Cytomegalovirus retinitis

Cytomegalovirus (CMV) retinitis is the most common opportunistic ocular infections in patients with AIDS. Epidemiologic studies have estimated that 38% of patients with AIDS will develop CMV retinitis sometime between AIDS diagnosis and death. CMV retinitis is a late stage manifestation of AIDS and is associated with low CD4+ T cell counts. The incidence of CMV retinitis in patients with CD4+ T cell counts <100 cells/μl is approximately 10% per year, and with CD4+ T cell counts <50 cells/μl, 20% per year. With the availability of primary prophylaxis for CMV retinitis, researchers are focusing on using new technologies to identify a subgroup at high risk for the development of CMV retinitis. Quantitative PCR of CMV DNA from either peripheral blood cells or plasma of HIV-infected patients correlates with the presence of CMV retinitis. Branch chain DNA assays are being evaluated for similar correlations. Randomized controlled clinical trials have reported efficacy for ganciclovir, foscarnet, cidofovir, and the ganciclovir intraocular device in the treatment of CMV retinitis. Comparative trials have reported equal efficacy for ganciclovir and foscarnet in controlling the retinitis, but one trial reported a longer survival among patients treated with foscarnet, possibly due to a modest anti-HIV effect. Local therapy, such as the ganciclovir intraocular device, is highly effective for control of CMV retinitis but is associated with an incidence of contralateral ocular disease of 50% at 6 months and visceral disease of 30%. Future clinical trials will evaluate combinations of a local ocular therapy and more conveniently administered systemic therapy. Resistance to ganciclovir has been reported in 38% of patients who were treated for over three months and had positive cultures. Resistance to ganciclovir appears to be due largely to a mutation in the UL97 gene, a phosphotransferase, which is responsible for the first phosphorylation of ganciclovir to ganciclovir triphosphate. Resistance due to the mutations in this DNA polymerase gene are less common. The long-term implications of primary prophylaxis on the development of ganciclovir resistance remain undefined.