Objective: To determine whether visualization of successful task completion during encoding improves performance on a naturalistic prospective memory (PM) task.Method: The sample was comprised of 60 young adults with HIV infection.Participants were administered a brief clinical neuropsychological assessment, which included a standardized performance-based measure of time-and event-based PM.All participants were also given a naturalistic PM task in which they were asked to manage a mock medication regimen when the examiner showed them the Grooved Pegboard Test during their neuropsychological evaluation.Participants were then randomized into: 1) a visualization condition in which they spent 30 sec imagining successfully completing the naturalistic PM task; or (2) a control condition in which they repeated the task instructions.Results: Multiple linear regression analyses revealed no main effects of visualization or clinical PM for naturalistic PM performance; however, there was a significant interaction between clinical PM ability and visualization condition (p , 0.05).Specifically, for participants with low time-based PM scores, the visualization intervention was associated with significantly higher naturalistic PM accuracy than was the control condition (p , 0.05).In contrast, there was no effect of visualization for participants with high time-based PM scores.There was no interaction between event-based PM and visualization.Conclusion: Findings indicate that a brief visualization exercise can support strategic encoding and performance on naturalistic PM performance in persons with HIV-associated clinical impairments in time-based PM.The extent to which such interventions improve health-related PM outcomes such as medication adherence remains to be determined.

Human immunodeficiency virus (HIV) disease is commonly associated with deficits in prospective memory (PM), which increase the risk of suboptimal health behaviours, like medication non-adherence. This study examined the potential benefits of a brief future visualisation exercise during the encoding stage of a naturalistic PM task in 60 young adults (aged 19-24 years) with HIV disease. Participants were administered a brief clinical neuropsychological assessment, which included a standardised performance-based measure of time- and event-based PM. All participants were also given a naturalistic PM task in which they were asked to complete a mock medication management task when the examiner showed them the Grooved Pegboard Test during their neuropsychological evaluation. Participants were randomised into: (1) a visualisation condition in which they spent 30 sec imagining successfully completing the naturalistic PM task; or (2) a control condition in which they repeated the task instructions. Logistic regression analyses revealed significant interactions between clinical neurocognitive functions and visualisation. HIV positive (HIV+) participants with intact retrospective learning and/or low time-based PM demonstrated observable gains from the visualisation technique, while HIV+ participants with impaired learning and/or intact time-based PM did not evidence gains. Findings indicate that individual differences in neurocognitive ability moderate the response to visualisation in HIV+ young adults. The extent to which such cognitive supports improve health-related PM outcomes (e.g., medication adherence) remains to be determined.

Objective: To evaluate patients with cytomegalovirus (CMV) retinitis treated with intravenous cidofovir for long-term outcomes.Design: Patients with CMV retinitis enrolled in a randomized, controlled clinical trial of intravenous cidofovir as treatment for retinitis were followed for long-term outcomes, including 21 patients initially enrolled in the deferral group who received cidofovir therapy after progression of retinitis.Setting: Thirteen tertiary care clinics specializing in AIDS care and ophthalmology.Participants: Fifty-eight patients with AIDS and small peripheral CMV retinitis lesions.Interventions: Cidofovir 5 mg/kg once weekly for 2 weeks followed by low-dose maintenance cidofovir therapy (3 mg/kg) in 35 patients or high-dose maintenance (5 mg/kg) in 23 patients.Main outcome measures: Time to progression of retinitis, drug toxicities.Results: Median time to progression of retinitis was 2.5 months. Median time to discontinuation of cidofovir because of intolerance was 6.6 months, and did not differ significantly between the two maintenance doses. Median time to discontinuation of cidofovir for intolerance other than probenecid reaction was 16.3 months for patients treated with low-dose maintenance and 5.0 months for patients treated with high-dose maintenance (P = 0.021). Proteinuria of 2+ or more occurred at a rate of 1.22/person year. In patients with sufficient follow-up to determine resolution of proteinuria, 89.9% of episodes resolved, and the median time to resolution was 20 days. Rates of probenecid intolerance and of cidofovir-associated uveitis were 0.35/person-year, and 0.20/person-year, respectively.

Background: Cytomegalovirus (CMV) retinitis is a common infection and a major cause of visual loss in patients with the acquired immunodeficiency syndrome (AIDS). Objective: To evaluate intravenous cidofovir as a treatment for CMV retinitis. Design: Two-stage, multicenter, phase II/III, randomized, controlled clinical trial. Setting: Ophthalmology and AIDS services at tertiary care medical centers. Patients: 64 patients with AIDS and previously untreated, small, peripheral CMV retinitis lesions (that is, patients at low risk for loss of visual acuity). Intervention: Patients were randomly assigned to one of three groups: the deferral group, in which treatment was deferred until retinitis progressed; the low-dose cidofovir group, which received cidofovir, 5 mg/kg of body weight once weekly for 2 weeks, then maintenance therapy with cidofovir, 3 mg/kg once every 2 weeks; or the high-dose cidofovir group, which received cidofovir, 5 mg/kg once weekly for 2 weeks, then maintenance therapy with cidofovir, 5 mg/kg once every 2 weeks. To minimize nephrotoxicity, cidofovir was administered with hydration and probenecid. Measurements: Progression of retinitis, evaluated in a masked manner by a fundus photograph reading center; the amount of retinal area involved by CMV; the loss of visual acuity; and morbidity. Results: Median time to progression was 64 days in the low-dose cidofovir group and 21 days in the deferral group (P = 0.052, log-rank test). The median time to progression was not reached in the high-dose cidofovir group but was 20 days in the deferral group (P = 0.009, log-rank test). Analysis of the rates of increase in the retinal area affected by CMV confirmed the data on time to progression. The three groups had similar rates of visual loss. Proteinuria of 2+ or more occurred at rates of 2.6 per person-year in the deferral group, 2.8 per person-year in the low-dose cidofovir group (P > 0.2), and 6.8 per person-year in the high-dose cidofovir group (P = 0.135). No patient developed 4+ proteinuria, but two cidofovir recipients developed persistent elevations of serum creatinine levels at more than 177 mu mol/L (2.0 mg/dL). Reactions to probenecid occurred at a rate of 0.70 per person-year. Conclusions: Intravenous cidofovir, high- or low-dose, effectively slowed the progression of CMV retinitis. Concomitant probenecid and hydration therapy, intermittent dosing, and monitoring for proteinuria seemed to minimize but not eliminate the risk for nephrotoxicity.

Objective: To evaluate the the efficacy and safety of an intravenous human monoclonal antibody to cytomegalovirus (CMV), MSL-109, as adjuvant treatment for CMV retinitis.Methods: Two hundred nine patients with acquired immunodeficiency syndrome and active CMV retinitis were enrolled in a multicenter, phase 2/3, randomized, placebo-controlled clinical trial. Patients received adjuvant treatment with MSL-109, 60 mg intravenously every 2 weeks, or placebo. Randomization was stratified on the basis of whether patients had untreated or relapsed retinitis. Primary drug therapy for CMV retinitis was determined by the treating physician.Results: The rates of retinitis progression, as evaluated in a masked fashion, were 3.04/person-year in the MSL-109-treated group and 3.05/person-year in the placebo-treated group (P=.98; Wald test); the median times to progression were 67 days in the MSL-109-treated group and 65 days in the placebo-treated group. No differences between the 2 groups were noted in the rates of increase in retinal area involved by CMV, visual field loss, or visual acuity outcomes. The mortality rate in the MSL-109-treated group was 0.68/person-year, and in the placebo-treated group, 0.31/person-year (P=.01). The mortality difference was not explained by differences in baseline variables or in concurrent antiretroviral therapy. Among patients with newly diagnosed retinitis, mortality rates were similar (MSL-109, 0.41/person-year; placebo, 0.42/person-year; P=.95), whereas among patients with relapsed retinitis the MSL-109-treated group had a greater mortality rate (MSL-109, 0.83/person-year, placebo, 0.24/person-year; P=.003). However, the mortality rate in the placebo-treated patients with relapsed CMV retinitis was lower than that in the placebo-treated patients with newly diagnosed CMV retinitis and lower than that in other trials of patients with relapsed CMV retinitis.Conclusions: Intravenous MSL-109, 60 mg every 2 weeks, appeared to be ineffective adjuvant therapy for CMV retinitis. The mortality rate was higher in the MSL-109-treated group, but the reasons for this difference remain uncertain.

Objective: To determine the best therapeutic regimen, using currently approved drugs, for treatment of relapsed cytomegalovirus (CMV) retinitis.Design: Multicenter, randomized, controlled clinical trial.Setting: Ophthalmology and acquired immunodeficiency syndrome (AIDS) services at tertiary care medical centers.Patients: Two hundred seventy-nine patients with AIDS and either persistently active or relapsed CMV retinitis.Intervention: Patients were randomized to one of three therapeutic regimens: induction with foscarnet sodium at 90 mg/kg intravenously every 12 hours for 2 weeks, followed by maintenance at a dosage of 120 mg/kg per day (foscar net group); induction with ganciclovir sodium at 5 mg/kg intravenously every 12 hours for 2 weeks followed by maintenance at 10 mg/kg per day (ganciclovir group); or continuation of previous maintenance therapy plus induction with the other drug (either ganciclovir or foscarnet) for 2 weeks followed by maintenance therapy with both drugs, ganciclovir sodium at 5 mg/kg per day and foscarnet sodium at 90 mg/kg per day (combination therapy group).Outcomes: Mortality, retinitis progression, visual acuity, visual fields, and morbidity.Results: The mortality rate was similar among the three groups. Median survival times were as follows: foscarnet group, 8.4 months; ganciclovir group, 9.0 months; and combination therapy group, 8.6 months (P=.89). Comparison of retinitis progression, as evaluated in a masked fashion by the centralized Fundus Photograph Reading Center (FPRC), revealed that combination therapy was the most effective regimen for controlling the retinitis. The median times to retinitis progression were as follows: foscarnet group, 1.3 months; ganciclovir group, 2.0 months; and combination therapy group, 4.3 months (P<.001). Although no difference could be detected in visual acuity outcomes, visual field loss and retinal area involvement on fundus photographs both paralleled the progression results, with the most favorable results in the combination therapy group. The rates of visual field loss were as follows: foscarnet group, 28 degrees per month; ganciclovir group, 18 degrees per month; combination therapy group, 16 degrees per month (P=.009), and the rates of increase of retinal area involved by CMV were as follows: foscarnet group, 2.47% per month; ganciclovir group, 1.40% per month; and combination therapy group, 1.19% per month (P=.04). While side effects were similar among the three treatment groups, combination therapy was associated with the greatest negative impact of treatment on quality-of-life measures.Conclusions: For patients with AIDS and CMV retinitis whose retinitis has relapsed and who can tolerate both drugs, combination therapy appears to be the most effective therapy for controlling CMV retinitis.