Intravitreous and plasma concentrations of ganciclovir and foscarnet after intravenous therapy in patients with AIDS and cytomegalovirus retinitis

Jf, Arevalo; Gonzalez, Casimiro; Capparelli, EV; Kirsch, L. S.; Garcia, RF; Quiceno, JI; Connor, JD; Gambertoglio, John G.; Bergeron–Lynn, Germaine; Wr, Freeman

doi:10.1016/s0002-9394(14)70605-1

Cited by 10 publications

(13 citation statements)

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“…Time-dependent analyses were performed for the association of CMV load with CMV retinitis progression and with occurrence of resistant CMV, for the following reasons: (1) CMV retinitis progression occurs in nearly all patients treated with systemic anti-CMV therapy [1,26,42], because of the limited intraocular penetration of these drugs [43,44], even without the occurrence of resistance; and (2) regardless of whether a patient harbors a resistant virus, treatment regimens and CMV load may change over time [15,27]. Patient follow-up was divided into 3-month blocks centered on the collection of specimens for CMV culture and CMV load measurement.…”

Section: Patientsmentioning

confidence: 99%

Cytomegalovirus (CMV) Blood DNA Load, CMV Retinitis Progression, and Occurrence of Resistant CMV in Patients with CMV Retinitis

et al. 2005

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The amount of cytomegalovirus (CMV) DNA in the blood (CMV load) may be a marker for detection of resistant CMV.METHODS. A total of 165 patients with AIDS and CMV retinitis had CMV load measurements (plasma and leukocyte) and cultures performed every 3 months; these measurements were correlated with CMV resistance to antiviral drugs and CMV retinitis progression (from masked readings of retinal photographs).RESULTS. Detectable plasma and leukocyte CMV loads were associated with CMV retinitis progression (odds ratios [OR], 6.3; P<.0001 and OR, 6.6; P<.0001, respectively), phenotypic resistance (OR, 6.1; P<.0001 and OR, 23.4; P=.0002, respectively), and genotypic resistance (OR, 17.5; P<.0001 and OR, 51.6; P=.0004, respectively). The sensitivity, specificity, and positive and negative predictive values of plasma CMV loads were 0.47, 0.86, 0.36, and 0.91, respectively, for progression and 0.59, 0.81, 0.07, and 0.99, respectively, for resistance; those of leukocyte CMV loads were 0.52, 0.83, 0.35, and 0.91, respectively, for progression and 0.82, 0.78, 0.08, and 0.99, respectively, for resistance. A detectable plasma CMV load at the time of diagnosis of CMV retinitis was associated with mortality (median survival time, 13.6 vs. 29.7 months; P=.007).CONCLUSIONS. CMV load has limited clinical utility, because of its low positive predictive value. Its high negative predictive value for occurrence of resistant CMV suggests that it may have utility as a screening tool to exclude resistance.

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Section: Patientsmentioning

confidence: 99%

Cytomegalovirus (CMV) Blood DNA Load, CMV Retinitis Progression, and Occurrence of Resistant CMV in Patients with CMV Retinitis

et al. 2005

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“…We have previously shown that intravitreal levels of systemically administered antiviral compounds are low. 48 The exposure of the retina to low steady-state antiviral drug levels is likely to favor the selection of drug-resistant CMV populations within the eye. Additionally, in patients receiving systemic therapy for bilateral retinitis, it has been noted that clinical resistance to treatment may develop in one and not the other eye, which supports the notion that the development of resistance can be a local event.…”

Section: Commentmentioning

confidence: 99%

Clinical Failure of CMV Retinitis With Intravitreal Cidofovir Is Associated With Antiviral Resistance

Smith

Taşkintuna²,

Rahhal³

et al. 1998

Arch Ophthalmol

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To determine the incidence of clinical resistance to intraocular cidofovir injection for treatment of acquired immunodeficiency syndrome (AIDS)related cytomegalovirus (CMV) retinitis, and to identify virologic features associated with cidofovir treatment failure.Patients and Methods: Clinical resistance to intravitreal cidofovir was examined in 64 patients with CMV retinitis who received at least 1 injection of 20 µg of cidofovir. Histopathologic examination, culture, and polymerase chain reaction were used to detect CMV in ocular specimens. Antiviral resistance was assessed by plaque reduction assay and DNA sequencing.Results: Clinical resistance to intravitreal cidofovir injections was identified in 3 patients (5%) and was asso-ciated with prior oral ganciclovir or intravenous cidofovir use. Ganciclovir-and cidofovir-resistant CMV isolates were cultured from 2 patients and harbored resistanceassociated mutations in the UL97 and polymerase genes. Resistance mutations were also detected by direct analysis of vitreous. In 1 patient, different resistance mutations were identified in ocular vs extraocular CMV strains.

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“…Arevalo et al [62] evaluated intravitreous and plasma ganciclovir and foscarnet concentrations of 52 AIDS patients after intrave nous drug administration. High-pressure liquid chroma tography showed mean ganciclovir concentrations on in duction and maintenance therapy of 4.74 ± 1.49 \iM (n = 24) and 3.29 ± 1.84 \iM (n = 30), respectively.…”

Section: Studies Regarding Intravenous Ora! and Intraocular/implant mentioning

confidence: 99%

Treatment of Cytomegalovirus Diseases

Vogel

Scholz²,

Cinatl³

1997

Intervirology

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This review summarizes current strategies for the treatment of human cytomegalovirus (CMV) infection/diseases in high-risk patients such as transplant recipients and AIDS patients. Since the major drugs ganciclovir (Cytovene), foscarnet (Foscavir) and cidofovir (Vistide) are frequently associated with severe side effects and the formation of viral resistance, it should be endeavored to develop better strategies in anti-CMV treatment. Moreover, blocking of the viral replication does not always resolve the manifestations which are often linked with CMV-associated immunopathomechanisms. Thus, the efficacy of the available drugs is also discussed in the light of their ability to modulate inflammatory components of the cell-mediated immune system.

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Intravitreous and plasma concentrations of ganciclovir and foscarnet after intravenous therapy in patients with AIDS and cytomegalovirus retinitis

Cited by 10 publications

References 0 publications

Cytomegalovirus (CMV) Blood DNA Load, CMV Retinitis Progression, and Occurrence of Resistant CMV in Patients with CMV Retinitis

Cytomegalovirus (CMV) Blood DNA Load, CMV Retinitis Progression, and Occurrence of Resistant CMV in Patients with CMV Retinitis

Clinical Failure of CMV Retinitis With Intravitreal Cidofovir Is Associated With Antiviral Resistance

Treatment of Cytomegalovirus Diseases

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