|Valganciclovir||Preferred for most cases of CMV-R; efficacy comparable to IV forms of therapy with fewer side effects. Particularly effective when combined with ART. Should also be used as 2o prophylaxis when GCV implant used to reduce risk of visceral CMV disease and decrease mortality.|
|Ganciclovir||Difficult to obtain in oral formulation with no benefit over valganciclovir. IV GCV can be substituted for valganciclovir in patients unable to tolerate oral anti-CMV therapy. GCV implant often the preferred therapy in pts with CMV-R threatening optic nerve or fovea, particularly in pts not taking or poorly responsive to HAART.|
|Foscarnet||IV FOS not used as primary therapy for CMV-R but may be useful in patients with GCV resistance or severe bone marrow suppression. Short half-life, nephrotoxicity, and limitation to IV form are major drawbacks. Intravitreal FOX can be useful as short-term therapy for lesions threatening optic nerve and macula.|
|Cidofovir||IV CDV has efficacy comparable to GCV implant plus oral therapy but usually less well tolerated because of nephrotoxicity, long duration of infusion, and side effects of probenecid that must be given with cidofovir to reduce risk of renal disease. May be useful in pts with GCV resistance. Intravitreous CDV should not be used.|
|Pathogen||1st Line Agent||2nd Line Agent|
Comment: This article reviews the evolution of CMV-R from a pre-terminal manifestation of AIDS to a chronic, manageable disease with numerous complications. Points of emphasis include retinal detachment, immune recovery uveitis, and visual disturbances (reduced contrast sensitivity, altered color vision, visual field abnormalities) that can occur in HIV+ pts even without infectious retinopathy.
Comment: This review of immune recovery uveitis (IRU) summarizes risk factors (in addition to improved immunity itself, a low CD4 count at time of initiation of ART, and involvement of a larger proportion of retina), effect on vision and morbidity, and current treatment. A precise definition of IRU remains lacking.
Comment: In a small, non-randomized, prospective, consecutive, interventional case series, intravitreal triamcinolone acetonide appeared to be more effective for treatment of macular edema caused by immune recovery uveitis than historical controls have shown with periocular corticosteroid injections.
Comment: In 10-yr prospective observational study from 1993-2003, 2-yr incidence of resistance was 28% among pts enrolled before 1996 and 9% among those enrolled in or after 1996 (P=.001). All cases of resistance occurred among pts with CD4 <50, and + CMV Cx results at baseline associated with approximately 4-fold increase in resistance. Better control of CMV replication may have contributed to this decrease.
Comment: In a large cohort study of patients with AIDS in the HAART era, there has been substantial decline in incidence of CMV retinitis from compared to pre-HAART era. Incidence of CMV retinitis estimated from retrospective data was 5.60/100 person-yrs. Of 360 patients with CMV-R, over 75% had pre-existing CMV-R. Nevertheless, new cases continue to occur, and there is population of patients with long-standing retinitis who will require management.
Comment: In the HAART era, CMV-R and other ocular opportunistic infections are associated with intraocular inflammation, structural ocular complications, and visual impairment. Patients with newly diagnosed CMV-R have eye examination findings similar to those seen in pre-HAART era.
Comment: In HAART era, zone 1 involvement and retinal detachment remain most common causes of visual acuity loss among patients with CMV-R. Immune recovery uveitis due to ART associated with vision loss from cataract and CME also are common causes of loss of visual acuity.
Comment: CMV-R in pts without HIV has clinical course similar to that in pts with AIDS treated with HAART, except incidence of retinal detachment lower for pts without AIDS. Cessation of anti-CMV therapy often possible in pts who discontinue or reduce their immunomodulatory therapy.
Comment: Summary of trends in incidence of CMV-R and treatment recommendations for affected patients in era of HAART. Systemic therapy, with or without GCV implant, recommended for all pts with newly Dx'd CMV-R to increase survival and possibly decrease risk of immune recovery uveitis.
Comment: Patients with CMV-R randomized to treatment with GCV implant had low risk of serious complications in first 60 days after surgery. Vitreous hemorrhage was most commonly observed complication and resolved in all cases.
Comment: Compared with rates reported in pre-HAART era of 2nd eye involvement (approximately 0.40/person-year) and retinal detachment (approximately 0.50/PY), rates of these events reduced among pts in the HAART era. However, among patients with CD4 <50, rates more similar to those from pre-HAART era.
Comment: Although retinitis progression in pts with CMV-R treated with anti-CMV therapy and HAART much less than in pre-HAART era, significant risk factors for retinitis progression included low CD4 count, positive CMV viral load, longer time from AIDS Dx and low Karnofsky score
Comment: Study of nearly 600 patients with CMV-R: use of HAART associated with 96% reduction in mortality in pts who developed immune recovery compared to 49% reduction in those who did not. In pts with profound immunodeficiency despite HAART, continued use of HAART and systemic anti-CMV therapy predicted to reduce risk of mortality by 65%, over and above benefits of PCP and MAC prophylaxis.
Comment: In HAART era, CMV-R associated with reduced vision-related quality of life in pts both with newly Dx'd and long-standing disease.
Comment: In HAART era, pts still present with CMV disease, and resistance or intolerance to HAART does develop, which may give rise to resurgence of CMV syndromes in AIDS pts. Treatment should be based on both systemic health and local ocular factors.
Comment: In 3 clinical trials of CMV-R conducted between 1990-96 (pre-HAART era), visual loss common, with major causes of visual loss in pts being retinal detachment and either optic nerve or macular involvement. However, visual outcomes better after 1992, even before availability of HAART.
Comment: Detection of CMV resistant to GCV (IC50 > 6.0 micromol/l) in either the blood or urine of a pt with CMV-R associated with an increased risk of adverse ocular outcomes, including a roughly 5-fold increased risk in odds of progression.
Comment: High incidence of cataract following repair of CMV-R-related retinal detachment surgery with silicone oil tamponade. Posterior capsule opacification occurs rapidly after cataract surgery in these patients.
Comment: In eyes with CMV-R, prevalence of a visual acuity measurement of 20/50 or worse or 20/200 or worse at time of CMV-R Dx was 33% and 17%, respectively. Incidence of vision loss did not differ based on type of anti-CMV therapy used, but pts receiving HAART had approximately 75% lower risk of visual impairment.
Comment: Multicenter study of pts with newly Dx'd (incident) or previously Dx'd (prevalent) CMV-R: nearly 2/3 of pts with prevalent disease had successfully discontinued anti-CMV therapy, immune recovery uveitis had been Dx'd in 16%, and incident cases more likely than prevalent cases to be female, African-American, and uninsured.
Comment: In study of 87 pts with CMV-R who had paired blood and vitreous specimens, 13 (15%) had either a GCV resistance-conferring mutation or a polymorphism in CMV UL97 gene. 11 of the 13 mutations or polymorphisms in vitreous also identified in blood
Comment: In this randomized clinical trial, PO valganciclovir as effective as IV GCV for induction treatment of CMV-R and was convenient and effective for long-term management of CMV-R in pts with AIDS. However, progression of retinitis occurred in 10% in both groups despite continued therapy.
Comment: Single case report describing successful control of CMV-R over 1 year with intravitreous injections up to twice weekly of high-dose GCV 3 mg/ml and FOS2.4 mg/ml.
Comment: Use of HAART associated with 60% reduction in retinal detachment rate (P<.001), with greatest reduction in HAART responders. No significant difference in risk of retinal detachment in eyes treated with GCV implants vs. systemic anti-CMV therapy only.
Comment: In pre-HAART study of CMV-R, risk factors at baseline for progression of retinitis while receiving treatment included smaller area involved, active margins, and posterior location. Risk factors for development of retinitis in uninvolved fellow eyes included blood and urine Cx positive for CMV and lower CD8 count.
Comment: In this study of 33 pts with CMV-R and good response to HAART, incidence rate of immune recovery uveitis (IRU) was 0.109/person-year, lower than reported in some other studies, but decreased vision occurred in some pts due to macular edema, epiretinal membrane, or optic disc neovascularization.
Comment: Summary of treatment options for CMV-R in HAART era. Previous short-term therapies are being adapted to long-term management of what has in many cases become a chronic disease.
Comment: In this randomized clinical trial in pts with AIDS and CMV-R, combination of oral GCV and GCV implant reduced incidence of new CMV disease and delayed progression of retinitis compared to implant + oral placebo. Treatment with oral or IV GCV also reduced the risk of KS.
Comment: In this study of 15 pts with CMV-R and immune recovery from HAART (med. CD4 count 297), none had recurrence of retinitis after discontinuation of anti-CMV therapy for 3-16 mos (median 8 mos).
Comment: In pts undergoing routine GCV implant exchange, initial exchange procedure well tolerated with continued long-term control of CMV-R. Multiple re-entries through same wound may be associated with increased risk for vitreous hemorrhage.
Comment: In this randomized clinical trial of CMV-R in pre-HAART era, IVGCV and FOS were comparably effective for treatment of CMV-R, but retinitis recurred in almost all pts over time in both groups. Mortality significantly lower in FOS-treated group, possibly due to its weak antiretroviral effect.
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