Specific anti-CMV Therapy Research Articles

Active cytomegalovirus retinitis after the start of antiretroviral therapy

Patients with AIDS-related cytomegalovirus (CMV) retinitis receiving combined antiretroviral therapy (cART), but not specific anti-CMV therapy, consistently showed active retinitis for several months. Delayed diagnosis and treatment of CMV retinitis...

Impact of highly active antiretroviral therapy on cytomegalovirus viraemia, in the absence of specific anti-cytomegalovirus therapy

(1) to evaluate the effect of HAART on CMV viraemia in co-infected patients, in the absence of specific anti-CMV therapy; (2) to compare 2 molecular biology techniques for the detection and quantification of CMV-DNA in these patients. We present the preliminary data of an ongoing prospective research grant on newly diagnosed HIV seropositives, in a tertiary care hospital, during June 2006- June 2008. Clinical, virological (HIV and CMV viraemia) and immunological (CD4) screening was performed every 3 months. The CMV viraemia was performed by RoboGene Human Cytomegalovirus Quantification kit (aj Roboscreen). We retested all undetectable CMV viremia found in patients with CD4 <50/mmc, by CMV PCR kit (Qiagen Diagnostics). Both PCR reactions were performed on ABI Prism 7000 (Applied Biosystems). Up to date, our study has included 105 HIV-infected subjects, who were seropositive for anti-CMV IgG antibodies. Average follow-up was 18 months. CMV viraemia was found detectable in 21 cases at first visit and in other 5 at the second visit. 22 cases had CD4 <50/mmc, among which 14 had undetectable CMV viraemia. The results of both molecular biology techniques were widely the same. HAART was prescribed to 86% of the patients; all the patients having detectable CMV viraemia received HAART, but not any specific anti-CMV therapy. Under HAART, all the detectable CMV loads which were retested in time became undetectable at next visits, after a median of 16.5 weeks from the introduction of therapy. CMV viraemia detection was useful in early diagnosis of asymptomatic CMV infection. As opposed to transplant cases, molecular biology techniques for the detection and quantification of CMV-DNA in HIV-patients have not been standardized yet. In our study, the two kits RoboGene Human Cytomegalovirus (HCMV) Quantification kit (aj Roboscreen) and CMV PCR kit (Qiagen Diagnostics) were comparable. HAART made the reduction of CMV viral load, without any specific anti-CMV therapy. As in the case of other opportunistic infections, undetectable natural history of CMV infection seemed to have been improved by controlling HIV infection.

Characteristics of Untreated AIDS-related Cytomegalovirus Retinitis. I. Findings before the Era of Highly Active Antiretroviral Therapy (1988 to 1994)

To identify factors related to variations in the appearance of untreated AIDS-related cytomegalovirus (CMV) retinitis in severely immunodeficient individuals before the availability of highly active antiretroviral therapy (HAART) and to draw inferences regarding early events in the natural history of CMV retinitis based on clinical findings. Retrospective, observational case series. We evaluated a series of 100 adult patients with AIDS and newly diagnosed CMV retinitis before the HAART era who were not being treated with specific anti-CMV therapy. Demographic factors, ophthalmic findings, and the influence of drug therapy (zidovudine, acyclovir) on lesion characteristics were evaluated. Lesion border opacity was scored using a four-point scale of severity. Lesions could be categorized by type (fulminant/edematous or indolent/granular) in only 66% of eyes. Severe lesion border opacity (4+) was related to presence of zone 1 lesions (P = .032) and greater extent of disease (P = .004). Acyclovir use was associated with less severe opacity (P = .029) and less zone 1 involvement (P = .016). Early lesions were adjacent to vessels in 73% of eyes; the fovea was involved in 13% of eyes. Lesion location and drug use that affects virus activity may influence the severity of lesion border opacity, a measure that may be more useful than lesion type in future clinical studies of CMV retinitis. In contrast to earlier concepts, CMV retinitis does not seem to be a fovea-sparing disease. Findings in this study can serve as a reference for investigations into possible changes in CMV retinitis since the introduction of HAART.

Treatment of CMV Retinitis with Intravitreal Ganciclovir in the HAART Era

To describe the course and outcome of cytomegalovirus (CMV) retinitis among AIDS patients treated with intravitreal ganciclovir and systemic highly active antiretroviral therapy (HAART). The secondary objective was to compare the course of CMV retinitis between patients receiving HAART and those not receiving this treatment. A retrospective cohort design consisting of 21 eyes from 16 patients with AIDS and CMV retinitis consecutively enrolled between January 1996 and August 1999. All patients received intravitreal ganciclovir therapy, and half of the patients began HAART as well. Duration of intravitreal therapy and ensuing disease quiescence, as well as CD4+ T cell counts at diagnosis and at cessation of ganciclovir, were calculated. Secondly, instantaneous hazards for outcomes such as CMV retinitis progression, ocular complications and mortality were compared. Tertiary care centre in Ottawa, Ontario. Five of eight patients receiving HAART discontinued intravitreal ganciclovir after a mean treatment period of 428 days. During this period, their mean CD4+ count rose from 7.5 to 190microL. Subsequently, none of these patients experienced retinitis progression during follow-up periods lasting up to 820 days (mean of 617 days). Progression of CMV retinitis was 11.4 times more likely among those not receiving HAART (P=0.049). On initiating HAART, patients with CMV retinitis may enjoy significant recovery in CD4+ counts and sustained retinitis quiescence without specific anti-CMV therapy. Intravitreal ganciclovir injections seem well suited to offer effective CMV control during temporary periods of decreased CD4+ counts while awaiting HAART-mediated immune system reconstitution.

New issues in the management of patients with AIDS-related cytomegalovirus retinitis.

JAMA Discontinuation of Anticytomegalovirus Therapy in Patients With HIV Infection and Cytomegalovirus Retinitis Scott M. Whitcup, MD; Eric Fortin, MD; Anne S. Lindblad, PhD; Paul Griffiths, MD; Julia A. Metcalf, BA; Michael R. Robinson, MD; Jody Manischewitz, MS; Barbara Baird, RN; Cheryl Perry, RN; I. Michael Kidd, PhD; Tamara Vrabec, MD; Richard T. Davey, Jr, MD; Judith Falloon, MD; Robert E. Walker, MD; Joseph A. Kovacs, MD; H. Clifford Lane, MD; Robert B. Nussenblatt, MD; Janine Smith, MD; Henry Masur, MD; Michael A. Polis, MD Context Persons with cytomegalovirus (CMV) retinitis and acquired immunodeficiency syndrome (AIDS) have required lifelong anti-CMV therapy to prevent the progression of retinal disease and subsequent loss of vision. Objective To determine whether patients who were taking highly active antiretroviral therapy (HAART) and who had stable CMV retinitis could safely discontinue anti-CMV therapy without reactivation of their retinitis or increase in human immunodeficiency virus (HIV) viral load. Design Prospective nonrandomized interventional trial performed from July 1997 to August 1999. Setting Clinical Center of the National Institutes of Health, Bethesda, Md. Patients Fourteen patients with stable CMV retinitis and HIV infection and CD4 + cell counts higher than 0.15 × 10 9 /L and being treated with systemic anti-CMV medications and HAART. Interventions Discontinuation of specific anti-CMV therapy. Main Outcome Measures Reactivation of CMV retinitis, development of extraocular CMV infection, detection of CMV in blood and urine, HIV burden, immunologic function, quality of life, morbidity, and mortality. Results Twelve (89.7%) of 14 patients had evidence of immune recovery uveitis before anti-CMV drugs were discontinued. No patient had reactivation of CMV retinitis or development of extraocular CMV disease during mean follow-up of 16.4 months (range, 8.3-22.0 months) without anti-CMV therapy. Human immunodeficiency viral load remained stable following cessation of anti-CMV medications. Blood and urine assays for CMV were briefly positive in 9 patients but did not predict reactivation of CMV disease. Worsening immune recovery uveitis was associated with a substantial (>3 lines) vision loss in 3 patients. Conclusions Maintenance anti-CMV medications were safely stopped in those patients who had stable CMV retinitis and elevated CD4 + cell counts and who were taking HAART. The study demonstrates that immune recovery following potent antiretroviral therapy is effective in controlling a major opportunistic infection, even in patients with a history of severe immunosuppression. 1999;282:1633-1637.

Cytomegalovirus Retinitis in the Era of Highly Active Antiretroviral Therapy

A number of striking changes have occurred recently in the presentation and course of cytomegalovirus (CMV) retinitis in patients with acquired immunodeficiency syndrome (AIDS) who are receiving highly active antiretroviral therapy (HAART). Before the use of HAART, CMV retinitis was the most common intraocular infection in patients with AIDS, occurring in up to 40% of patients, typically when CD4+ cell counts have decreased to less than 0.10 x 10(9)/L. By studying CMV retinitis, clinicians can investigate whether the rejuvenated immune system that results from HAART can effectively control opportunistic infections in patients with AIDS. In some patients, retinitis has not progressed when specific anti-CMV therapy was discontinued, but a number of patients have developed substantial intraocular inflammation, which has resulted in decreased visual acuity. Anterior uveitis, cataract, vitritis, cystoid macular edema, epiretinal membrane, and disc edema may occur in patients with CMV retinitis who have experienced HAART-associated elevation in CD4+ cell counts. Since immune recovery uveitis does not occur in eyes without CMV retinitis, the ocular inflammation appears to be related to the CMV infection. Anti-CMV maintenance therapy likely can be safely discontinued in some patients with CMV retinitis if CD4+ cell counts are stable or increasing and have been higher than 0.10 x 10(9)/L for at least 3 months. Immune recovery in patients receiving HAART has been effective in controlling opportunistic infections, but it may also result in intraocular inflammation, which can have adverse effects on the eye.

Loss of cytomegalovirus (CMV) viraemia following highly active antiretroviral therapy in the absence of specific anti-CMV therapy.

To determine the effect of highly active antiretroviral therapy (HAART) on cytomegalovirus (CMV) viraemia and retinitis in patients at high risk of disease. Sixteen patients with CMV viraemia, but no evidence of end organ disease at the time of first receipt of HAART including a protease inhibitor, were studied. No patient had ever received specific anti-CMV therapy. CMV load in blood was measured using quantitative competitive PCR at baseline and for a median follow-up of 21 months. Regular ophthalmological screening for retinitis was conducted throughout the study period. All 16 patients became CMV negative by PCR following the commencement of HAART. CMV loads prior to treatment ranged from 2.0 x 10(3) to 4.1 x 10(6) copies/ml (median, 7.6 x 10(4) copies/ml). The median time to becoming PCR negative was 13.5 weeks (range, 5-40 weeks). Fourteen patients remained CMV negative throughout follow-up. CMV viraemia recurred in two patients; these individuals were indistinguishable with respect to either baseline parameters or response to antiretroviral therapy. None of the 16 patients developed CMV retinitis. HAART including a protease inhibitor can result in the complete suppression of CMV viraemia, an effect not previously observed in HIV-infected patients in the absence of specific anti-CMV therapy. This response correlated with protection against CMV retinitis in a group of patients at high risk of development of disease. These results help to explain why the natural history of CMV disease has altered since the introduction of such therapeutic regimens.

New strategies for the management of AIDS-related CMV retinitis in the era of potent antiretroviral therapy

The management of AIDS-related cytomegalovirus (CMV) retinitis is evolving because of newly available anti-CMV drugs and because of the effect of potent antiretroviral therapy. New management issues are related to the improved immune function that occurs with antiretroviral drug use and to associated increases in patient survival. Patients can be categorized on the basis of their history of exposure to antiretroviral drugs and to their immune status; these factors will influence choices between treatment options. In some patients with improved immune function, specific anti-CMV therapy can be withdrawn altogether without reactivation of infection. There are curently many treatment options available for those who need specific anti-CMV treatment: ganciclovir via various routes (intravenous (IV), oral, intraocular implant); IV foscarnet; IV cidofovir; intravitreous fomivirsen; or a combination of these agents. Previous short-term therapies are being adapted to the long-term management of what has become a chronic disease. Management strategies also involve appropriate monitoring for the recurrence of disease activity and the development of complications, such as retinal detachment or immune recovery uveitis. This chapter provides an overview of new treatment strategies that will assist clinicians in choosing between treatment options.

Diagnosing and treating cytomegalovirus pneumonia in patients with AIDS.

Because cytomegalovirus (CMV) can be isolated from pulmonary secretions of human immunodeficiency virus (HIV)-infected patients without causing disease, its clinical significance as a cause of pneumonia in this patient population is frequently questioned. In a 22-month period, CMV pneumonia was diagnosed in 17 (8%) of 210 HIV-infected patients who underwent lung biopsy on the basis of microbiological and histologic criteria. The clinical presentations of these patients were nonspecific, including fever (100% of patients), shortness of breath (71%), cough (76%), and Pao2 of < 75 mm Hg (88%). A high correlation in the degree of viral burden in lung biopsy specimens was demonstrated by histologic examination, immunohistochemical analysis, and in situ hybridization. No other pulmonary pathogens were identified for nine patients, whereas other possible causes of pneumonia were present in eight: 11 patients had evidence of extrapulmonary CMV disease at presentation. Most patients initially responded to specific anti-CMV therapy; the overall mean survival +/- SD was 3.1 +/- 2.5 months. CMV should be considered as a possible cause of pneumonia in patients with advanced AIDS especially if CMV infection is documented at other sites.