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Relapse of CMV retinitis in an AIDS patient with high CD4 counts.

Sir, We describe here a patient infected with the human immunodeficiency virus (HIV) who suffered a relapse of cytomegalovirus (CMV) retinitis despite a marked increase in her CD4 count following the initiation of treatment with combined antiretroviral therapy that did not include a protease inhibitor. The patient, a 37 year old female, was hospitalized in May 1996 with a 14 day history of blurred vision in the left eye. CMV retinitis was diagnosed, foscarnet was administered and the retinitis resolved within 3 weeks. The patient had been diagnosed as having the acquired immunodeficiency syndrome (AIDS) 2 months previously when she developed Kaposi’s sarcoma. One month before admission, she was found to have CMV viraemia and, during the course of that month, her pp65 CMV blood antigen concentration rose from 30 to 540 positive cells/2 10 peripheral blood mononuclear leucocytes (PBMLs). She was taking no antiretroviral therapy at the time of her admission for retinitis. Between June and November 1996, the patient’s medication comprised zidovudine 500 mg/day, didanosine 400 mg/day, co-trimoxazole 960 mg/day and ganciclovir 3 g/day. In December, her absolute CD4 count rose to 527/mm (from 88/mm in May and 191/mm in August) and the plasma HIV-RNA load was low ( 2 10 copies/L, compared with 2.6 10 copies/L in August). CMV antigens were present in the bloodstream in very low levels (2 positive cells/2 10 PBMLs) in August, but viraemia was not detected between May and October. In November, the ganciclovir was discontinued. Within 20 days, viraemia was once again detected and, 1 week later, the patient experienced a relapse of the retinitis in the left eye. The retinitis responded to a 3 week course of induction therapy with intravenous ganciclovir, followed by maintenance therapy with oral ganciclovir which was administered until June 1997, at which time an intraocular ganciclovir implant was inserted into the left eye. The patient remained free of CMV disease 10 months after the relapse. CMV retinitis is a common opportunistic disease in AIDS patients. Prolonged remissions (up to 8 months) with ganciclovir implants suggest that early reactivation of retinitis in patients receiving systemic treatment is the result of sub-therapeutic intravitreal concentrations, rather than the emergence of resistant strains. The patient described here probably experienced a local reactivation of CMV disease, although, when the maintenance therapy was discontinued, there was recurrence of the viraemia 3 weeks before clinical relapse was detected. Moreover, relapse occurred despite the patient’s CD4 count having risen to 527/mm—more than ten-fold greater than the count of 50/mm that is regarded as the threshold for the development of CMV disease. Combined regimens of antiviral agents are often associated with significant increases in CD4 counts. The proliferative response of the PBMLs of HIV-infected patients to a panel of mitogens, recall antigens and activating antibodies, before and 10 weeks after initiating combined antiretroviral therapy that included the protease inhibitor, ritonavir, has been studied previously in a prospective, placebo-controlled trial. The incidence of improvement (expressed in terms of the increase in the proliferative response of the PBMLs in at least one of the quantitative tests performed) was 50% in the ritonavir group, compared with 18% in the placebo group. There was also a trend towards higher response rates when the plasma HIV-RNA load was low. Although the patient described here did not receive a protease inhibitor, the proliferative response of her PMBLs to a panel of mitogens and recall antigens was normal in February 1997 and an immunological defect relating specifically to CMV was excluded. It is also noteworthy that relapse of the retinitis occurred 7 months after the initiation of combined therapy. This is in contrast to those patients who developed acute CMV infection or viraemia within 10 weeks of the initiation of combined antiretroviral therapy that included a protease inhibitor. In conclusion, we have described CMV retinitis in an AIDS patient who relapsed despite a marked increase in her CD4 count following the initiation of treatment with antiretroviral therapy that did not include a protease inhibitor. There is clearly a need for more reliable methods to facilitate the identification of patients who are at risk of experiencing reactivation of CMV disease, despite having high CD4 counts.