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* CMV Retinitis in AIDS
 #432665  
  kaizer - 07/28/09 17:14
 
  how wud U treat ?  
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* Re:CMV Retinitis in AIDS
#1826650
  prachu - 07/28/09 17:30
 
  with gancyclovir..if resistance to gancyclovir then foscarnet  
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* Re:CMV Retinitis in AIDS
#1826673
  kaizer - 07/28/09 17:44
 
  but ganciclovir causes agranulocytosis , isnt containdicated in aids pts ?  
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* Re:CMV Retinitis in AIDS
#1826690
  samomcos - 07/28/09 17:55
 
  well. I'd just call it - between the devil and the deep blue sea... but yeah, Ganciclovir, and then Foscarnet.  
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* Re:CMV Retinitis in AIDS
#1826703
  fexofenadine - 07/28/09 17:59
 
  No it is not. It is given along with HAART. It can also be given as intravitreal injections. GCSF can be coadministered to decrease the incidence of neutropenia

http://emedicine.medscape.com/article/1227228-treatment
 
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* Re:CMV Retinitis in AIDS
#1826708
  fexofenadine - 07/28/09 18:02
 
  Exactly samomcos, we have to take the risk to prevent blindness.  
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* Re:CMV Retinitis in AIDS
#1826714
  kaizer - 07/28/09 18:04
 
  kinda confused since I read it somewhere in UW , as an CI , anyway , thanx  
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* Re:CMV Retinitis in AIDS
#1826730
  esternon007 - 07/28/09 18:14
 
  Ganciclovir
 
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* Re:CMV Retinitis in AIDS
#1826740
  greatscore - 07/28/09 18:18
 
  Here guys some updating about CMV Tx :
CMV Retinitis:

Cytomegalovirus (CMV) is a ubiquitous DNA virus that infects the majority of the adult population. In the immunocompetent host, infection is generally asymptomatic or limited to a mononucleosislike syndrome. Like many other herpesviruses, CMV remains latent in the host and may reactivate if host immunity is compromised

• Active CMV retinitis usually is found in conjunction with immunosuppression, whether from AIDS, leukemia, or use of chemotherapy. These points are important in evaluating the patient history. Rarely, CMV retinitis is the first presenting manifestation of AIDS.

In immunocompromised individuals, primary infection or reactivation of latent virus
can lead to opportunistic infection of multiple organ systems. In the eye, CMV most commonly presents as a viral necrotizing retinitis with a characteristic ophthalmoscopic appearance. Untreated CMV retinitis inexorably progresses to visual loss and blindness.
Multiple antiviral agents, delivered locally, systemically, or in combination, are currently in use to delay or arrest the progress of the disease. In addition, highly active antiretroviral therapy (HAART) for HIV infection has revolutionized the treatment of CMV retinitis by allowing immune reconstitution in many individuals.


Pathophysiology :

Clinical CMV infection can affect multiple organ systems, including the skin (eg, rashes, ulcers, pustules), lungs (eg, interstitial pneumonitis), gastrointestinal tract (eg, colitis, esophagitis), peripheral nerves (eg, radiculopathy and myelopathy), the brain (eg, meningoencephalitis), and the eye (eg, retinitis, optic neuritis).
Presenting symptoms vary depending on the location of retinal involvement. Posterior lesions present with diminished visual acuity. More peripheral lesions initially can be asymptomatic. Floaters often are noted if significant vitritis is present. The eye usually is white and quiet.


CMV Retiitis medication :

A number of different antiviral medications are available for the treatment of CMV retinitis. Routes of delivery and adverse effect profiles vary significantly, so treatment programs are tailored to individual patients and their response to treatment. Current therapies use an induction dose to halt active disease followed by a lower maintenance dose that must be continued indefinitely unless immune recovery occurs. In recent years, several developments have drastically improved the quality of life for patients with CMV retinitis.

Valganciclovir, a prodrug of ganciclovir that possesses excellent oral bioavailability and
antiviral activity, has been shown to be effective in both the induction phase and the maintenance phase of CMV retinitis treatment. It is available in convenient once daily or twice daily dosing. Valganciclovir has largely replaced other treatments since it avoids the need for frequent IV infusions and long-term IV access ports.


Neupogen (granulocyte colony stimulating factor) can be used in conjunction with valganciclovir in patients experiencing neutropenia. This has helped to lessen one of the most common treatment terminating adverse effects of a very convenient and useful medication.


Foscarnet and cidofov:

ir are effective alternatives in the treatment of CMV retinitis. However, because of their adverse effect profiles and the lack of an orally bioavailable form, they have become second-line treatments. Intravitreal implants are used less frequently but are still needed in patients who have reactivation of retinitis despite systemic treatment or in those who cannot tolerate systemic treatment.
At this time( 2009 ), primary treatment generally consists of induction with either
valganciclo(ir (900 mg PO bid for 2-3 wk) or ganciclovir (5 mg/kg IV bid for 2-3 wk) followed by maintenance with valganciclovir (900 mg PO qd) until the CD4 count is above 100 cells/mL.

Finally, IRU has added a new postscript to the treatment of CMV retinitis. Treatment options are varied, and close follow-up by an experienced ophthalmologist is needed to guard against vision-threatening complications.

Antivirals MOA:

Direct action is to inhibit the DNA polymerase of CMV, preventing viral replication

Ganciclovir (Cytovene, Vitrasert)
Analog of guanosine, 10-100 times more potent than acyclovir versus CMV in vitro. Selectively inhibits DNA polymerase of CMV cells. Renal excretion

Foscarnet (Foscavir)
Analog of pyrophosphate. Inhibits DNA polymerase of CMV and reverse transcriptase of HIV. Virostatic; renal excretion. As effective as ganciclovir. Median time to relapse on Rx is 53 d. Foscarnet/ganciclovir CMV retinitis trial: 234 newly diagnosed patients randomized. Same efficacy for controlling retinitis and preserving vision


Valganciclovir (Valcyte) :
L-valyl ester prodrug of ganciclovir used to treat CMV retinitis in patients with AIDS. Ganciclovir is synthetic analogue of 2'-deoxyguanosine, which inhibits replication of human CMV in vitro and in vivo. Inhibits viral activity by inhibiting viral DNA synthesis. Has the advantage of qd or bid PO administration. Achieves levels comparable to those obtained with IV ganciclovir

Antisense medications :
Inhibit viral replication by interfering with the regulation of viral gene expression

Fomivirsen sodium (Vitravene) :
A phosphorothioate oligonucleotide. The nucleotide sequence is complimentary to the CMV viral mRNA, which encodes proteins responsible for regulation of viral gene expression. Inhibition of viral protein synthesis is achieved when fomivirsen binds the target mRNA. Second-line management

Filgrastim (Neupogen) :
Up to 40% of ganciclovir users experience dose-limiting neutropenia, which may require discontinuation. GCSF has limited this effect markedly in some studies
 
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