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

The incidence of cytomegalovirus (CMV) retinitis in AIDS has declined significantly due to the use of highly active antiretroviral therapy (HAART). However, patients with HIV, especially those failing HAART, may still suffer with CMV retinitis, which can lead to significant loss of vision and blindness. Ganciclovir has traditionally been considered the recommended treatment for CMV retinitis; however, due to side effects and the possibility of developing viral resistance, other agents may be preferred in certain situations. Foscarnet, which has similar efficacy to ganciclovir but a different side effect profile, is more difficult to administer and is less well-tolerated. Intravenous cidofovir, which may be more effective than either iv. ganciclovir or foscarnet, can also be used as a first line agent; however, it is associated with toxicity (renal and ocular) and thus needs careful use. Local therapy for CMV retinitis has been a significant advance. The intraocular ganciclovir implant has the highest efficacy of the approved agents and is well-tolerated. Fomivirsen, an oligonucleotide injected intravitreally, is a newly approved agent which offers alternative treatment. Intravitreal ganciclovir or foscarnet, although not approved, have been used successfully in some patients especially those with recurrent or refractory disease. The development of new anti-CMV agents has been stalled by the decreased incidence of the disease. Valganciclovir, a prodrug of ganciclovir, offers excellent oral bioavailability and is the closest to approval of all the new anti-CMV drugs. High ganciclovir blood levels are achieved without the complications associated with the requirement for long-term iv. access. The monoclonal antibody (mAb) MSL-109, did not offer a significant advantage when added to traditional anti-CMV therapy. Development plans of other agents such as cyclic HPMPC and lobucavir have been put on hold by their respective manufacturers. Adefovir is a nucleotide analogue that possesses anti-CMV activity, but is currently only being pursued for the treatment of hepatitis B virus. Other compounds possessing significant anti-CMV activity, including BAY 38-4766 and GW1263W94 are still in the early stages of development.
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PMID:Therapeutic developments in cytomegalovirus retinitis. 1106 Jun 72

Valganciclovir is a prodrug of ganciclovir which has been developed for the treatment of cytomegalovirus (CMV) retinitis in patients with AIDS. Oral valganciclovir is rapidly absorbed and hydrolysed to ganciclovir. The oral bioavailability of ganciclovir after oral valganciclovir administration is high. Oral valganciclovir 900 mg provides a daily exposure of ganciclovir comparable to that of intravenous ganciclovir 5 mg/kg. A single, randomised, nonblind study indicated that oral valganciclovir (900mg twice daily for 3 weeks then 900 mg once daily) and intravenous ganciclovir (5 mg/kg twice daily for 3 weeks then 5 mg/kg once daily) were equally effective in the treatment of newly diagnosed CMV retinitis in 160 patients with AIDS. Valganciclovir appears to have a similar tolerability profile to intravenous ganciclovir during induction therapy in patients with AIDS and newly diagnosed CMV retinitis. During maintenance therapy with valganciclovir, the most commonly reported adverse events included neutropenia, anaemia, thrombocytopenia, gastrointestinal (including diarrhoea, nausea, vomiting and abdominal pain), fever, headache, insomnia, peripheral neuropathy, paraesthesia and retinal detachment.
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PMID:Valganciclovir. 1146 75

Valganciclovir, an oral prodrug of the anti-cytomegalovirus (CMV) agent ganciclovir, was evaluated in a single-arm open-label safety study. AIDS patients (median CD4 lymphocyte count of 140 cells/microL) with treated CMV retinitis (N = 212) received 900-mg once-daily valganciclovir maintenance therapy with courses of 900-mg twice-daily valganciclovir induction therapy as needed to treat progression. After a median treatment duration of 372 days, the adverse event profile was similar to that reported for intravenous (IV) and oral ganciclovir. Adverse event rates of note were diarrhea (35%), nausea (23%), fever (18%), neutropenia (absolute neutrophil count <500 cells/microL) (10%), and anemia (hemoglobin <8.0 g/dL) (12%). Consistent with prior treatment studies of oral ganciclovir, IV catheter-related adverse events were uncommon (6%) and lower than previously reported for IV ganciclovir. The mortality rate was 0.072 deaths per patient-year. Progression of CMV retinitis occurred in 17% of patients during the study treatment period, usually in association with a low CD4 cell count. Other than a higher than expected frequency of oral candidiasis (17%), no clinical toxicities or laboratory abnormalities occurred during treatment with valganciclovir that have not been observed during treatment with ganciclovir.
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PMID:A safety study of oral valganciclovir maintenance treatment of cytomegalovirus retinitis. 1213 45

For AIDS patients with cytomegalovirus (CMV) retinitis, the standard initial treatment has so far been ganciclovir or foscarnet, both of which are infused intravenously. The choice between these two antiviral agents is based on their differing side effects. Maintenance treatment is based on ganciclovir or foscarnet, but both these drugs must be given as daily intravenous infusions. Oral ganciclovir is less effective. Intraocular maintenance treatment in appropriate only for patients with localised infections and a low risk of relapse. Valganciclovir can be taken orally for both initial and maintenance treatment of CMV retinitis. Valganciclovir has good bioavailability and is rapidly metabolised into ganciclovir. A comparative randomised trial in 160 patients showed that oral valganciclovir is as effective as intravenous ganciclovir when used as an initial treatment. There are no comparative trials of oral valganciclovir as a maintenance treatment, but non comparative data and pharmacokinetic studies suggest that oral valganciclovir is about as effective as intravenous ganciclovir. The adverse effects of oral valganciclovir are similar to those of intravenous ganciclovir, except that the oral route avoids the risk of local complications at the infusion site. Valganciclovir causes more frequent diarrhoea and oral candidosis than intravenous ganciclovir. In practice, for patients with CMV retinitis who require systemic treatment, oral valganciclovir is easier to use and, in our opinion, should now replace IV ganciclovir for both initial and maintenance treatment. The convenience of oral valganciclovir should also limit the use of purely intraocular treatment of CMV retinitis.
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PMID:Valganciclovir: new preparation. CMV retinitis: a simpler, oral treatment. 1290 21

Cost advantages of the oral route of drug therapy administration over the intravenous route for managing cytomegalovirus (CMV) disease are described. The overall costs usually are lower for the oral route of administration than for the intravenous route, although the cost to the patient depends on insurance coverage. Other advantages of the oral route include greater safety and convenience, which may improve patient adherence and quality of life. In patients with acquired immunodeficiency syndrome (AIDS), the use of oral ganciclovir instead of intravenous ganciclovir to treat the maintenance phase of CMV retinitis reduced the incidence of neutropenia and sepsis, outpatient and inpatient resource use, and costs. Oral therapy also improved patient quality of life. A cost-effectiveness model for liver transplant recipients found that CMV prophylaxis is warranted for all patients, ganciclovir is preferred over CMV immune globulin i.v. and oral acyclovir for prophylaxis, and the oral route of administration is more cost-effective than the intravenous route for ganciclovir. Valganciclovir, the oral prodrug of ganciclovir, was not included in this model. Oral maintenance therapy is usually cost-effective, safer, and more convenient than intravenous therapy in the management of CMV.
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PMID:Cost advantages of oral drug therapy for managing cytomegalovirus disease. 1468 29

Valganciclovir is an orally administered prodrug of ganciclovir, the most widely used drug in the clinical management of Cytomegalovirus infections. The good bioavailability and the rapid conversion into ganciclovir provide oral valganciclovir with pharmacokinetic properties approaching those of intravenously administered ganciclovir. The first-reported clinical applications confirm the efficacy of valganciclovir in the treatment of Cytomegalovirus retinitis in AIDS patients and the prophylaxis of Cytomegalovirus disease after organ transplantations, which are the currently approved indications. Broader application of valganciclovir is to be expected in the pre-emptive treatment of organ as well as stem-cell transplant recipients. This drug also increases the potential for prophylactic applications, which may lead to the development of viral resistance.
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PMID:[Valganciclovir. Oral treatment of Cytomegalovirus infections]. 1530 86

Herpes virus infections, particularly those caused by cytomegalovirus (CMV), lead to significant and, sometimes severe, clinical problems for the immunocompromised host. As effective agents have become available, several treatment and prevention strategies have evolved over the past decade, first in intra-venous form and more recently, as oral preparations. Valganciclovir, the valine ester of ganciclovir, is an orally administered, potent, antiviral agent active against all herpes viruses. When taken orally, valganciclovir has much-improved bioavailability compared with oral ganciclovir and achieves ganciclovir exposures similar to intravenous ganciclovir. Clinical trials evaluating the safety and efficacy of valganciclovir for the treatment of new AIDS-associated CMV retinitis showed equivalency to intravenous ganciclovir and prevented progression of quiescent disease. In solid organ recipients, once-daily valganciclovir has been proven equivalent to oral ganciclovir for the prevention of CMV infection. The high bioavailability and convenient dosing formulation make valganciclovir an attractive option for these indications.
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PMID:Valganciclovir: oral prevention and treatment of cytomegalovirus in the immunocompromised host. 1533 Jul 37

Valganciclovir (Valcyte, Roche), a prodrug of the deoxyguanosine analog ganciclovir (Cytovene, Roche), is indicated for induction and maintenance treatment of cytomegalovirus retinitis in patients with AIDS and for prevention of cytomegalovirus disease in selected high-risk solid organ transplant recipients. After oral administration, valganciclovir is rapidly absorbed and converted to ganciclovir by intestinal and hepatic esterases. Valganciclovir is a highly recognized substrate of the intestinal peptide transporter PEPT1, which underlies the tenfold higher bioavailability of ganciclovir after valganciclovir compared to oral ganciclovir administration. At oral dose of 900 mg, valganciclovir provides a systemic ganciclovir exposure that is comparable to intravenous ganciclovir, at the standard dose of 5 mg/kg of body weight. Subsequent phosphorylation of ganciclovir, which occurs preferentially within cytomegalovirus-infected cells, results in the active metabolite, ganciclovir triphosphate, which is responsible for suppressing viral DNA synthesis by competitively inhibiting the incorporation of the natural substrate deoxyguanosine into viral DNA and thereby, terminating cytomegalovirus replication.
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PMID:Valganciclovir for the prevention and treatment of cytomegalovirus disease in immunocompromised hosts. 1548 69

Valganciclovir (Valcyte) is an orally administered prodrug of the standard anti-cytomegalovirus (CMV) drug ganciclovir. Valganciclovir is as effective as intravenous ganciclovir for the treatment of AIDS-related CMV retinitis, and oral ganciclovir for the prophylaxis of CMV infection and disease in high-risk solid organ transplant recipients. The drug is generally well tolerated and has a similar tolerability profile to that of oral or intravenous ganciclovir, but is devoid of adverse events related to intravenous or indwelling catheter access associated with the use of intravenous ganciclovir, cidofovir and foscarnet. The simple and convenient once-daily valganciclovir regimen offers potential for improved patient compliance. It provides greater systemic ganciclovir exposure than oral ganciclovir, thus reducing the risk of viral resistance when used for prophylaxis in high-risk solid organ transplant recipients. Furthermore, the use of valganciclovir instead of intravenous ganciclovir may provide significant cost savings, based on data comparing oral versus intravenous regimens for the treatment of AIDS-related CMV retinitis. Overall, valganciclovir appears to have some advantages over ganciclovir. Therefore, when used as prophylaxis against CMV infection and disease in high-risk solid organ transplant recipients or as induction and maintenance therapy of CMV retinitis in patients with AIDS, oral valganciclovir is an attractive alternative to other available anti-CMV drugs.
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PMID:Valganciclovir: a review of its use in the management of CMV infection and disease in immunocompromised patients. 1581 97

Valganciclovir (VGC) has proved efficacious and safe for the prophylaxis against cytomegalovirus (CMV) in high-risk transplant recipients and for the treatment of CMV retinitis in AIDS patients. We used VGC for the treatment of CMV infection (viremia without symptoms) or disease (CMV syndrome or tissue-invasive disease) in kidney, heart, and lung transplant recipients. Fourteen transplant recipients were treated: five for asymptomatic CMV infection and nine for CMV disease. VGC was administered in doses adjusted to renal function for 4 to 12 weeks (induction and maintenance therapy). Clinically, all nine patients with CMV disease responded to treatment. Microbiologically, treatment with VGC turned blood culture negative for CMV within 2 weeks in all patients and was associated with a > or =2 log decrease in blood CMV DNA within 3 weeks in 8 of 8 tested patients. With a follow-up of 6 months (n = 12 patients), asymptomatic recurrent CMV viremia was noted in five cases, and CMV syndrome noted in one case (all cases in the first 2 months after the end of treatment). VGC was clinically well tolerated in all patients; however, laboratory abnormalities occurred in three cases (mild increase in transaminases, thrombocytopenia, and pancytopenia). This preliminary experience strongly suggests that therapy with VGC is effective against CMV in organ transplant recipients; however, the exact duration of therapy remains to be determined: a longer course may be necessary to prevent early recurrence.
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PMID:Treatment of cytomegalovirus infection or disease in solid organ transplant recipients with valganciclovir. 1584 85


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