Advances in CMV Management: Fomivirsen (Vitravene®) Approved

The Food and Drug Administration recently approved a new treatment for cytomegalovirus (CMV) retinitis, an opportunistic infection affecting people with advanced HIV disease. Left untreated, CMV can lead to blindness.

Fomivirsen (Vitravene®, formerly ISIS 2922) is given by injection directly into the eye by an ophthalmologist (eye specialist) every 2 or 4 weeks. The recommended dose is 330µg on days 1 and 15 during the initial phase of treatment (when CMV is still spreading). It is then given once monthly during the maintenance phase (when CMV is not actively spreading but requires therapy to prevent it from reactivating). Studies show fomivirsen works equally well in people with newly diagnosed CMV retinitis as in those receiving other CMV therapies.

Since fomivirsen blocks CMV from replicating through a different mechanism than that of other approved CMV retinitis therapies, people who have developed resistance to other therapies may still benefit from this drug. Because fomivirsen is administered directly into the eye, it does not cause any systemic (throughout the body) side effects. However, in some studies, some people had retinal detachments. In one study that employed a higher dose in people with newly diagnosed CMV retinitis, some developed retinal stippling (spots in the retina) which resulted in some loss of peripheral vision. The fact that it works only locally in the eye also prevents the drug from suppressing CMV infections elsewhere in the body, a limitation not shared by most other treatments for CMV retinitis.

Though there have been no results directly comparing fomivirsen with other approved therapies, the results from studies so far suggest it is comparable in effectiveness to intravenous ganciclovir (Cytovene®), foscarnet (Foscavir®) and cidofovir (Vistide®) in suppressing and preventing the recurrence of active CMV retinitis. However, the ganciclovir implant (Vitrasert®), which is surgically implanted into the eye and slowly releases ganciclovir, has demonstrated much longer lasting anti-CMV retinitis effects. Nonetheless, fomivirsen is a welcome addition to the arsenal of anti-CMV therapies, especially because of its ability to work after resistance develops to other CMV therapies.

500mg Ganciclovir Capsule

A new 500mg capsule of ganciclovir (Cytovene®) is now available for use in the prevention and maintenance treatment of CMV disease. Previously, oral ganciclovir was only available in 250mg capsules, and when used for prevention or maintenance of CMV disease, required 12 capsules a day (1,000mg three times a day). This new 500mg capsule will reduce by half the number of pills needed daily.

Oral ganciclovir is poorly absorbed into the body and therefore is considered second-line therapy for the maintenance of CMV disease. However, because all other systemic therapies for CMV are administered intravenously (directly into the vein), many people opt for oral ganciclovir because it does not require a surgically implanted catheter, which is accompanied by a risk of serious bacterial infections.

Oral ganciclovir is also sometimes used for prevention of CMV disease in people with severely compromised immune systems, but this use of the drug remains controversial because of conflicting study results. More importantly, the success of HAART today in partially restoring immune function has diminished the need for preventive use.

A new formulation of oral ganciclovir, sometimes known as proganciclovir or valganciclovir, is currently in studies. This new formulation is so much better absorbed by the body that the sponsor hopes it may eventually eliminate the need for intravenous therapy altogether.

Nevirapine in Children

Nevirapine (Viramune®), a non-nucleoside reverse transcriptase inhibitor, has recently been approved for use in children. Like other antivirals, the optimal use of this drug is as part of a three-drug combination. Nevirapine should never be used alone, and its use even in two-drug combinations is discouraged because of the risk of rapid development of drug resistance.

In adult studies, nevirapine has been combined with two nucleoside analogues, such as AZT and ddI, and AZT and 3TC, in a "protease sparing" regimen. Presumably, it can also be combined with d4T and 3TC or ddI and d4T, though it has not been formally studied in this fashion. Other common adult uses include salvage therapy, in which nevirapine is added along with other new drugs after a protease inhibitor combination has failed.

The recommended dose of nevirapine for children aged 2 months to 8 years is 4mg/kg once a day for the first 14 days followed by 7mg/kg given twice a day thereafter. For children 8 years or older, the recommended dose is 4mg/kg once a day for fourteen days followed by 4mg/kg given twice a day thereafter. Children generally experience the same side effects seen in the adult studies. Rash, usually mild to moderate in severity, is the most common. Other possible side effects include fever, nausea, headache and abnormal liver function tests. One side effect only seen in children was an anemia called granulocytopenia (a reduction in granulocytes, a type of white blood cell).

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