Retinite por citomegalovírus em paciente com Síndrome de Good / Cytomegalovirus retinitis in Good Syndrome

Resumo A Síndrome de Good é uma síndrome paraneoplásica caracterizada pela associação de timoma e hipogamaglobulinemia, cursando com imunossupressão. Relatamos um caso raro de retinite por citomegalovírus em paciente com esta síndrome.

Abstract Good syndrome is a paraneoplastic syndrome characterized by the association of thymoma and hypogammaglobulinemia, with immunosuppression. We report a rare case of cytomegalovirus retinitis in a patient with this syndrome.

Late emergence of A594V and L595W mutations related to ganciclovir resistance in a patient with HCMV retinitis and long-term HIV progression

The emergence of ganciclovir (GCV) resistance during the treatment of human cytomegalovirus (HCMV) infection is a serious clinical challenge, and is associated with high morbidity and mortality. In this case report, we describe the emergence of two consecutive mutations (A594V and L595W) related to GCV resistance in a patient with HCMV retinitis and long-term HIV progression after approximately 240 days of GCV use. Following the diagnosis of retinitis, the introduction of GCV did not result in viral load reduction. The detected mutations appeared late in the treatment, and we propose that other factors (high initial HCMV load, previous GCV exposure, low CD4+ cell count), in addition to the presence of resistance mutations, may have contributed to the treatment failure of HCMV infection in this patient.

Clinical features and outcomes of AIDS-related cytomegalovirus retinitis in the era of highly active antiretroviral therapy / Características e evolução clínica da retinite por citomegalovírus em pacientes com AIDS na era da terapia antirretroviral potente

PURPOSE: To describe the features and outcomes of patients with AIDS-related cytomegalovirus retinitis after highly active antiretroviral therapy availability. METHODS: Retrospective chart review of 30 consecutive patients (44 eyes) with AIDS and newly diagnosed, active AIDS-related cytomegalovirus retinitis, examined from January 2005 to December 2007. RESULTS: The mean age was 34.8 years, 18 patients (60.0 percent) were male and median duration of AIDS was 90 months. Nineteen patients (63.3 percent) had evidence of highly active antiretroviral therapy failure and median CD4+ lymphocyte count was 12.5 cells/µl. Visual acuity at presentation was 20/40 or better in 27 eyes (61.4 percent). Retinitis involved Zone 1 in 13 eyes (39.5 percent). Despite specific anti-AIDSrelated cytomegalovirus therapy, 16 eyes (36.4 percent) presented relapse of retinitis and 10 eyes (22.7 percent) lost at least three lines of vision. When compared to highly active antiretroviral therapy responsive patients, eyes of highly active antiretroviral therapy failure patients were more likely to develop relapse of retinitis (p=0.03) and loss of at least three lines of vision (p=0.03). CONCLUSION: The patients in this series are essentially young men with longstanding AIDS, non-responsive to highly active antiretroviral therapy and with a similar immunological profile as noted before highly active antiretroviral therapy era. These findings have implications for the management of the disease and confirm the magnitude of rational periodic screening after diagnosis of AIDS.

OBJETIVO: Descrever as características e evolução clínica de pacientes com retinite por citomegalovírus relacionada à AIDS após o advento da terapia antirretroviral potente. MÉTODOS: Estudo retrospectivo dos prontuários de 30 pacientes consecutivos (44 olhos) com AIDS e retinite por citomegalovírus ativa recém-diagnosticada, atendidos entre janeiro de 2005 e dezembro de 2007. RESULTADOS: A idade média dos pacientes foi de 34,8 anos, 18 pacientes (60,0 por cento) eram do sexo masculino e a mediana do tempo de diagnóstico de AIDS era 90 meses. Dezenove pacientes (63,3 por cento) apresentavam evidência de falência da terapia antirretroviral potente e a mediana da contagem de linfócitos T CD4+ era 12,5 células/µl. A acuidade visual inicial era melhor ou igual a 20/40 em 27 olhos (61,4 por cento). A retinite acometia a Zona 1 em 13 olhos (39,5 por cento). Apesar da terapia antirretinite por citomegalovírus específica, 16 olhos (36,4 por cento) apresentaram recidiva da retinite e 10 olhos (22,7 por cento) perderam pelo menos três linhas de visão. Quando comparado aos de pacientes com boa resposta à terapia antirretroviral potente, olhos de pacientes com falência à terapia antirretroviral potente apresentaram mais recidiva da retinite (p=0,03) e perda de pelo menos três linhas de visão (p=0,03). CONCLUSÃO: Os pacientes nesta série são essencialmente homens jovens com longo tempo de diagnóstico de AIDS, má resposta à terapia antirretroviral potente e com um perfil imunológico semelhante ao encontrado antes do advento da terapia antirretroviral potente. Estes achados têm implicações no manejo da doença e confirmam a importância da triagem periódica e racional após o diagnóstico de AIDS.

[Cytomegalovirus retinitis: clinical and therapeutic aspects]

CYTOMEGALOVIRUS [CMV] is a frequent infection, which is usually asymptomatic. It is a significant pathogen in terminal acquired immunodeficiency syndrome [AIDS] patients causing major opportunistic events. Retrospective study of 5 AIDS patients with CMV retinitis treated between 1990 and 2001 in the department of ophthalmology in Sfax Hospital centre was conducted to determine clinical and therapeutic featuring, and efficacy of intraveinous and intravitreal ganciclovir to control retinitis in AIDS patients. The results showed that retinitis was controlled in 4 cases and visual acuity improved within three weeks. Serious ocular complications were encountered in 1 case. Concomitant tritherapy was used in 3 cases. In 1 case we noted necrotizing retinitis at the periphery enlarging centrifugally and progressing to the fovea. In immunocompromised patients, Ganciclovir may offer good alternative to control CMV retinitis. Fortunately, with the use of highly active antiretroviral therapy very few patients have disease related to CMV

Withdrawal of maintenance therapy for cytomegalovirus retinitis in AIDS patients exhibiting immunological response to HAART

BACKGROUND: Before the introduction of highly active antiretroviral therapy (HAART), CMV retinitis was a common complication in patients with advanced HIV disease and the therapy was well established; it consisted of an induction phase to control the infection with ganciclovir, followed by a lifelong maintenance phase to avoid or delay relapses. METHODS: To determine the safety of CMV maintenance therapy withdrawal in patients with immune recovery after HAART, 35 patients with treated CMV retinitis, on maintenance therapy, with CD4+ cell count greater than 100 cells/mm³ for at least three months, but almost all patients presented these values for more than six months and viral load < 30000 copies/mL, were prospectively evaluated for the recurrence of CMV disease. Maintenance therapy was withdrawal at inclusion, and patients were monitored for at least 48 weeks by clinical and ophthalmologic evaluations, and by determination of CMV viremia markers (antigenemia-pp65), CD4+/CD8+ counts and plasma HIV RNA levels. Lymphoproliferative assays were performed on 26/35 patients. RESULTS: From 35 patients included, only one had confirmed reactivation of CMV retinitis, at day 120 of follow-up. No patient returned positive antigenemia tests. No correlation between lymphoproliferative assays and CD4+ counts was observed. CONCLUSION: CMV retinitis maintenance therapy discontinuation is safe for those patients with quantitative immune recovery after HAART.

Antes da introdução da terapia anti-retroviral altamente efetiva (HAART), a retinite por CMV era uma complicação comum em pacientes com doença por HIV avançada e a terapia era bem estabelecida e consistia em uma fase de indução com ganciclovir para controlar a infecção, seguida por uma manutenção por toda a vida, para evitar e retardar as recidivas. Para determinar a segurança da retirada da terapia de manutenção para retinite por citomegalovírus em pacientes com recuperação imunológica após o HAART, 35 pacientes com retinite por CMV tratados com terapia de manutenção, com contagem de células CD4+ maiores que 100 células/mm³ por no mínimo três meses, mas a maioria dos pacientes apresentava esses valores por mais de seis meses e carga viral < 30.000 cópias/mL, foram avaliados prospectivamente para a recorrência de doença por CMV. A terapia de manutenção foi retirada na inclusão e os pacientes foram monitorados no mínimo 48 semanas por avaliações clínicas e oftalmológicas e pela determinação de marcadores de viremia para CMV (antigenemia). Contagens de CD4+ e CD8+ e níveis de RNA de HIV no plasma. Métodos linfoproliferativos foram realizados em 26/35 pacientes. RESULTADOS: Dos 35 pacientes incluídos no estudo, somente um teve reativação da retinite por CMV confirmada, no dia 120 do seguimento. Nenhum paciente teve testes de antigenemia positivos. Nenhuma correlação entre os ensaios linfoproliferativos e contagens de CD4+ foi observada. CONCLUSÃO: Descontinuação da terapia de manutenção para retinite por CMV é segura para aqueles pacientes com recuperação imune quantitativa após HAART.

Intravitreal foscarnet for cytomegalovirus retinitis in patients with AIDS.

To determine the visual outcome, progression, and complications of patients with acquired immuno-deficiency syndrome-related cytomegalovirus (CMV) retinitis treated with intravitrealfoscarnet (2.4 mg in 0.1 ml per injection), a retrospective study was carried out in 193 patients. Induction therapy consisted of two injections a week until the lesions were inactive. Maintenance therapy consisted of one injection a week until relapse, then re-induction was instituted. In 301 treated eyes, visual acuity remained stable in 184 (61%), improved in 16 (5%), and decreased in 101 (34%). Of these, 15 retinal detachments, 13 intravitreal hemorrhages, 3 endophthalmitis, and 2 cataract occurred. Median time of first progression was 15 weeks. Involvement of the fellow eye occurred in 35% of the patients during treatment of the first eye. Intravitreal foscarnet appeared to be a useful alternative treatment for patients intolerant or unaffordable to intravenous anti-CMV drugs, but the complications of this treatment should also be considered.

Effect of combination antiretroviral therapy on cytomegalovirus retinitis.

PURPOSE: To study the various changes in the course of cytomegalovirus (CMV) retinitis following combination antiretroviral treatment. METHODS: Combination antiretroviral treatment was given to 12 patients with active CMV retinitis following which all anti-CMV medications were discontinued once the CD4 cell counts were > 100/mm3 for 3 months. RESULTS: The median CD4 cell count increased from 36.5/mm3 (range, 3-74/mm3) at baseline to 175.5/mm3 (range, 97-410/mm3) at 3 months. No patient had reactivation of CMV retinitis or developed extraocular CMV infection during median follow-up of 16.7 months. In one patient with peripheral active CMV retinitis, the retinitis resolved completely and remained so throughout the follow-up period without specific anti-CMV treatment. Five (41.7%) patients had immune recovery vitritis. CONCLUSION: Patients receiving combination antiretroviral treatment following treatment for CMV retinitis have better control of CMV retinitis but immune recovery vitritis is a common sequelae. Reactivation of CMV retinitis is common in patients who discontinue combination antiretroviral treatment.

Treatment of cytomegalovirus retinitis with an intraocular sustained-release ganciclovir implant

The objective of this prospective study was to evaluate the efficacy and complications of the use of an intraocular sustained-release ganciclovir implant for the treatment of active cytomegalovirus (CMV) retinitis in AIDS patients. Thirty-nine eyes of 26 patients were submitted to ocular surgery. All patients underwent complete ocular examination before and after surgery. The surgical procedure was always done under local anesthesia using the same technique. The mean time for the surgical procedure was 20 min (range, 15 to 30 min). The average follow-up period was 3.7 months. Of all patient, only 4 presented recurrence of retinitis after 8, 8, 9 and 2 months, respectively. Three of them received a successful second implant. All 39 eyes of the 26 patients presented healing of retinitis as shown by clinical improvement evaluated by indirect binocular ophthalmoscopy and retinography. Retinitis healed within a period of 4 to 6 weeks in all patients, with clinical regression signs from the third week on. Six (15.4 percent) eyes developed retinal detachment. None of the patients developed CMV retinitis in the contralateral eye. The intraocular implant proved to be effective in controlling the progression of retinitis for a period of up to 8 months even in patients for whom systemic therapy with either ganciclovir or foscarnet or both had failed. The intraocular sustained-release ganciclovir implant proved to be a safe new procedure for the treatment of CMV retinitis, avoiding the systemic side effects caused by the intravenous medications and improving the quality of life of the patients.

Tratamiento de la retinitis por citomegalovirus en sujetos con síndrome de inmunodeficiencia adquirida / Treatment of cytomegalovirus retinitis in subjects with the acquired immunodeficiency syndrome

La afección por citomegalovirus en órganos como el ojo se ha constituido como una de las complicaciones más serias del síndrome de inmunodeficiencia adquirida (SIDA). Se manifiesta en 24 a 44 por ciento de sujetos en conteos celulares de T CD4 menores a 50 células/mm de los que el 85 por ciento desarrollan retinitis que evoluciona a destrucción retiniana y ceguera en caso de no instaurarse tratamiento específico.En la actualidad existen fármacos como ganciclovir (análogo nucleósido), foscarnet (análogo pirofosfato) y cidofovir (análogo nucleósido) que han mostrado su utilidad en el tratamiento de esta retinitis aunque sus reacciones adversas determinan limitaciones en su utilización. Además, fármacos como los inhibidores de proteasas, disminuyen la progresión del cuadro, mejorando la sobrevida, propiciando la recuperación inmune. Las terapias de tipo local también son efectivas aunque los riesgos relativos de su utilización en comparación con los beneficios aún deben de ser evaluados. En todo caso ante la confirmación de alteraciones oculares el fármaco utilizado para el tratamiento de esta retinitis debe de iniciarse rápidamente, asegurando así menor destrucción retiniana y una mayor preservación de la función visual por un periodo más largo de tiempo. Las alternativas terapéuticas antirretrovirales retardan el desarrollo de la retinitis por citomegalovirus dependiendo del periodo de evolución y la historia natural de este padecimiento.

Frequência da terapia de induçäo e reinduçäo do ganciclovir no tratamento da retinite por citomegalovírus / Frequency of induction and reinduction therapy of ganciclovir in the treatment of cytomegalovirus retinitis

Introduçäo: a retinite pelo citomegalovírus (CMV) é a infecçäo ocular mais frequente nos pacientes com a Síndrome de Imunodeficiência Adquirida (AIDS). O ganciclovir é utilizado como droga de escolha para o tratamento e controle de progressäo da doença. Objetivos: determinar a frequência do uso da terapia de induçäo e reinduçäo de ganciclovir no tratamento da retinite por CMV. Métodos: estudo retrospectivo de 1100 pacientes necessitaram de tratamento inicial com terapia de induçäo de ganciclovir (10mg/kg/dia por 21 dias) e outros 147 (59,8 por cento) estavam usando a terapia de manutençäo de 5mg/kg/dia. Tyrinta (12,2 por cento) pacientes necessitaram terapia de reinduçäo. Conclusöes: a taxa de recidiva dos nossos pacientes foi significativamente ..

Cytomegalovirus retinitis in AIDS patients: a clinical review

Cytomegalovirus (CMV) retinitis is an ocular condition previously seen in organ transplant recipients, patient on chemotherapy for malignancy, and in infants with congenital infections. As it present in immunocompromised, the AIDS patient has integrated this group of patients that can present with CMV retinitis. Moreover, it is the leading cause of opportunistic ocular infection in the AIDS patient, and the second most common ocular manifestation. As new drugs and modes of administration are studied that can effectively halt this progressively blinding condition, the awareness and recognition of CMV retinitis on AIDS patients has become increasingly important. This author will review the epidemiology, clinical presentation, and differential diagnosis of this condition. The current treatments being used and complications will also be discussed