HIV: Opportunistic infections, treatment of Cytomegalovirus

This virus of the herpes group can cause retinitis, pneumonitis, encephalitis and colitis. Ganciclovir (Cymevene®), foscarnet (Foscavir®), valganciclovir (Valcyte®) and cidofovir (Vistide®) are used in the treatment. These products are too expensive for use in developing countries. Ganciclovir is a nucleoside analogue [nucleoside = base + saccharide] and must be coupled intracellularly to 3 phosphate groups in order to be activated. The first phosphate is coupled by a viral kinase. The next two phosphate groups are attached by a cellular enzyme. The kinase of the virus can mutate and hence resistance can occur. Cidofovir is a nucleotide analogue [nucleotide = base + saccharide + phosphate] and must be coupled to 2 phosphate groups by cellular enzymes in order to be activated. Ganciclovir can be administered IV, PO or intraocularly. Its side-effects are haemato- and nephrotoxicity. When kidney function is reduced ganciclovir® is given in a dosage of 2 x 5 mg/kg/day (infusion over 1 hour). Maintenance therapy is 5 mg/kg/day for 7 days per week or 6 mg/kg/day for 5 days per week. In the West, maintenance therapy is often given via a Port-a-cath. Vitrasert is a minuscule shield impregnated with ganciclovir that can be surgically inserted into an eye, producing high concentrations in loco. Preventive oral ganciclovir therapy for CMV leads to resistance in 23% after one year. When kidney function is normal, treatment with foscarnet -a pyrophosphate analogue-, 180-200 mg/kg/day (normally 2 x 250 ml for an average adult, diluted for peripheral infusion) can be given as an alternative. The dose for maintenance therapy is 120 mg/kg/day. The principal side-effect of foscarnet is nephrotoxicity. Fomivirsen is an experimental anti-CMV product that is still being evaluated. Monthly maintenance eye injections of fomivirsen (Vitravene) are evaluated for resistant CMV retinitis. Lobucavir and adefovir (bis-POM-PMEA) are still in an experimental stage.

Category: Medical Subject Notes , Medicine Notes , Pharmacology Notes