Retinitis, CMV

AIDS (acquired immunodeficiency syndrome) is the final stage of disease caused by infection with HIV. In this stage, the vims infection has severely affected the immune system, causing a depletion of CD4+ T-helper cells. AIDS is characterized by the manifestation of typical diseases caused by opportunistic infections (Pneumocystis carinii pneumonia, CMV retinitis, candidiasis of the esophagus, cerebral toxoplasmosis), neurological manifestations, cachexia, or certain tumors (Kaposi sarcoma of the skin, B-cell lymphoma). 

CMV, a virus of the herpes family, isa common viral infection. Healthy individuals may beoome infected yet have no symptoms. However, immunocompromised patients (such as those with HIV or cancer) may have the infection. Symptoms include malaise, fever, pneumonia, and super infection. Infants may acquire the virus from the mother while in the uterus, resulting in learning disabilities and mental retardation. CM V can infect the eye, causing retinitis. Symptoms of CMV retinitis are blurred vision and decreased visual acuity. Visual impairment is irreversible and can lead to blindness if untreated. 

Antiviral drugp interfere with viral reproduction by altering DNA synthesis. These drug are used in the treatment of herpes simplex infections of the eye, treatment in immunocompromised patients with cytomegalovirus (CMV) retinitis, and for the prevention of CMV retinitis in patients undergoing transplant. 

However, acyclic nucleotide analogs (acyclic nucleoside phosphonates) have been developed, which carry one phosphonate moiety and require only the two subsequent phosphorylation steps (De Clercq et al. 1978). Independent of virus-encoded kinases, they display a broader spectrum of efficacy. This class comprises important drugs against HIV (tenofovir) and HBV (adefovir, tenofovir), as well as cidofovir, which is approved for use against CMV retinitis, but also displays an exceptionally broad efficacy profile against many herpesviruses, adenovirus, poxviruses, and papillomaviruses (De Clercq and Holy 2005). 

Cidofovir (Fig. 2) has been formally approved for the treatment of CMV retinitis in AIDS patients, where it is administered intravenously at a dose not exceeding 5 mg/kg once weekly during the first two weeks (and every other week thereafter). Cidofovir is also used off label for the treatment of human papilloma virus (HPV) infections (i.e., cutaneous warts, anogenital warts, laryngeal and pharyngeal papilloma), polyomavirus [i.e., progressive (i.e., multifocal leukoencephalopathy (PML)], adenovirus, herpesvirus, and poxvirus (i.e., molluscum contagiosum) infections, where it can be administered intravenously (at a dose of < 5 mg/kg once weekly or every other week) or topically as a 1% gel or cream (De Clercq and Holy 2005). Especially in immunosuppressed patients (i.e., transplant recipients), local treatment of HPV-associated lesions has often yielded spectacular results (Bonatti etal.2007). 

Antivirals are used to treat the ocular sequelae of AIDS such as CMV retinitis. They are treated with systemic administration, but with the need for higher localized ocular therapeutic concentrations, products have been developed and approved for direct administration into the vitreous cavity. 

A new antiviral agent, developed for treatment of CMV retinitis, can be administered by intravitreal injection. Formivirsen sodium is a phosphorothioate oligonucleotide that inhibits CMV replication through an antisense mechanism. It is formulated as a sterile and preservative-free solution and supplied in single-use vials (Vitravene ). The product is administered directly into the vitreous cavity posterior to the limbus through a 30-gauge needle. This procedure can be performed on an... 

Developed by the US company, Isis, Vitravene is used to treat cytomegalovirus (CMV) retinitis in AIDS patients. It is synthesized chemically and formulated as a sterile solution (6.6 mg active drug/ml) in WFI using a bicarbonate buffer to maintain a final product pH of 8.7. 

Cytomegalovirus (CMV) retinitis Treatment of CMV retinitis in patients with AIDS. Combination Combination therapy with ganciclovir for patients who have relapsed after monotherapy with either drug. 

Renal function Impairment The major toxicity of foscarnet is renal impairment, which occurs to some degree in most patients. Approximately 33% of 189 patients with AIDS and CMV retinitis who received IV foscarnet in clinical studies developed significant impairment of renal function, manifested by a rise in serum creatinine concentration to 2 mg/dL or more. 

Ganciclovir IV is indicated for use only in the treatment of cytomegalovirus (CMV) retinitis in immunocompromised patients and for the prevention of CMV disease in transplant patients at risk for CMV disease. 

Ganciclovir capsules are indicated only for prevention of CMV disease in patients with advanced HIV infection at risk for CMV disease and for maintenance treatment of CMV retinitis in immunocompromised patients. 

Because oral ganciclovir is associated with a risk of more rapid rate of CMV retinitis progression, use only in those patients for whom this risk is balanced by the benefit associated with avoiding daily IV infusions. 

For patients who experience progression of CMV retinitis while receiving maintenance treatment with either formulation of ganciclovir, reinduction treatment is recommended. 

CMV disease Safety and efficacy have not been established for congenital or neonatal CMV disease, nor for the treatment of established CMV disease other than retinitis, nor for use in nonimmunocompromised individuals. The safety and efficacy of oral ganciclovir have not been established for treating any manifestation of CMV disease other than maintenance treatment of CMV retinitis. 

Diagnosis of CMV retinitis The diagnosis should be made by indirect ophthalmoscopy. Other conditions in the differential diagnosis of CMV retinitis include candidiasis, toxoplasmosis, histoplasmosis, retinal scars, and cotton wool spots, any of which may produce a retinal appearance similar to CMV. The... 

Retinal detachment Retinal detachment has been observed in subjects with CMV retinitis both before and after initiation of therapy with ganciclovir. Its relationship to therapy is unknown. Patients with CMV retinitis should have frequent ophthalmologic evaluations to monitor the status of their retinitis and to detect any other retinal pathology. 

There has been very limited clinical experience using ganciclovir for the treatment of CMV retinitis in patients younger than 12 years of age. 

Maintenance - Following induction treatment, or in patients with inactive CMV retinitis, the recommended dosage is 900 mg (two 450 mg tablets) once daily with food. 

WARNING Renal impair is the major tox foUow administration instructions Uses CMV retinitis w/ HIV Action Selective inhibition of viral DNA synth Dose Rx 5 mg/kg IV over 1 h once/wk for 2 wk w/ probenecid Maint 5 mg/kg IV once/2 wk w/ probenecid (2 g PO 3 h prior to cidofovir, then 1 g PO at 2 h 8 h after cidofovir) X in renal impair Caution [C, -] Contra Probenecid or sulfa allergy Disp Inj SE Renal tox, chills, fever, HA, NA /D, thrombocytopenia, neutropenia Interactions t Nephrotox W/ aminoglycosides, amphot icin B, foscar-net, IV pentamidine, NSAIDs, vancomycin t effects W/zidovudine EMS Monitor ECG for hypocalcemia (t QT int val) and hypokalemia (flattened T waves) OD May cause renal failure hydration may be effective in reducing drug levels/effects Cilostazol (Pletal) TAntiplatelet, Arterial Vasodilator/ Phosphodiesterase Inhibitor] Uses Reduce Sxs of intermittent claudication Action Phosphodiesterase in inhibitor t s cAMP in pits blood vessels, vasodilation inhibit pit aggregation Dose 100 mg PO bid, 1/2 h before or 2 h after breakfast dinner Caution [C, +/-] Contra CHE, hemostatic disorders. 

Foscarnet (Foscavir) [Antiviral] Uses CMV retinitis acyclovir-resistant hCTpes Infxns Action -1- Viral DNA polym ase RT Dose CMV retinitis Induction 60 mg/kg IV qSh or 100 mg/kg ql2h X 14—21 d Meant 90-120 mg/kg/dIV (Moo.-Fiti ) Acyclovir-resistant HSV Induction 40 mg/kg IV q8-12h x 14—21 d use central line -1- w/ renal impair Caution [C, —] T Sz potential w/ fluoroquinolones avoid n hrotoxic Rx (cyclosporine, aminoglycosides, ampho B, protease inhibitors) Contra CrCl <0.4 mL/min/kg Disp Inj SE Nephrotox, electrolyte abnormalities Interactions T Risks of Sz W/ quinolones t risks of n hrotox W/ aminoglycosides, amphotCTicin B, didanosine, pentamidine, vancomycin EMS Known to cause electrolyte disturbances (extremity numbness paresthesia indicates electrol5rte unbalance) monitor ECG OD May cause extremity numbing, and Szs hydrate w/ IV fluids... 

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