Download TREATMENT of CMV retinitis in resource

Treatment options for HIV/AIDS-related cytomegalovirus retinitis in resource-limited settings
General notes:
People living with HIV (PLHIV) that develop CMV disease have seriously weakened immune systems. Thus,
antiretroviral therapy (ART) is an essential part of the treatment and should be initiated as soon as possible.
Cases of CMV retinitis in PLHIV in resource-limited settings typically involve advanced retinal disease.
The location of CMV retinitis is important. If the retinitis is considered to be “immediately sight-threatening”,
aggressive treatment is required in order to preserve vision.
Prevention is the best treatment! Vision loss from CMV retinitis, plus the related complications of immune recovery
uveitis (IRU) and retinal detachment, can be prevented through early diagnosis followed by prompt treatment.
CMV-specific therapy:
Several issues may impact the approach to treatment in resource-limited settings:
o It may be difficult to determine the severity of CMV retinitis (e.g. whether or not ‘sight-threatening’ disease is
present or absent).
o Treatment options are limited, e.g. alternative systemic antiviral agents such as foscarnet are typically not
available.
o There are limited options for managing any adverse effects of initial therapy (e.g. granulocyte stimulating
factor to treat neutropenia).
Certain health care systems may function more successfully with a consistent treatment protocol. Such protocols will
be setting-specific and depend on the availability of systemic and local therapies, plus access to ophthalmologic
support.
Since CMV retinitis represents a systemic disease, treatment should include systemic anti-CMV therapy, even in
resource-limited settings. Oral valganciclovir (VG) is the preferred choice, given its ease of administration and good
bioavailability.1
o If VG is not available, or oral treatment unable to be tolerated, another option (albeit much more onerous) is
daily intravenous ganciclovir.
Prior to initiating therapy, a complete blood count should be taken, including platelets, plus serum creatinine.
For those with a reduced estimated glomerular filtration rate (eGFR), e.g. between 10-59 ml/min, the dose of VG
should be reduced.
The use of systemic therapy should be avoided (and intravitreal injections given instead) in the following cases:
o Patients with neutrophils ≤500 cells/µl
o Those with a platelet count ≤20,000/ul
o Those with an eGFR of <10 ml/min
Patients without sight-threatening disease
Those without sight-threatening CMV retinitis, i.e. smaller lesions in the periphery of the retina, are best treated
‘systemically’ with valganciclovir (VG) in resource-limited settings, 900 mg twice daily during an induction phase of
14 to 21 days.
o They should then be transitioned to 900 mg once daily in the maintenance phase. Unlike high-income
settings, this transition is typically based upon protocol and not exam findings.
o It is important to monitor for bone marrow suppression in those being prescribed VG.
Patients with sight-threatening disease
Sight-threatening CMV retinitis includes active lesions that are <1500 microns from the fovea or optic nerve.
Patients with sight-threatening disease should be managed aggressively in order to reduce the risk of vision loss.
They should receive systemic therapy with oral valganciclovir (as above) PLUS intravitreal injections of ganciclovir
(2.5 mg in 0.05 mL volume), in addition to ART.
The intravitreal injections result in instant high intraocular drug levels. When used in conjunction with systemic
therapy, intravitreal injections of ganciclovir are typically given weekly and just for 2-3 weeks.
Intravitreal injections alone
Intraocular therapy alone (i.e. intravitreal injections) may be necessary in patients who need to discontinue systemic
therapy with VG because of neutropenia (≤500 cells/µl), thrombocytopenia (≤20,000/µl), or an eGFR<10 mL/min.
Patients initiating therapy with intravitreal injections alone require injections weekly until treatment can be
discontinued (see below).
Although lack of medical personnel trained in this technique may be a barrier to treatment, primary care clinicians can
and have been trained to administer intravitreal injections.2 This is particularly important in areas where VG is not
available (e.g. because of cost).
Limitations of intravitreal injections include:
As of April 2015, VG has been included in the 19th World Health Organization Model list of essential medications.
Tun N, London N, Kyaw MK, et al. CMV retinitis screening and treatment in a resource-poor setting: three-year
experience from a primary care HIV/AIDS programme in Myanmar. J Int AIDS Soc 2011; 14:41.
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They do not reduce the risk of subsequent development of extraocular CMV disease or contralateral retinitis
in patients with unilateral disease.
Intravitreal injections have no effect on CMV-related mortality.
There may be patient acceptance issues for this invasive procedure, but these are generally overcome with
appropriate counseling.
There are a number of possible serious adverse events related to intraocular injections (e.g.
endophthalmitis, vitreous hemorrhage, retinal detachment), but with appropriate training these are highly
infrequent. Minor complications, such as a gritty feeling in the eye for one or two days, or a red eye, are
common but of little clinical consequence.
Intravitreal injections require weekly clinic visits, which could be difficult for certain patients and for their
families.
Duration of anti-CMV therapy
The duration of therapy for CMV retinitis in resource-limited settings is independent of the type of treatment (i.e.
systemic vs. intravitreal alone).
Anti-CMV treatment should be extended until all three of the following conditions are met:
1. Patients have received anti-CMV therapy for a minimum of three months
2. The CMV retinitis is no longer active
3. The patient has received ART for at least three months and has achieved a CD4 count ≥100 cells/µL or a
CD4 count that has increased by >50 cells/µL above baseline
Patients whose CD4 counts remain below 100 cells/µL should be monitored closely for reactivation of CMV retinitis,
and therapy should be restarted if the disease reactivates.
Monitoring
Patients on anti-CMV treatment should be monitored closely in order to:
o evaluate response to therapy
o allow for early detection of immune recovery uveitis (IRU)
o and possible drug-related side effects
If possible, retinal examination (through dilated pupils) should be performed after 2 weeks of induction therapy, and
monthly thereafter while the patient is on anti-CMV treatment.
For patients receiving oral valganciclovir, routine monitoring for drug-related side effects should include a complete
blood count and serum creatinine.
o These should be obtained at a minimum of two weeks after starting therapy and then monthly over the
course of treatment.
Even after successful completion of anti-CMV therapy, patients should continue to be monitored for complications:
o Onset of significant intraocular inflammation secondary to immune recovery uveitis (IRU), a type of immune
reconstitution inflammatory syndrome (IRIS).
o Retinal detachment, which can occur any time, from early in the course of CMV retinitis to many years later.
For this reason, all patients need to be educated about the symptoms of retinal detachment, and advised to
seek medical care promptly following any new visual changes (vision loss, blurring, floaters, etc).
A final word
It is worth repeating that prevention is the best treatment. Vision loss from CMV retinitis, plus the complications of
immune recovery uveitis (IRU) and retinal detachment, can be prevented through early diagnosis followed by prompt
treatment. Since people with active CMV retinitis often have no symptoms initially, early diagnosis can only be
achieved through routine screening of PLHIV having low CD4 counts (i.e. CD4 <100 cells/µl).
Courtesy of
David Heiden, MD
15 May 2015