Discontinuation Of anti-CMV Therapy Research Articles

Predictors for Recurrence of Cytomegalovirus Retinitis in HIV-Negative Patients

ABSTRACT Purpose To investigate the incidence of and predictive factors for recurrent cytomegalovirus retinitis (CMVR) in human immunodeficiency virus (HIV)-negative patients. Methods A retrospective review of HIV-negative patients who were newly diagnosed with CMVR between January 2005 and February 2019. Results Of 28 patients (44 eyes), 35.9% of eyes had a recurrence of CMVR after discontinuation of anti-CMV therapy. The incidence of CMVR recurrence was 17 per 100 eye-years. The factors significantly associated with CMVR recurrence were eyes with retinitis area of more than 25% (P = .013), absence of vitreous haze (P = .003), neutropenia at presentation (P = .001), and absence of systemic immunosuppression therapy prior to presentation (P = .002). Conclusion Eyes with a large area of retinitis, absence of vitreous haze, and neutropenia at presentation are predictive of CMVR recurrence while receiving systemic immunosuppression prior to CMVR presentation has a lower risk of CMVR recurrence.

Long-term Follow-up of Cytomegalovirus Retinitis in Non-HIV Immunocompromised Patients: Clinical Features and Visual Prognosis

To evaluate clinical features and long-term visual outcome of cytomegalovirus (CMV) retinitis in patients without human immunodeficiency virus (HIV) infection, and to determine factors that predict visual outcome. Retrospective cohort study. Consecutive patients with CMV retinitis without HIV infection were reviewed. Main outcome measures included clinical features, proportion of eyes with 6-month and final visual acuity (VA) <20/70 and <20/400, and odds ratios of factors associated with poor visual outcome. A total of 20 eyes from 13 patients were included with a median follow-up time of 17months. All had at least 6months of follow-up except 1 patient who died from sepsis at 1month. At presentation, 50% of eyes had VA <20/70 and 25% had VA <20/400. Zone 1 involvement occurred in 55% and vitreous haze ≥grade 2+ occurred in 25%. Recurrence occurred in 33.3% at a mean time of 6.4 ± 3.3weeks after discontinuation of anti-CMV therapy. The retinal detachment rate was 21.7% per eye-year and mortality rate was 11.7% per person-year. At final visit, 60% had VA <20/70 and 35% had VA <20/400. Macular involvement was significantly associated with poor final VA <20/400 (odds ratio= 25.00, P= .016). CMV retinitis without HIV infection was often aggressive at presentation. Significant intraocular inflammation was not uncommon. The long-term visual outcome was poor, especially in those with macular involvement.

Long-term control of CMV retinitis in a patient with idiopathic CD4+ T lymphocytopenia

Cytomegalovirus (CMV) retinitis with idiopathic CD4(+) T lymphocytopenia (ICL) is rare and difficult to control. We report a first case for long-term control of CMV retinitis with ICL using interleukin-2 (IL-2) therapy and succeeded in discontinuation of anti-CMV therapy. A 49-year-old Japanese woman was diagnosed with ICL based on low CD4(+) count (72/μl), negative for HIV-1 and -2 antibodies, and absence of any defined immunodeficiency diseases or immunosuppressive therapy. PCR test of the aqueous humor in the right eye was suggestive of CMV retinitis. She was treated with systemic ganciclovir, but after several relapses of CMV retinitis, rhegmatogenous retinal detachment appeared in the right eye and she became blind in that eye. Three years later, she developed CMV retinitis in the left eye. Although she received systemic and focal anti-CMV treatments, the retinitis showed no improvement. Finally, retinal detachment occurred, and she underwent vitrectomy. IL-2 was injected to increase CD4(+) counts. Because of hyperpyrexia, blepharedema, central scotoma, and color anomaly, we changed to low-dose IL-2 therapy with no side effects. Finally, we succeeded in increasing the CD4(+) count to more than 200/μl after discontinuation of low-dose IL-2 therapy. CMV retinitis never recurred after discontinuation of anti-CMV therapy, with good visual acuity of 20/20 in the left eye. She developed blindness of the first affected right eye, whereas the visual acuity of the left eye remains excellent more than 12years after the onset of CMV retinitis through the combined use of anti-CMV therapy, IL-2 therapy, and vitrectomy.

Cytokine profile in response to Cytomegalovirus associated with immune recovery syndrome after highly active antiretroviral therapy

Background: Several changes have occurred in the presentation and course of cytomegalovirus (CMV) retinitis in patients with AIDS since the introduction of HAART (highly active antiretroviral therapy). In some individuals who take HAART, retinitis is kept under control even after the discontinuation of anti-CMV therapy However, many of these patients develop intraocular inflammation. Uveitis, cataract, vitreitis, cystoid macular edema, epiretinal membrane, and disc edema may occur in patients with immune recovery syndrome (IRS). Methods: We evaluated the CMV-specific immune response in 55 patients by assessing CMV-specific lymphocyte proliferation, cytotoxicity, and cytokine production and correlated it with the clinical outcome. Results: Our data suggest that control of CMV retinitis is associated with acquisition of cytotoxic and lym ph op ro life rati ve responses to CMV. In addition, the upsurge of macular and disc edema seems associated with the production of interleukin-4 and tumor necrosis factor-a, whereas vitreitis is associated with the production of interleukin-2 and interferon-γ. Interpretation: The type of T-cell response that develops after HAART may determine the side effects of immune recovery and these effects are predictable based on the lymphokine profile produced by CMV-specific cells.

The Safety of Discontinuation of Maintenance Therapy for Cytomegalovirus (CMV) Retinitis and Incidence of Immune Recovery Uveitis Following Potent Antiretroviral Therapy

Background: Reconstitution of immune function during potent antiretroviral therapy can prompt discontinuation of maintenance cytomegalovirus (CMV) therapy but has also been associated with sight-threatening inflammatory conditions including immune recovery uveitis (IRU). Method: Patients with inactive CMV retinitis and a CD4+ cell count above 100/mm3, receiving CMV therapy and stable combination antiretroviral therapy, were assigned to one of two groups based on willingness to discontinue CMV therapy. Results: Thirty-eight participants were enrolled: 28 discontinued anti-CMV therapy (Group 1) and 10 continued CMV treatment (Group 2). Median on-study follow-up was 16 months. One Group 1 participant who experienced an increase in plasma HIV viral load and a decline in CD4+ cell count developed confirmed progression of CMV retinitis. Progression or reactivation CMV retinitis was not observed among Group 2. IRU was present at study entry in 3 participants. Six participants in Group 1 and 3 participants in Group 2 developed IRU on-study. CMV viremia was not detected in any participants, and urinary shedding of CMV was intermittent. Conclusion: Recurrence of CMV retinitis following discontinuation of anti-CMV therapy among patients with antiretroviral-induced increases in CD4+ cell count was rare. However, IRU was common in both those who maintained and discontinued anti-CMV therapy.

CHARACTERIZATION OF REACTIVATION OF CYTOMEGALOVIRUS RETINITIS IN PATIENTS HEALED AFTER TREATMENT WITH HIGHLY ACTIVE ANTIRETROVIRAL THERAPY

To delineate the immune parameters associated with reactivation of cytomegalovirus (CMV) retinitis in patients for whom highly active antiretroviral therapy (HAART) was not successful. Prospective, longitudinal observational study of a cohort of 102 patients with CMV retinitis treated with HAART and being followed up at the AIDS Ocular Research Unit of the University of California, San Diego from November 1995 to November 1998. The study included serial clinical and fundus photographic examinations with CD4 T-lymphocyte counts and HIV viral load measurements. Forty-seven of the 102 patients with CMV retinitis responded to HAART. Thirty-five of the patients were successfully withdrawn from anti-CMV therapy. During a median follow-up of 74.71 weeks (range, 4.86-144 weeks) after discontinuation of anti-CMV therapy, four patients experienced a reactivation of CMV retinitis. In each case, the CD4 count decreased before reactivation to a median of 31.5 cells/mm3 (mean, 31.25 cells/mm3; range, 23-39 cells/mm3). The association between the CD4 count decreasing to less than 50 cells/mm3 and reactivation of CMV retinitis was statistically significant (P < 0.0003). Four patients treated with HAART experienced reactivation of CMV retinitis as their CD4 count decreased. The threshold CD4 count below which reactivation of CMV retinitis occurred in patients for whom HAART was not successful appeared to be 50 cells/mm3. Despite an initial response to HAART, patients are still at risk for reactivation of CMV retinitis if their CD4 count decreases to less than 50 cells/mm3. The HIV viral load did not appear to predict CMV reactivation.

Lack of reactivation of cytomegalovirus (CMV) retinitis after stopping CMV maintenance therapy in AIDS patients with sustained elevations in CD4 T cells in response to highly active antiretroviral therapy.

The suppression of human immunodeficiency virus (HIV) replication and elevation in CD4 cells observed with protease inhibitor combination regimens known as HAART (highly active antiretroviral therapy) may allow AIDS patients to undergo an immune recovery that allows them to suppress the progression of cytomegalovirus (CMV) retinitis. Eleven AIDS patients receiving HAART with healed CMV retinitis in whom CMV-specific maintenance therapy was discontinued were studied. Median CD4 cell counts were 42 before the initiation of HAART and 183 at discontinuation of anti-CMV therapy. While a median 1.1 log10 drop in plasma HIV-1 RNA was obtained between starting HAART and withdrawal of maintenance therapy for CMV, only 3 of 11 patients maintained plasma HIV RNA below the limits of detection. Reactivation of CMV retinitis after withdrawal of anti-CMV therapy did not occur in any of the patients observed for a median of 156 days (range, 92-558).