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AIDS-related cytomegalovirus neurologic disease

AIDS-related cytomegalovirus neurologic disease
Literature review current through: Jan 2024.
This topic last updated: Aug 05, 2022.

INTRODUCTION — Cytomegalovirus (CMV) neurologic disease is an uncommon serious complication of acquired immunodeficiency syndrome (AIDS), which can cause paralysis or rapidly fatal encephalitis. Prior to the availability of potent antiretroviral therapy (ART), CMV neurologic disease occurred in up to 2 percent of patients with AIDS [1], primarily in those with a CD4 count <50 cells/microL. However, the incidence of CMV neurologic disease has decreased since ART became available [2].

This topic will discuss AIDS-related CMV neurologic disease. Discussions of other CMV-related diseases in patients with human immunodeficiency virus (HIV) are found elsewhere. (See "Pathogenesis, clinical manifestations, and diagnosis of AIDS-related cytomegalovirus retinitis" and "Treatment of AIDS-related cytomegalovirus retinitis" and "AIDS-related cytomegalovirus gastrointestinal disease".)

PATHOGENESIS — It is hypothesized that cytomegalovirus (CMV) end-organ disease results from the hematogenous spread of CMV. The presence of CMV in blood (as measured by culture, CMV deoxyribonucleic acid (DNA) amplification, or antigen detection) is a risk factor for the development of CMV disease in patients with AIDS [3]. However, patients with viremia (eg, those with a positive blood CMV DNA test result) do not necessarily have invasive disease. (See 'Evaluation' below.)

Impaired CD4 cell function or number is the key immune deficit that permits uncontrolled CMV replication. Studies in transplant recipients and patients with AIDS indicate that CD4-dependent CMV-specific cytotoxic T lymphocyte activity is critical for preventing CMV replication and end-organ disease [4-6]. Although most cases of CMV disease occur in patients with a CD4 cell count <50 cells/microL, patients may be predisposed before such severe CD4 cell depletion occurs. As an example, in a longitudinal study, patients with AIDS who subsequently developed CMV disease had lower T-cell proliferative responses to CMV, both early and late, compared to patients who did not develop disease [7]. Genetic factors may also contribute to this predisposition, since low responses to CMV were more common in those with HLA-B44 and HLA-DR7.

Viral factors may also impact disease. CMV strains in the cerebrospinal fluid of patients with HIV with encephalitis may differ significantly from those strains present in the general population. A phylogenetic analysis suggests possible viral recombination events that may have an effect on neurovirulence [8].

Pathology — CMV neurologic disease can involve the brain, spinal cord, dorsal column nerve roots, or peripheral nerves. CMV inclusions have been identified in astrocytes, neurons, oligodendrocytes, and capillary endothelia of neural tissue. In the brain, CMV disease is characterized histologically by one of three patterns:

Microglial nodules that are dense aggregates of macrophages and/or rod cells occurring in gray matter more often than white matter

Focal parenchymal necrosis

Ventriculoencephalitis with focal or diffuse destruction of the ependymal lining and periventricular tissue [9]

In the spinal cord, nerve roots, and peripheral nerves, CMV disease can cause subpial necrosis, axonal destruction, myelin degeneration, and a focal, polymorphonuclear necrotizing vasculitis of epineural arteries [10,11].

NATURAL HISTORY — Prior to the introduction of potent antiretroviral therapy (ART), the median survival of patients with cytomegalovirus (CMV) neurologic disease was less than three months in several small series [12]. However, ART has altered the natural history of CMV neurologic disease, and long-term survival has been reported in some patients, even if patients initiate ART after being diagnosed with CMV disease [13]. (See 'When to initiate antiretroviral therapy' below and "Selecting antiretroviral regimens for treatment-naïve persons with HIV-1: General approach".)

CLINICAL MANIFESTATIONS — Neurologic disease resulting from cytomegalovirus (CMV) occurs primarily in profoundly immunocompromised subjects. As an example, in a systematic review of 676 patients with CMV encephalitis, 85 percent had AIDS, 12 percent had other causes of immunosuppression, and only 3 percent were immunocompetent [9]. Among individuals with AIDS, CMV neurologic disease typically presents in patients with a CD4 count <50 cells/microL; the signs and symptoms depend upon the anatomic location. There have also been several cases of immune reconstitution inflammatory syndromes (IRIS) reported after initiation of potent ART, where the clinical manifestation was encephalitis and the putative antigenic stimulus was central nervous system (CNS) CMV infection [14,15]. (See "Immune reconstitution inflammatory syndrome".)

Encephalitis — Patients with CMV encephalitis tend to present with altered mental status that is difficult to distinguish clinically from the cognitive changes caused by HIV itself [9]. However, delirium, confusion, and focal neurologic abnormalities are more commonly associated with CMV-related encephalitis than with HIV-related cognitive changes [12]. (See "HIV-associated neurocognitive disorders: Epidemiology, clinical manifestations, and diagnosis", section on 'HIV-associated dementia'.)

Patients with CMV ventriculoencephalitis present with a more acute onset of lethargy and confusion, often accompanied by cranial nerve involvement. Computerized tomography scan or magnetic resonance imaging of the brain may be unremarkable but often shows periventricular enhancement in this setting. (See 'Diagnosis' below.)

Myelitis — Patients with CMV myelitis present with lower extremity weakness and hyperactive reflexes on neurologic examination. (See "Disorders affecting the spinal cord", section on 'Acute viral myelitis'.)

Polyradiculopathy — Patients with CMV polyradiculopathy present with decreased lower extremity strength, decreased or absent reflexes, and in some cases, urinary retention. The onset of symptoms usually occurs over a period of days to weeks. (See "Polyradiculopathy: Spinal stenosis, infectious, carcinomatous, and inflammatory nerve root syndromes", section on 'Polyradiculopathy in HIV and AIDS'.)

Peripheral neuropathy — Patients with CMV peripheral nerve disease usually present with the syndrome of mononeuritis multiplex, consisting of multifocal or asymmetric sensory and motor deficits in the distribution of major peripheral or cranial nerves (including the laryngeal nerves) [16].

EVALUATION — Cytomegalovirus (CMV)-related neurologic disease should be considered in patients with AIDS who present with neurologic signs and symptoms (see 'Clinical manifestations' above), especially if their CD4 count is <50 cells/microL and/or they have CMV in another site.

The evaluation of a patient suspected of having CMV neurologic disease depends upon the clinical presentation. The evaluation of patients with peripheral neuropathy is presented elsewhere. (See "Overview of polyneuropathy".).

For others, the evaluation typically includes:

Magnetic resonance imaging or contrast computerized tomography.

Evaluation of the cerebrospinal fluid for cell count, protein, and CMV DNA or antigen, if there are no contraindications to lumbar puncture. (See "Approach to the patient with HIV and central nervous system lesions".)

Blood assays to detect CMV DNA or antigen have poor sensitivity and specificity for all forms of AIDS-related CMV end-organ disease and are not useful for diagnosis [17].

Patients with extraocular CMV disease often have prior or concurrent CMV retinitis. Thus, individuals diagnosed with CMV neurologic disease, who are not already known to have retinitis, should undergo formal ophthalmologic screening for retinitis. Exams should be repeated at six-month intervals until the patient's absolute CD4 count has been restored to ≥100 cells/microL on ART. (See "Pathogenesis, clinical manifestations, and diagnosis of AIDS-related cytomegalovirus retinitis".)

DIAGNOSIS — The diagnosis of cytomegalovirus (CMV)-related disease is based upon the clinical presentation, and is typically supported by findings on magnetic resonance imaging (MRI) or computerized tomography (CT), and/or documenting the presence of CMV infection in the cerebrospinal fluid (CSF) through polymerase chain reaction (PCR) assays or antigen testing. (See 'Evaluation' above.)

Encephalitis — The presence of CMV encephalitis should be suspected in patients with advanced HIV disease who have a progressive change in mental status, delirium, rapidly progressive cognitive impairment, and/or signs and symptoms of brainstem injury. (See 'Encephalitis' above.)

An MRI or contrast CT scan must be performed to exclude toxoplasmosis, lymphoma, progressive multifocal leukoencephalopathy, or other intracranial processes. Evidence of periventricular inflammation or meningeal enhancement helps support the diagnosis of CMV encephalitis but is not specific for the disease. In addition, case reports have demonstrated that MRI is not always sensitive to the presence of CMV encephalitis, even when it is quite severe. [18].

CMV DNA (eg, by PCR) or CMV antigen in the CSF is highly sensitive and specific for CMV neurologic disease involving the brain [19-21]. In one study of 13 patients with autopsy-proven CMV infection of the brain (eg, ventriculoencephalitis), 12 had CMV DNA in the CSF compared to none of the 11 without evidence of CMV infection [20].

Myelitis — The presence of CMV myelitis should be suspected in patients with advanced HIV disease who have progressive lower extremity weakness and hyperactive reflexes on neurologic examination. (See 'Myelitis' above.)

An MRI or contrast CT scan of the spinal cord (or myelogram) should be performed to exclude mass lesions. Enhancement of the cord supports a presumptive diagnosis of CMV myelitis. A positive test for CMV DNA in the CSF also provides evidence of this diagnosis; however, cerebrospinal fluid analysis may be unremarkable.

Radiculomyelopathy — The presence of CMV radiculomyelopathy should be suspected in patients who have progressive lower extremity weakness and decreased or absent reflexes on neurologic examination. (See 'Polyradiculopathy' above.)

An MRI or contrast CT scan of the spinal cord (or myelogram) should be performed to exclude mass lesions. Nerve root thickening, if present, supports the diagnosis of CMV radiculomyelopathy. A lumbar puncture should be done for CSF analysis. A CSF polymorphonuclear pleocytosis with a negative CSF bacterial culture is evidence for CMV radiculomyelopathy in a patient with AIDS who has a CD4 cell count <50 cells/microL. A positive test for CMV DNA in the CSF strongly supports this diagnosis.

Peripheral neuropathy — The diagnosis of CMV mononeuritis multiplex should be suspected in patients who have multifocal or asymmetric sensory and motor deficits in the distribution of major peripheral or cranial nerves (including the laryngeal nerves). (See 'Peripheral neuropathy' above.).

Biopsy of an involved peripheral nerve or a positive CSF CMV DNA result can confirm the diagnosis. A more detailed discussion on the evaluation of patients with polyneuropathy is found elsewhere. (See "Overview of polyneuropathy".)

TREATMENT

Approach — Our approach to the initial or induction phase of treatment for patients with cytomegalovirus (CMV) neurologic disease depends upon the degree of neurologic impairment as well as the patient’s ability to tolerate the anti-CMV regimen.

For induction treatment of patients with severe CMV neurologic disease (eg, CMV encephalitis in a patient who is obtunded), we suggest dual therapy with intravenous (IV) ganciclovir and foscarnet. (See 'Severe disease' below.)

For individuals with severe disease who cannot tolerate dual induction therapy, we suggest monotherapy with ganciclovir or foscarnet, depending upon which drug is better tolerated. (See 'Adverse reactions' below and 'Severe disease' below.)

For the induction treatment of patients with mild disease (eg, a patient with CMV polyradiculopathy or mononeuritis multiplex who has mild motor deficits), we suggest monotherapy with oral valganciclovir. (See 'Mild disease' below.)

Cidofovir is an alternative therapy for the treatment of CMV neurologic disease in patients who cannot tolerate any of the other options (ie, ganciclovir, valganciclovir, or foscarnet). (See 'Cidofovir' below.)

Patients should initiate antiretroviral medications approximately 14 days after anti-CMV therapy has started since immune recovery is an important adjunct to antiviral therapy in the treatment of CMV neurologic disease. A discussion of when to start antiretroviral therapy (ART) is found below. (See 'When to initiate antiretroviral therapy' below.)

After the induction anti-CMV treatment regimen has been completed, patients should be transitioned to a maintenance regimen until the CD4 count has increased to ≥100 cells/microL for at least six months. Valganciclovir is the typical agent for maintenance therapy. (See 'Duration of treatment' below.)

Ganciclovir and foscarnet — We administer IV ganciclovir (or valganciclovir if the patient can tolerate oral therapy) and/or foscarnet for the treatment of CMV neurologic disease. The use of combination versus monotherapy depends upon the intensity of neurologic impairment and the risk of complications from these agents. (See 'Adverse reactions' below.)

Severe disease — For patients with severe disease (eg, CMV encephalitis in a patient who is obtunded), we suggest dual therapy with both IV ganciclovir and foscarnet. The use of dual therapy for patients with severe CMV neurologic disease is based upon findings from a randomized trial that found patients with relapsed CMV retinitis who received combined ganciclovir and foscarnet had better outcomes compared with those who received monotherapy with either of these agents [22]. Although there have been no prospective randomized trials of treatment for CMV neurologic disease, dual therapy is used given the poor outcomes seen in many patients with severe CMV neurologic disease.

Several dual therapy regimens can be used to treat severe CMV neurologic disease. The choice of which regimen to use depends upon the risk of adverse reactions (see 'Adverse reactions' below):

IV ganciclovir (5 mg/kg every 12 hours) plus foscarnet (90 mg/kg per day)

OR

IV ganciclovir (5 mg/kg per day) plus foscarnet (90 mg/kg every 12 hours)

OR

IV ganciclovir (5 mg/kg every 12 hours) plus foscarnet (90 mg/kg every 12 hours) [17]

We administer one of these induction treatment regimens until symptomatic improvement; thereafter, chronic maintenance therapy should be provided until ART has been optimized to achieve viral suppression and adequate immune reconstitution. (See 'When to initiate antiretroviral therapy' below and 'Duration of treatment' below.)

Monotherapy should be used for those with severe disease who are unable to tolerate dual therapy, monotherapy with either agent can be used:

IV Ganciclovir (5 mg/kg every 12 hours)

OR

Foscarnet (90 mg/kg every 12 hours)

Dose modifications for renal impairment may be needed; detailed dosing recommendations are available in the individual drug information monographs included within UpToDate and the individual topic reviews. (See "Ganciclovir and valganciclovir: An overview" and "Foscarnet: An overview".)

If the patient is able to take oral medications, oral valganciclovir can be used instead of IV ganciclovir. Pharmacokinetically, oral valganciclovir at a dose of 900 mg is equivalent to IV ganciclovir at a dose of 5 mg/kg. Valganciclovir is the preferred drug for CMV end-organ disease because of its good bioavailability, lower cost compared with IV ganciclovir, and lack of complications related to infusional therapy. Although oral valganciclovir has only been tested in patients with CMV retinitis [23], it is likely to have similar efficacy to IV ganciclovir in patients with CMV neurologic disease. (See "Ganciclovir and valganciclovir: An overview".)

Mild disease — For individuals with mild CMV neurologic disease (eg, a patient with CMV polyradiculopathy or mononeuritis multiplex who has mild motor deficits), we suggest monotherapy rather than dual therapy. For such patients who are able to take oral medications, we initiate oral valganciclovir 900 mg twice daily. For individuals who are unable to take oral medications, intravenous ganciclovir (5 mg /kg every 12 hours) or foscarnet (90 mg/kg every 12 hours) can be used.

Adverse reactions — Ganciclovir and foscarnet are associated with a range of side effects that include:

Ganciclovir — Neutropenia and thrombocytopenia have been the main toxicities of chronic ganciclovir therapy in patients with AIDS and have been dose-limiting in 16 and 5 percent of patients, respectively. Ganciclovir-induced severe neutropenia usually can be reversed by the administration of granulocyte-colony stimulating factor [24]. (See "Ganciclovir and valganciclovir: An overview".)

Foscarnet — Reversible increases in serum creatinine (due to acute tubular necrosis) and symptoms of hypocalcemia during drug infusions (caused by transient chelation of serum ionized calcium which can fall by 0.7 to 1.1 mg/dL) are the most serious toxicities of foscarnet and have been dose-limiting in approximately 20 percent of patients [25,26]. Renal toxicity appears to be reduced by concomitant saline administration. Foscarnet can also cause hypomagnesemia, hypokalemia, and phosphate abnormalities, and rarely genital ulcers. (See "Foscarnet: An overview", section on 'Toxicity'.)

Cidofovir — Cidofovir is an alternative therapy for the treatment of CMV disease in patients who cannot tolerate any of the other options (ie, ganciclovir, valganciclovir, or foscarnet). Although no controlled trials have evaluated cidofovir for the treatment of CMV neurologic disease, it has been used to treat CMV retinitis (see "Treatment of AIDS-related cytomegalovirus retinitis"). However, the use of cidofovir is limited by its serious, irreversible nephrotoxicity that occurs via dose-dependent proximal tubular cell injury. Because of this toxicity, ganciclovir or foscarnet monotherapy with twice-daily dosing would be preferable to using cidofovir. (See 'Ganciclovir and foscarnet' above.).

Cidofovir is contraindicated in patients with a creatinine >1.5 mg/dL, an estimated glomerular filtration rate ≤55 mL/minute/1.73m2, or a urine protein ≥100 mg/dL. In addition, this agent should be avoided in patients with a sulfa allergy because of cross hypersensitivity with probenecid [17] (see 'Dosing of cidofovir' below). A more detailed discussion of cidofovir is found elsewhere. (See "Cidofovir: An overview".)

Dosing of cidofovir — Cidofovir is administered as 5 mg/kg per week intravenous infusion for two weeks, then 5 mg/kg every other week. Saline hydration and high-dose probenecid therapy (which can block cidofovir uptake by proximal renal tubular cells) should be given concomitantly with cidofovir to reduce the risk of serious renal injury [27,28]. Oral probenecid should be administered as 2 grams three hours before the infusion and 1 gram at both two and eight hours after the infusion. Detailed dosing recommendations are available in the cidofovir drug information monograph included within UpToDate.

Toxicity related to cidofovir — Nephrotoxicity or probenecid intolerance (eg, fever, nausea, vomiting, rash) have been treatment-limiting in approximately one-third to one-half of patients receiving cidofovir. The initial manifestations of renal toxicity are proteinuria and increased serum creatinine concentrations; with continued treatment, some patients develop a life-threatening Fanconi-like syndrome and renal failure. The exact incidence of nephrotoxicity is not known. In one series of 38 patients treated with either low- or high-dose cidofovir (3 and 5 mg/kg at two week intervals, respectively) for six to nine months, 10 developed an elevated serum creatinine concentration to 1.5 mg/dL or greater; and four (two in each group) had persistent elevations in this range [28].

In an attempt to prevent progressive renal injury, dipstick analysis of the urine for protein and measurement of urinary protein excretion (estimated from a random urine total protein-to-creatinine ratio) and the serum creatinine concentration should be performed immediately before each cidofovir dose (see "Assessment of urinary protein excretion and evaluation of isolated non-nephrotic proteinuria in adults"). The drug should be discontinued if the urine protein is 3+ or more, urine protein excretion increases significantly, or the serum creatinine rises by more than 0.5 mg/dL (44 micromol/L) over baseline. If the serum creatinine rises by 0.3 to 0.4 mg/dL (26.5 to 35 micromol/L) over baseline, the cidofovir dose should be reduced to 3 mg/kg [29]. Other nephrotoxic drugs must be avoided when using cidofovir. With this management strategy, survival in cidofovir treatment trials has been similar to that reported in other trials of therapy for CMV retinitis.

Other adverse events related to cidofovir include neutropenia, peripheral neuropathy, and alopecia. In addition, hypotony (abnormally low intraocular pressure) and anterior or posterior uveitis have been seen in individuals with CMV retinitis. In patients receiving protease inhibitor therapy, the risk of hypotony or uveitis may be as high as 25 percent [30].

Option for patients who fail or are intolerant of the above regimens — For patients who have either clinical or virologic resistance or intolerance to the agents mentioned above, maribavir is an alternative option. Maribavir is a CMV UL97 gene product inhibitor that is used for treatment of refractory CMV infection in solid organ transplant and hematopoietic stem cell transplantation (HSCT) recipients. Clinical and virologic improvement has been reported in transplant populations [31], and virologic improvement was reported in a phase 1 study of patients with advanced HIV disease, who had asymptomatic CMV shedding [32]. While there are no reports to date of maribavir treatment for AIDS-related CMV end-organ disease, the drug is orally bioavailable and relatively well tolerated. (See "Clinical manifestations, diagnosis, and management of cytomegalovirus disease in kidney transplant patients" and "Clinical manifestations, diagnosis, and treatment of cytomegalovirus infection in lung transplant recipients".)

Letermovir should not be used for the treatment of CMV end-organ disease. Letermovir is a CMV viral terminase complex inhibitor that is approved only for prophylaxis of CMV disease in allogeneic HSCT recipients. Though letermovir may eventually have a role in the treatment of CMV viremia in solid organ transplant recipients, its use in a few cases of CMV end-organ disease has not clearly provided benefit to the patient. In addition, letermovir can have problematic drug interactions with several non-nucleoside reverse transcriptase and protease inhibitor antiretroviral drugs used for HIV treatment, as well as all rifamycins used to treat tuberculosis. (See "Prevention of viral infections in hematopoietic cell transplant recipients".)

Duration of treatment — Induction therapy with ganciclovir and/or foscarnet should be continued until there is significant improvement in the patient’s neurologic symptoms, which typically occurs after several weeks of treatment [33]. (See 'Ganciclovir and foscarnet' above.)

After the patient has improved and ART has been initiated (see 'When to initiate antiretroviral therapy' below), anti-CMV treatment can be simplified to a maintenance regimen such valganciclovir monotherapy 900 mg/day. We suggest that valganciclovir be continued until the patient’s viral load is suppressed and the CD4 count has increased to ≥100 cells/microL for at least six months. This approach is based upon observational studies regarding the duration of maintenance therapy for patients with CMV retinitis [34-37]. (See "Treatment of AIDS-related cytomegalovirus retinitis", section on 'Discontinuing maintenance therapy'.)

If a patient is receiving foscarnet or cidofovir as induction therapy because they could not tolerate dose-related ganciclovir toxicity (eg, severe neutropenia or thrombocytopenia which resolved on discontinuing the drug or reducing the dose), they should be rechallenged with oral valganciclovir for maintenance therapy, assuming there were no severe complications related to ganciclovir that may not have been dose related (eg, hypersensitivity reaction, refractory bone marrow suppression, nephrotoxicity). If oral valganciclovir is not tolerated, patients receiving foscarnet should transition back to maintenance doses of foscarnet (90 to 120 mg/kg/day as a single infusion); individuals receiving cidofovir should continue therapy every other week as long as there is no evidence of nephrotoxicity.

When to initiate antiretroviral therapy — Potent antiretroviral therapy (ART) results in immune recovery and is an important adjunct in the treatment of opportunistic infections, including those with CMV neurologic disease. However, ART can produce an immune reconstitution inflammatory syndrome (IRIS), and rare cases of severe or fatal IRIS encephalitis have been attributed to CMV infection of the central nervous system. (See "Immune reconstitution inflammatory syndrome".).

For most patients with CMV neurologic disease, we suggest that ART be initiated 14 days after anti-CMV therapy has been started [17]. However, in some patients, the approach must be individualized. As an example, we delay ART longer if the patient has progressive neurologic deficits or uncontrollable seizures. For such patients, the risk of a worsening neurologic status secondary to possible IRIS must be weighed against the benefit of immune recovery.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Opportunistic infections in adults with HIV".)

SUMMARY AND RECOMMENDATIONS

Cytomegalovirus (CMV) neurologic disease is an uncommon serious complication of AIDS, which can cause paralysis or rapidly fatal encephalitis. Prior to the availability of potent antiretroviral therapy (ART), CMV neurologic disease occurred in up to 2 percent of patients with AIDS, primarily in those with a CD4 count <50 cells/microL. However, the incidence of CMV neurologic disease has decreased since ART became available. (See 'Introduction' above.)

Studies in transplant recipients and patients with AIDS indicate that CD4-dependent, CMV-specific cytotoxic T lymphocyte activity is critical for preventing CMV replication and end-organ disease, and that impaired CD4 cell function or number is the key immune deficit that permits uncontrolled CMV replication. (See 'Pathogenesis' above.)

The symptoms of CMV neurologic disease are determined by the anatomic location. Patients with CMV encephalitis tend to present with delirium while patients with CMV myelitis or polyradiculopathy may present with lower extremity weakness. (See 'Clinical manifestations' above.)

The diagnosis of CMV-related neurologic disease is based upon the clinical presentation, and is typically supported by findings on magnetic resonance imaging or computerized tomography and/or documenting the presence of CMV infection in the cerebrospinal fluid through polymerase chain reaction (PCR) assays or antigen testing. Blood assays to detect CMV DNA or antigen have poor sensitivity and specificity for all forms of AIDS-related CMV end-organ disease and are not useful for diagnosis. (See 'Evaluation' above and 'Diagnosis' above.)

The approach to treatment depends upon the degree of neurologic impairment and the risk of complications from the individual agents. For the initial treatment of patients with severe CMV neurologic disease, we suggest dual therapy with intravenous (IV) ganciclovir (or oral valganciclovir if the patient can tolerate oral therapy) and foscarnet rather than monotherapy with either agent (Grade 2C). (See 'Approach' above and 'Severe disease' above.)

For the initial treatment of individuals with mild disease, we suggest monotherapy with oral valganciclovir rather than intravenous foscarnet (Grade 2C). (See 'Approach' above and 'Mild disease' above.)

For patients with severe disease who cannot tolerate dual therapy with ganciclovir and foscarnet, we suggest monotherapy with twice-daily dosing of either agent rather than using the alternative agent cidofovir (Grade 2C). Although cidofovir may be effective for the treatment of CMV neurologic disease, its use is limited by serious, irreversible nephrotoxicity that occurs via dose-dependent proximal tubular cell injury. However, if an individual cannot take ganciclovir, valganciclovir, or foscarnet, cidofovir can be used. (See 'Severe disease' above and 'Cidofovir' above.)

For individuals who are not receiving ART, we suggest that ART be initiated 14 days after anti-CMV therapy has been started, rather than concurrently with anti-CMV therapy (Grade 2C). Rare cases of severe or fatal immune reconstitution inflammatory syndromes have been attributed to CMV infection of the central nervous system. For certain patients, we may delay ART even longer. (See 'When to initiate antiretroviral therapy' above.)’

After the patient has improved and ART has been initiated, anti-CMV treatment can be simplified to valganciclovir monotherapy (900 mg daily). We suggest that valganciclovir be continued until the patient’s viral load is suppressed and the CD4 count has increased to ≥100 cells/microL for at least six months (Grade 2C). (See 'Duration of treatment' above.)

ACKNOWLEDGMENT — UpToDate gratefully acknowledges John G Bartlett, MD (deceased), who contributed as Section Editor on earlier versions of this topic and was a founding Editor-in-Chief for UpToDate in Infectious Diseases.

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Topic 3750 Version 33.0

References

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