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With the advent of highly active antiretroviral therapy (HAART), the care of AIDS patients has drastically changed. Patients achieve partial immune reconstitution, appear capable of coming off medication and in many cases do not seem to have recurrences of cytomegalovirus (CMV).12 However, a risk period remains for the first few months after initiating HAART.3 The length of this period remains debatable, as does the best approach to monitor patients at risk
In their paper in this issue of the BJO (p837), Zambarakji and colleagues have attempted to clarify these two issues. By reviewing longitudinally 1292 patients for their CD4 counts and HIV loads, they were able to show that recurrences and new lesions are more commonly observed in the first 6 months after starting HAART, and that after 12 months of therapy recurrences were not observed, even in patients with detectable HIV loads and low CD4 counts. While this confirms that sufficient immune reconstitution develops to prevent CMV retinitis some time after the first 6 months of HAART, the authors correctly state that their screening methodology is inadequate to identify patients at risk.
This last statement is of considerable importance for two reasons. Firstly, if an adequate screening methodology were available, only patients at risk for CMV retinitis during HAART induction would require follow up and treatment. Secondly, we would more easily identify patients, currently being treated with HAART, that are at risk for CMV retinitis. Cases of HAART resistance or non-compliance are increasingly being reported. A recent study suggested that for ritonavir and indinavir the rate of non-compliance with non-detectable serum drug levels was in the order of 12%.4 Emergence of new resistant HIV strains occurs rapidly in patients failing HAART, requiring frequent therapy modifications.5
Luckily, no significant increase in the incidence of CMV retinitis has yet been reported in this patient population, but an appropriate screening strategy is needed. With the current low incidence of CMV retinitis, such a strategy can only be developed by studying patients starting on HAART therapy. Understanding the factors leading to a specific immune reconstitution against CMV may pave the way to new monitoring strategies for patients at risk.