I (7%), two due to herpes simplex virus II (5%), one due to Central European encephalitis virus (2%), and in 15 patients (35%) the aetiology of AAM remained unknown. Headache (100%) and fever (93%) were the presenting symptoms in the majority of cases. Signs of preceding infection were predominantly gastrointestinal in the enterovirus subgroup, but were inconsistently observed in the other subgroups. CSF findings at the first lumbar tap on admission generally revealed lymphomonocytic pleocytosis of less than 500 cells per micro l, mild to moderately elevated protein and normal lactate and glucose levels. Initial therapy consisted of an empirical antiviral and antibiotic regimen until a serological diagnosis was available. Acyclovir, effective only in herpes family viruses, was initially administered to all AAM cases. Effective therapy for other viral pathogens are not broadly available and treating AAM of unknown aetiology imposes a particular problem. The average hospitalization time ranged from 16 to 31 days. Patients were either discharged home (72%) or transferred to a rehabilitation centre (28%). The outcome was good (40%) to fair (51%) in the majority of cases.
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PMID:A retrospective clinical, laboratory and outcome analysis in 43 cases of acute aseptic meningitis. 1275 1

Myeloradiculitis is a rare neurological complication of herpes simplex type 2 (HSV-2) infection, frequently associated with a fatal outcome. Among patients with HIV infection, HSV-2 myeloradiculitis has occasionally been reported, always associated with advanced immunosuppression and AIDS. We report a patient with HIV infection but no history of previous opportunistic infections, who developed sacral myeloradiculitis immediately after an episode of genital herpes. Magnetic resonance imaging with gadolinium showed necrotizing myelitis in the conus medullaris and enhancement of sacral roots. CD4 lymphocyte count was 530/mm3. Other possible causes of myeloradiculitis in HIV-infected patients were appropriately excluded. Acyclovir therapy resulted in partial clinical improvement. This report shows that myeloradiculitis as a complication of genital herpes may occur in the early stages of HIV infection and may have a favourable outcome with antiviral treatment.
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PMID:Sacral myeloradiculitis complicating genital herpes in a HIV-infected patient. 1580 49

Valaciclovir (Valtrex, Zelitrex), the L-valine ester of aciclovir, increases aciclovir bioavailability by 3- to 5-fold over that achievable with oral aciclovir. It addresses many unmet needs of currently available anti-herpesvirus therapies. Valaciclovir extends the efficacy of aciclovir in the treatment of herpes zoster and genital HSV infections, using less frequent dose regimens but retaining the highly acceptable safety profile established for aciclovir. The potential for valaciclovir in CMV prophylaxis has now been proven, and further refining to identify the optimal dose regimen is ongoing. After oral administration, valaciclovir is rapidly absorbed and extensively converted to aciclovir and L-valine, the essential amino acid. The mode of action and spectrum of antiviral activity of valaciclovir are thus identical to aciclovir. The bioavailability of aciclovir after valaciclovir, characterised from studies in healthy adult volunteers, is similar in a wide range of patient populations, including the elderly, those with advanced HIV disease, patients with impaired liver or renal function, or undergoing bone marrow transplantation. No clinically significant drug interactions with valaciclovir have so far been identified. Dosage reductions in clinical use of valaciclovir are only necessary when renal function is severely impaired. In controlled clinical trials in herpes zoster, valaciclovir (1000 mg three times daily) is superior to aciclovir in speeding the resolution of zoster-associated pain and post-herpetic neuralgia. It is as effective as aciclovir in hastening rash healing. In patients with ophthalmic zoster, no differences were evident between valaciclovir and aciclovir treatment on zoster-associated pain or the occurrence of ocular complications. The safety profiles of valaciclovir, aciclovir and placebo were not different in this study programme. In a series of controlled, randomised trials of valaciclovir, aciclovir and placebo for the acute treatment of genital HSV infections in approximately 3000 patients, twice daily valaciclovir was proven as effective as the standard 5 times daily aciclovir regimen in resolving the clinical signs and symptoms of lesional disease. Early patient-initiated valaciclovir therapy (500 mg twice daily) of recurrent genital herpes episodes was shown significantly to increase the chance of prevention of vesicular or ulcerative lesions, a valuable clinical advantage not prospectively proven for aciclovir. When used for periods of up to one year, valaciclovir (500 mg once daily) effectively suppresses genital herpes recurrences. Long-term studies of valaciclovir for HSV suppression, evaluating doses of up to 1000 mg daily in approximately 3000 patients, about 25% of whom were HIV seropositive (CD+ > 100 cells/microl), revealed a highly acceptable clinical tolerability profile for valaciclovir that did not differ from aciclovir or placebo. There were no cases resembling thrombotic microangiopathy in these long-term studies. The aciclovir safety heritage and pharmacokinetic rationale for the development of valaciclovir have been realised through the clinical research programmes in the zoster and HSV indications. Further studies in these and related areas, including CMV prophylaxis, are in progress and aim to expand further the clinical potential of valaciclovir in the future.
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PMID:Valaciclovir: development, clinical utility and potential. 1598 1

In March 2003, a 34-year-old man with left facial palsy, dysphagia, and hoarseness treated with acyclovir suffered worsened dermatological and neurological problems. A routine blood test in early April showed the patient to be HIV-antibody positive, so he was transferred to our hospital. Blood analysis showed serum HIV-RNA at 96,000 copies/mL and a CD 4 count of 170/microL. Brain MRI taken on admission showed a T 2 high lesion in their left medulla. Acyclovir was thought to be ineffective due to reduced cell-mediated immunity because of the HIV infection, and HAART therapy was begun. After two months of HAART, skin lesions and the T 2 high lesion in left medulla improred. HIV-RNA became undetectable and the CD 4 count exceeded 500/microL. Intracellular cytokine analysis by flow cytometry showed a shift from Th 2 to Th 1 dominance. The elimination of VZV may thus have been promoted by the combination of acyclovir and HAART.
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PMID:[Varicella-zoster virus symptoms and polyneuropathy in a patient with human immunodeficiency virus infection not improved until highly active anti-retroviral therapy added to acyclovir therapy]. 1651 24

We report the case of a 35-y-old HIV-infected female, who presented fulminant varicella hepatitis and recovered under medical treatment. Varicella zoster virus is an uncommon cause of acute liver disease which occurs mainly in immunocompromised patients. Acyclovir is the cornerstone of the treatment.
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PMID:Fulminant varicella hepatitis in a human immunodeficiency virus infected patient: case report and review of the literature. 1700 42

Neurologic dysfunction complicating HIV infection may occur in up to 70% of AIDS patients. The advent of highly active antiretroviral therapy has reduced central nervous system opportunistic infections. Immune reconstitutions after highly active antiretroviral therapy also lead to atypical presentations of neurologic opportunistic infections. We report a man who developed an encephalitic illness 10 months after institution of highly active antiretroviral therapy and improvement in his CD4 count. Varicella zoster vasculitis involving the brain was suspected. Acyclovir therapy resulted in complete clinical and radiologic recovery. Symptomatic reactivation of varicella zoster infection within the encephalon during therapeutic immunologic reconstitution is rare and should be suspected, especially in patients with neurologic syndrome consistent with encephalitis with recent history of herpes zoster and multiple, discrete areas of infarct or demyelination on brain magnetic resonance imaging. The clinical and neuroradiologic features of this condition and its relevance to the immune reconstitution syndrome are discussed.
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PMID:Immune reconstitution syndrome presenting with cerebral varicella zoster vasculitis in HIV-1-infected patient: a case report. 1710 8

For most viruses, there is a need for antimicrobials that target unique viral molecular properties. Acyclovir (ACV) is one such drug. It is activated into a human herpesvirus (HHV) DNA polymerase inhibitor exclusively by HHV kinases and, thus, does not suppress other viruses. Here, we show that ACV suppresses HIV-1 in HHV-coinfected human tissues, but not in HHV-free tissue or cell cultures. However, addition of HHV-6-infected cells renders these cultures sensitive to anti-HIV ACV activity. We hypothesized that such HIV suppression requires ACV phosphorylation by HHV kinases. Indeed, an ACV monophosphorylated prodrug bypasses the HHV requirement for HIV suppression. Furthermore, phosphorylated ACV directly inhibits HIV-1 reverse transcriptase (RT), terminating DNA chain elongation, and can trap RT at the termination site. These data suggest that ACV anti-HIV-1 activity may contribute to the response of HIV/HHV-coinfected patients to ACV treatment and could guide strategies for the development of new HIV-1 RT inhibitors.
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PMID:Acyclovir is activated into a HIV-1 reverse transcriptase inhibitor in herpesvirus-infected human tissues. 1877 44

The antiviral drug acyclovir is a guanosine nucleoside analog that potently inhibits herpes simplex virus (HSV) replication. Acyclovir treatment in patients coinfected with HSV and human immunodeficiency virus (HIV) has been observed to alter disease course and decrease HIV viral load, a finding that has been attributed to indirect effects of HSV suppression on HIV replication. Based on this hypothesis, several clinical studies have recently investigated the use of acyclovir for treatment of patients coinfected with HSV and HIV or for prophylaxis against HIV transmission. In this report, we use a single round HIV infectivity assay to show that acyclovir directly inhibits HIV infection with an IC50 of approximately 5 microm. The target of acyclovir in HIV-infected cells is validated as HIV reverse transcriptase (RT) by the emergence of the RT variant V75I under the selective pressure of acyclovir. The V75I mutation is part of the multidrug resistance pathway that enhances viral resistance to many of the best RT inhibitors approved for the treatment of HIV. Biochemical analyses demonstrate that acyclovir triphosphate is a chain terminator substrate for HIV RT and can compete with dGTP for incorporation into DNA. Although acyclovir may prove a useful lead for development of new HIV treatments, the selection of resistant mutants raises a cautionary note to the use of acyclovir monotherapy in patients coinfected with HSV and HIV.
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PMID:The antiherpetic drug acyclovir inhibits HIV replication and selects the V75I reverse transcriptase multidrug resistance mutation. 1881 98


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