Therapeutic developments in cytomegalovirus retinitis

The incidence of cytomegalovirus (CMV) retinitis in AIDS has declined signi ficantly due to the use of highly active antiretroviral therapy (HAART). Ho wever, patients with HIV, especially those failing HAART, may still suffer with CMV retinitis, which can lead to significant loss of vision and blindn ess. Ganciclovir has traditionally been considered the recommended treatmen t for CMV retinitis; hoprever, due to side effects and the possibility of d eveloping viral resistance, other agents may be preferred in certain situat ions. Foscarnet, which as similar efficacy to ganciclovir but a different s ide effect profile, is more difficult to administer and is less well-tolera ted. Intravenous cidofovir, which may be more effective than either iv, gan ciclovir 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 intraoc ular ganciclovir implant has the highest efficacy of the approved agents an d is well-tolerated. Fomivirsen, an oligonucleotide injected intravitreally , is a newly approved agent which offers alternative treatment. Intravitrea l ganciclovir or foscarnet, although not approved, have been used successfu lly in some patients especially those with recurrent or refractory disease. The development of new anti-CMV agents has been stalled by the decreased i ncidence of the disease. Valganciclovir, a prodrug of ganciclovir, offers e xcellent oral bioavailability and is the closest to approval of all the new anti-CMV drugs. High ganciclovir blood levels are achieved without the com plications associated with the requirement for long-term iv. access. The mo noclonal antibody (mAb) MSL-109, did not offer a significant advantage when added to traditional anti-CMV therapy. Development plans of other agents s uch as cyclic HPMPC and lobucavir have been put on hold by their respective manufacturers. Adefovir is a nucleotide analogue that possesses anti-CMV a ctivity, but is currently only being pursued for the treatment of hepatitis B virus. Other compounds possessing significant anti-CMV activity, includi ng BAY 38-4766 and GW1263W94 are still in the early stages of development.