May have some in vitro and in vivo activity against CMV, but not indicated treatment since more active drugs now available.
Second-tier choice; probably effective, though renal toxicity and lack of data regarding CSF penetration preclude routine consideration.
Alternative choice for induction, though significant renal dysfunction will preclude use. Intermittent shortages may complicate use.
Favored agent for induction therapy, although patients with severe hematological problems despite transfusions/G-CSF etc. may do better with foscarnet.
Would not use for induction therapy due to multiple treatment failures in non-retinitis CMV infection. Not studied for CNS disease, but probably effective as oral maintenance therapy given drug bioavailability means acceptable ganciclovir levels.
Comment: CMV section last updated in 2015. The guideline gives moderately weighted recommendations for combination therapy at outset, but also acknowledges significant toxicities with this approach and limited evidence. An update said to be in progress (2019).
Comment: Authors use guideline-recommended treatment; however, emphasize the selection of ART drugs which higher CSF penetration given that distinguishing between HIV-induced encephalopathy and CMV encephalitis may be difficult.
Comment: A study from Ghana found that among HIV-seronegative blood donors, the seroprevalence of CMV was 77.6% and among HIV/AIDS patients was 59.2%. CMV (along with HHV-8 and EBV) are endemic in this region.
Comment: Interesting report from Cuba where ART was only used starting in 2001. Central lab analyzing CSF from HIV+ pts found CMV (44%), EBV (28%), and dual herpesvirus infections (16%) infections as the most common important agents identified. The use of ART, not surprisingly, correlated with lessened mortality.
Comment: Uses Cinque 1998 and Anduze-Faris 2000 to primarily guide recommendations.
Comment: The author suggests reserving foscarnet only for ganciclovir-resistant cases due to nephrotoxicity concerns or ganciclovir intolerance.
Comment: Study documents prevalence of HIV -associated dementia and polyneuropathy as significantly lower in 1997-8 (p=0.02), with the incidence of Toxoplasma encephalitis, decreased from 5.7% in 1995-6 to 2.2% in 1997-8 (p=0.015). However, because of small numbers, authors could reach no such similar conclusions regarding CMV CNS infection.
Comment: Pre-HAART open-label European study examining combination therapy with ganciclovir and foscarnet in 31 pts. with acute CMV encephalitis (CMVe) (n = 17) or CMV myelitis (CMVm) (n = 14). Induction therapy = "foscarnet" 90 mg/kg + ganciclovir 5 mg/kg twice-daily followed by maintenance dosing. Improvement or stabilization achieved in 74% (23/31 pts). Among 23 pts. on maintenance, CMV progressed in 10 (first relapse of 126 days; range 64-264 days). Median survival time 3 mos.
Comment: The document serves as the basis for suggested therapies mainly from the pre-ART era. Though little data other than case series exist for neurological CMV disease, extrapolation from CMV retinitis and GI studies not unreasonable given excellent penetration of both ganciclovir (24-67% of serum level) and foscarnet (13-68%) into the CSF.
Comment: Authors review data from literature and trials demonstrating that virus isolation or antigen detection in CSF not useful for HIV-related CMV encephalitis. Utility of CMV CSF-PCR appears to be the gold standard short of brain Bx: sensitivities 62-100% with 89-100% specificity.
Comment: Autopsy series with proven CNS CMV found 12/13 had positive CSF CMV PCR while none of the control patients positive. Higher log CSF PCR correlated with findings of more severe disease, suggesting that quantitative studies could be useful correlates of infection extant.
Comment: In this series, typical presentation is the subacute onset of leg weakness, numbness progressing to paraparesis or paraplegia. Bladder dysfunction is common. Authors note that improvement within 2-3 wks is typical for radiculopathy, but may take mos.
Comment: An older study examining literature, including autopsy series suggesting that silent CMV infection of the brain very common in those who die of HIV (~33%) but only a few have clinically suspected neurological disease antemortem (2%).
Comment: A review of 13 pts Dx’d between 2004-2008 found that only 4 (31%) were on ART but 8 patients (62%) had CMV neurological disease as presenting OI. In this group, most presented with diffuse encephalitis (7, 62%), then polyradiculopathy (7), rhomboencephalitis (1), and ventriculo-encephalitis, although some presentations included multiple presentations types. The mean CD4 count was 13.and overall mortality was 38%. A variety of treatment regimens used, but no conclusions could be reached regarding their use. Similar to the pre-ART era, 30% of pts present with concomitant CMV retinitis. Authors recommend routine opthamological exams in all patients with CMV neurological disease. No pts experienced IRIS.
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