Risk of immune recovery uveitis in patients with AIDS and cytomegalovirus retinitis.

OBJECTIVE: To evaluate the prevalence of and risk factors for immune recovery uveitis (IRU) in eyes of patients with AIDS and cytomegalovirus (CMV) retinitis. DESIGN: Enrollment data from a 19-clinical center cohort study. PARTICIPANTS: Three hundred seventy-four patients with AIDS and CMV retinitis affecting 539 eyes. METHODS: Patients with AIDS were enrolled at 19 United States AIDS ophthalmology clinics. Data were collected by interview, review of medical records, ophthalmic examination, and phlebotomy. MAIN OUTCOME MEASURE: Immune recovery uveitis. RESULTS: Thirty-six patients (9.6%) were diagnosed with IRU involving 50 eyes. The CD4+ T-cell count of 31 of these had risen by > or =50 cells per microliter above nadir to a level > or = 100 cells per microliter (immune recovery), making up 17.6% of the patients known to have immune recovery after diagnosis of CMV retinitis (95% confidence interval, 12.3%-24.1%). No patients with IRU were observed to have active retinitis or detectable CMV DNA in peripheral blood (P<0.001 and P<0.001 with respect to patients without IRU). Other factors associated with IRU were > or =25% retinal area (odds ratio [OR], 2.72; P = 0.014) or posterior pole involvement with CMV retinitis (odds ratio, 0.43; P = 0.039), treatment with intravitreous injection of cidofovir (OR, 10.6 with respect to eyes never exposed to intravitreous or IV cidofovir; P<0.001), and male gender (OR, 0.26; P = 0.012). More eyes with IRU had visual acuity (VA) of 20/50 or worse (38.0% vs. 26.3%, P = 0.077) relative to eyes without IRU, but the proportions with VA of 20/200 or worse were similar (14.0% vs. 13.8%, P = 0.96). Eyes with IRU more commonly had cystoid macular edema (CME) (45.5% vs. 3.7%, P<0.001) and epiretinal membrane (48.9% vs. 13.3%, P<0.001) than eyes without IRU. CONCLUSIONS: Among eyes of patients with immune recovery, the prevalence of IRU is substantial. Eyes with IRU have a high risk of additional morbidity over and above that seen with CMV retinitis, with several-fold higher risk of CME and epiretinal membrane. Large CMV lesions and use of intravitreous cidofovir are risk factors for IRU.

High dose oral ganciclovir treatment for cytomegalovirus retinitis.

BACKGROUND: The oral formulation of ganciclovir is approved at a dose of 3.0 g/day for maintenance treatment of cytomegalovirus (CMV) retinitis following an initial induction course of intravenous (IV) anti-CMV therapy. Median time to progression of CMV retinitis is 12-20 days shorter with oral compared to IV ganciclovir maintenance, likely due to the limited oral bioavailability of ganciclovir. OBJECTIVES: We hypothesized that higher systemic drug exposures associated with increased doses of oral ganciclovir would be associated with increased efficacy. STUDY DESIGN: Maintenance treatment of CMV retinitis with higher than standard doses of oral ganciclovir (>3.0 g/day) was studied in 281 AIDS patients with previously treated, stable retinitis randomized to 3.0, 4.5 or 6.0 g/day oral, or 5 m/kg/day IV ganciclovir. Graders unaware of treatment assignments determined retinitis progression using fundus photographs. Vision, other ophthalmic measures and safety were assessed open-label. RESULTS: Median days to photographic progression were 41, 50, 57 and 70, respectively (P=0.052; 3.0 g vs. IV). Hazard ratios for progression relative to IV were 1.66, 1.28 and 1.19 (P=0.016 for 3.0 g). NONMEM-modeled estimates of average serum ganciclovir concentration area under the curve (AUC(0-24)) correlated best with time to progression (P=0.0019). Six grams per day oral ganciclovir was most similar in efficacy to IV, although broad confidence intervals prevented a conclusive comparison. Patients receiving oral ganciclovir had a lower frequency of sepsis and IV catheter events. CONCLUSIONS: This study suggests that the efficacy of ganciclovir for the maintenance treatment of CMV retinitis improves with increasing total drug exposure (measured as average serum concentration AUC(0-24)). All four regimens of ganciclovir were reasonably well tolerated, with safety profiles similar to what has been reported in prior work.