AIDS-related cytomegalovirus gastrointestinal disease
- Mark A Jacobson, MD
Mark A Jacobson, MD
- Clinical Health Sciences Professor of Medicine
- University of California San Francisco
Cytomegalovirus (CMV) gastrointestinal disease is an uncommon but serious complication of AIDS. Prior to the availability of potent antiretroviral therapy (ART), CMV gastrointestinal disease occurred in up to 5 percent of patients with AIDS, primarily in those with advanced immunosuppression. However, the incidence of CMV gastrointestinal disease has decreased substantially since ART became available [1,2]. (See "Selecting antiretroviral regimens for the treatment-naïve HIV-infected patient".)
A discussion of the pathogenesis and clinical manifestations of other CMV-related diseases in HIV-infected patients is found elsewhere. (See "AIDS-related cytomegalovirus neurologic disease" and "Pathogenesis, clinical manifestations, and diagnosis of AIDS-related cytomegalovirus retinitis" and "Cytomegalovirus infection as a cause of pulmonary disease in HIV-infected patients".)
In persons with prior CMV infection and a CD4 cell count <50 cells/microL, reactivation of latent virus causes a systemic disease that is characterized by intermittent or constant viremia which can lead to colonization or localized infections in one or multiple target organs, including the gastrointestinal tract . CMV gastrointestinal disease was first reported as a manifestation of AIDS in 1983. In early case series, patients generally died within several months without CMV-specific treatment, and hemorrhage or perforation often complicated the course of disease. The prognosis of such patients remained poor despite the advent of antiviral drugs for the treatment of CMV. As an example, the median survival was reported to be four months after the diagnosis of CMV colitis and eight months after CMV esophagitis, even with ganciclovir therapy [4-6]. However, as with all HIV-related opportunistic infections, the prognosis has improved markedly with the utilization of antiretroviral therapy (ART). (See 'Impact of ART' below.)
Risk factors — Most cases of CMV disease occur in the setting of advanced immunosuppression, with CD4 cell counts < 50 cells/microL . The presence of CMV in blood (as measured by culture, CMV DNA amplification, or antigen detection) is also a risk factor for the development of invasive disease . However, patients with viremia may not have invasive disease. (See 'Viral detection' below.)
Impact of ART — The prognosis of patients with AIDS and CMV gastrointestinal disease has improved dramatically since effective ART became available in the late 1990s [9,10]. Most cases of end organ disease now occur in patients who are not receiving ART, either due to late diagnosis of HIV disease or poor adherence to prescribed therapy.
- Baril, L, Jouan, M, Caumes, E, et al. The impact of highly active antiretroviral therapy on the incidence of CMV disease in AIDS patients (abstract #I-31). 37th Interscience Conference on Antimicrobial Agents and Chemotherapy, 1997; Toronto, Canada.
- Hammer SM, Squires KE, Hughes MD, et al. A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. AIDS Clinical Trials Group 320 Study Team. N Engl J Med 1997; 337:725.
- Gallant JE, Moore RD, Richman DD, et al. Incidence and natural history of cytomegalovirus disease in patients with advanced human immunodeficiency virus disease treated with zidovudine. The Zidovudine Epidemiology Study Group. J Infect Dis 1992; 166:1223.
- Chachoua A, Dieterich D, Krasinski K, et al. 9-(1,3-Dihydroxy-2-propoxymethyl)guanine (ganciclovir) in the treatment of cytomegalovirus gastrointestinal disease with the acquired immunodeficiency syndrome. Ann Intern Med 1987; 107:133.
- Mentec H, Leport C, Leport J, et al. Cytomegalovirus colitis in HIV-1-infected patients: a prospective research in 55 patients. AIDS 1994; 8:461.
- Wilcox CM, Straub RF, Schwartz DA. Cytomegalovirus esophagitis in AIDS: a prospective evaluation of clinical response to ganciclovir therapy, relapse rate, and long-term outcome. Am J Med 1995; 98:169.
- 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. International AIDS Society-USA. Arch Intern Med 1998; 158:957.
- Shinkai M, Bozzette SA, Powderly W, et al. Utility of urine and leukocyte cultures and plasma DNA polymerase chain reaction for identification of AIDS patients at risk for developing human cytomegalovirus disease. J Infect Dis 1997; 175:302.
- Yust I, Fox Z, Burke M, et al. Retinal and extraocular cytomegalovirus end-organ disease in HIV-infected patients in Europe: a EuroSIDA study, 1994-2001. Eur J Clin Microbiol Infect Dis 2004; 23:550.
- Salzberger B, Hartmann P, Hanses F, et al. Incidence and prognosis of CMV disease in HIV-infected patients before and after introduction of combination antiretroviral therapy. Infection 2005; 33:345.
- Wilcox CM, Straub RF, Schwartz DA. Prospective endoscopic characterization of cytomegalovirus esophagitis in AIDS. Gastrointest Endosc 1994; 40:481.
- Vanegas F, Montalvo RD, Alvarez OA, et al. Massive upper gastrointestinal hemorrhage due to cytomegalovirus infection in two patients with acquired immunodeficiency syndrome. South Med J 2000; 93:235.
- Chamberlain RS, Atkins S, Saini N, White JC. Ileal perforation caused by cytomegalovirus infection in a critically ill adult. J Clin Gastroenterol 2000; 30:432.
- Wilcox CM, Schwartz DA. Symptomatic CMV duodenitis. An important clinical problem in AIDS. J Clin Gastroenterol 1992; 14:293.
- Kyriazis AP, Mitra SK. Multiple cytomegalovirus-related intestinal perforations in patients with acquired immunodeficiency syndrome. Report of two cases and review of the literature. Arch Pathol Lab Med 1992; 116:495.
- Dieterich DT, Rahmin M. Cytomegalovirus colitis in AIDS: presentation in 44 patients and a review of the literature. J Acquir Immune Defic Syndr 1991; 4 Suppl 1:S29.
- Orenstein JM, Dieterich DT. The histopathology of 103 consecutive colonoscopy biopsies from 82 symptomatic patients with acquired immunodeficiency syndrome: original and look-back diagnoses. Arch Pathol Lab Med 2001; 125:1042.
- Epstein JB, Sherlock CH, Wolber RA. Oral manifestations of cytomegalovirus infection. Oral Surg Oral Med Oral Pathol 1993; 75:443.
- Panel on Opportunistic Infections in HIV-Infected Adults and Adolescents. Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America http://aidsinfo.nih.gov/contentfiles/lvguidelines/adult_oi.pdf (Accessed on November 18, 2013).
- Rene E, Marche C, Chevalier T, et al. Cytomegalovirus colitis in patients with acquired immunodeficiency syndrome. Dig Dis Sci 1988; 33:741.
- Goodgame RW, Genta RM, Estrada R, et al. Frequency of positive tests for cytomegalovirus in AIDS patients: endoscopic lesions compared with normal mucosa. Am J Gastroenterol 1993; 88:338.
- Goodgame RW. Gastrointestinal cytomegalovirus disease. Ann Intern Med 1993; 119:924.
- Frank D, Raicht RF. Intestinal perforation associated with cytomegalovirus infection in patients with acquired immune deficiency syndrome. Am J Gastroenterol 1984; 79:201.
- Spector SA, Wong R, Hsia K, et al. Plasma cytomegalovirus (CMV) DNA load predicts CMV disease and survival in AIDS patients. J Clin Invest 1998; 101:497.
- Laine L, Bonacini M, Sattler F, et al. Cytomegalovirus and Candida esophagitis in patients with AIDS. J Acquir Immune Defic Syndr 1992; 5:605.
- Dieterich DT, Poles MA, Lew EA, et al. Treatment of gastrointestinal cytomegalovirus infection with twice-daily foscarnet: a pilot study of safety, efficacy, and pharmacokinetics in patients with AIDS. Antimicrob Agents Chemother 1997; 41:1226.
- Nelson MR, Connolly GM, Hawkins DA, Gazzard BG. Foscarnet in the treatment of cytomegalovirus infection of the esophagus and colon in patients with the acquired immune deficiency syndrome. Am J Gastroenterol 1991; 86:876.
- Dieterich DT, Kotler DP, Busch DF, et al. Ganciclovir treatment of cytomegalovirus colitis in AIDS: a randomized, double-blind, placebo-controlled multicenter study. J Infect Dis 1993; 167:278.
- Blanshard C, Benhamou Y, Dohin E, et al. Treatment of AIDS-associated gastrointestinal cytomegalovirus infection with foscarnet and ganciclovir: a randomized comparison. J Infect Dis 1995; 172:622.
- Martin DF, Sierra-Madero J, Walmsley S, et al. A controlled trial of valganciclovir as induction therapy for cytomegalovirus retinitis. N Engl J Med 2002; 346:1119.
- Blanshard C. Treatment of HIV-related cytomegalovirus disease of the gastrointestinal tract with foscarnet. J Acquir Immune Defic Syndr 1992; 5 Suppl 1:S25.
- Macdonald JC, Torriani FJ, Morse LS, et al. Lack of reactivation of cytomegalovirus (CMV) retinitis after stopping CMV maintenance therapy in AIDS patients with sustained elevations in CD4 T cells in response to highly active antiretroviral therapy. J Infect Dis 1998; 177:1182.
- Tural C, Romeu J, Sirera G, et al. Long-lasting remission of cytomegalovirus retinitis without maintenance therapy in human immunodeficiency virus-infected patients. J Infect Dis 1998; 177:1080.
- NATURAL HISTORY
- Risk factors
- Impact of ART
- CLINICAL MANIFESTATIONS
- DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS
- When to suspect CMV gastrointestinal disease
- Endoscopic evaluation
- Additional testing
- - Viral detection
- - Serology
- Ophthalmologic evaluation in all patients with CMV disease
- Differential diagnosis
- Induction therapy
- - The use of oral therapy
- - Duration
- - When to initiate ART
- Maintenance therapy
- Treatment failure
- PATIENT MONITORING
- SOCIETY GUIDELINE LINKS
- SUMMARY AND RECOMMENDATIONS