AIDS-related Cytomegalovirus GI disease

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AIDS-related Cytomegalovirus GI disease

• Leslie K Proctor, M.D.

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GI CMV in AIDS

• An uncommon but serious complication of AIDS
• Advent of HAART has reduced the incidence and
  improved prognosis

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Risk Factors

• CMV Viremia
• Advanced immunosupression
• CD4 count lt 50

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Natural History

• First reported in 1983
• In early case series, patients died within
  several months without CMV-specific treatment
• Complications hemorrhage, perforation
• Even with ganciclovir therapy, without HAART
  median survival for CMV colitis was 4 months, 8
  months for CMV esophagitis
• With HAART, most cases occur in patients not on
  HAART or who have failed HAART

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Natural History

• Yust et al. 2004 European Journal of Clinical
  Microbiology and Infectious Disease
• Large, multi-center prospective cohort study in
  Europe designed to examine the incidence of CMV
  disease and the rate of survival after diagnosis
  in patients with AIDS in pre and post HAART eras
• With CD4 ct lt400, 1.8 of patients on HAART
  developed CMV disease compared to 14 off HAART
• Mortality from CMV decreased from 79 to 42 in
  post-HAART era (represents a 37 decline in
  mortality)

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Clinical Manifestations

• Esophagitis (most common)
• Fever, odynophagia, nausea, occasionally w/
  burning substernal pain
• Causes multiple ulcers at LES, can also cause
  diffuse esophagitis
• Gastritis
• Substernal and/or epigastric burning pain
• Rarely GI hemorrhage
• Enteritis
• 4 of all CMV infections of GI tract
• Generalized abd pain, diarrhea
• Rarely dyspepsia and ileal perforation
• Colitis (2nd most common)
• Fever, weight loss, anorexia, malaise, abdominal
  pain
• Small volume diarrhea, tenesmus, hematochezia
• Mucosal hemorrhage or perforation can occur

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Diagnosis

• Should be suspected when initial eval is
  unrevealing for more common causes of GI disease
  in AIDS
• Remember that multiple pathogens can exist
• Triad
• cardinal symptoms
• visualization of ulcers/erosions
• histological evidence with viral inclusion bodies
• Viral culture of mucosal biopsies for CMV does
  not diagnose CMV disease as patients with AIDS
  can have viremia without detected disease

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Diagnosis

• Laboratory eval
• Test for CMV viremia with PCR, antigen assays, or
  blood culture
• Detection of antibody only helpful if negative

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Diagnosis

• Pathology
• Mucosal inflammation
• Tissue necrosis
• Vascular endothelial involvement
• Cytomegalic cells
• large cells containing eosinphilic intranuclear
  and frequently basophilic intracytoplasmic
  inclusions
• Seen on HE stain

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• Hepatocyte with a large intranuclear inclusion
  body. Surrounded by a clear halo. Dark punctiform
  inclusions are seen also in the cytoplasm. HE
  stain.

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Diagnosis

• Patients with GI CMV infection often have
  concurrent CMV retinitis
• Should have formal ophthalmologic screening for
  retinitis
• Repeat q 6 months until CD4 count is gt 100

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Treatment

• Induction Therapy
• Can use ganciclovir (5 mg/kg IV BID) or foscarnet
  (90 mg/kg IV BID)
• Appears to be equally efficacious, but
  ganciclovir generally preferred 2/2 cost,
  convenience, and safety
• Duration of therapy not well established
• Most require more than 2 weeks
• General guideline is 3-6 weeks depending on
  clinical response of symptoms

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TreatmentMajor Adverse Reactions

• Gancyclovir
• Neutropenia Thrombocytopenia
• Check CBC twice weekly during induction
• If ANC lt 0.5, should administer w/ GCSF
• Dose reduce in renal failure
• Foscarnet
• Elevated Creatinine and electroyte disturbances
  (esp hypocalcemia w/ infusion)
• Monitor lytes twice weekly
• Pre-hydrate with normal saline
• Avoid other nephrotoxic agents

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Treatment Oral Therapy

• Valgancyclovir
• Not studied in GI CMV disease, but proven
  effective in CMV retinitis
• Similar toxicity to IV gancyclovir
• 900 mg daily provides same daily exposure of
  gancyclovir as does IV gancyclovir at 5 mg/kg
• Can use to complete induction, but many still
  recommend only using valgancyclovir after patient
  has responded with IV gancyclovir

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Treatment HAART

• Use of HAART reduces mortality of CMV infection
  more than does CMV specific treatment alone
• Begin after resolution of initial presenting
  symptom
• Caution HAART has been associated with
  complications of CMV retinitis related to immune
  recovery

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Maintenance Therapy

• No universal agreement
• Little post- HAART data (pre-HAART data showed no
  benefit)
• Currently not recommended by the IDSA routinely
• Patients may benefit from 900 mg oral
  valgancyclovir daily if they have had a relapse
  of disease
• Must undergo reinduction
• If therapy is discontinued, regular monitoring
  should continue (i.e. yearly eye exams for CMV
  retinitis)

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Salvage Therapy

• Used if a patient fails to respond to initial
  therapy
• Switch to alternate agent (i.e. if used
  gancyclovir use foscarnet and vice versa)
• Can use foscarnet gancyclovir
• Cidofovir
• Can cause severe, irreversible nephrotoxicity
• Can give saline hydration and probenecid
  concomitantly to reduce risk
• Should measure urine protein and creatinine prior
  to each dose (discontinue if 2 protein or
  creatinine increases by gt 0.5)
• Other adverse effects neutropenia, peripheral
  neuropathy, low intraocular pressure, anterior
  uveitis, alopecia

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References

• Gallant, J, Moore, R, Richman, D, et al.
  Incidence and natural history of cytomegalovirus
  disease in patients with advanced human
  immunodeficiency virus disease treated with
  zidovudine. J Infect Dis 1992 1661223.
• Jacobson, Mark A. AIDS-related cytomegalovirus
  gastrointestinal disease. UpToDate Feb 1 2007
  update.
• Whitley, RJ, Jacobson, MA, Friedberg, DN, et al.
  Guidelines for the treatment of cytomegalovirus
  diseases in patients with AIDS in the era of
  potent antiretroviral therapy Recommendations of
  an international panel. Arch Intern Med 1998
  158957.
• Yust, I, Fox, Z, Burke, M, et al. Retinal and
  extraocular cytomegalovirus and end-organ disease
  in HIV-infected patients in Europe a EuroSIDA
  study, 1994-2001. Eur J Clin Microbiol Infect Dis
  2004 23550