Downloaded from http://journals.lww.com/jaids by BhDMf5ePHKbH4TTImqenVAHxkFJp/XpPk1L/H3vMGwqMxG9jwOd8eJPG+b4DlKuAX44qu/vwzmc= on 07/29/2018 CLINICAL SCIENCE Cytomegalovirus Viremia, Mortality, and End-Organ Disease Among Patients With AIDS Receiving Potent Antiretroviral Therapies David A. Wohl, MD,* Donglin Zeng, PhD,† Paul Stewart, PhD,† Nicolas Glomb, BA,* Timothy Alcorn, PhD,‡ Suzanne Jones, PhD,§ Jean Handy, PhD,§ Susan Fiscus, PhD,§ Adriana Weinberg, MD, k Deepthiman Gowda, MD,¶ and Charles van der Horst, MD* Objective: To determine the association of cytomegalovirus (CMV) viremia with CMV disease and death in patients with AIDS. Design and setting: Prospective, observational cohort study conducted at a university hospital. Methods: A cohort of 190 subjects with AIDS who were CMV seropositive and had no history or evidence of CMV disease were longitudinally evaluated for signs and symptoms of CMV disease and CMV viremia with plasma CMV DNA polymerase chain reaction (PCR) and whole blood CMV hybrid capture. Results: A total of 187 subjects had at least 1 study visit following entry. At baseline, the median CD4 + cell count and plasma HIV RNA level were 110/mL (range = 3–620/mL) and 47,973 copies/mL (,30– .750,000 copies/mL), respectively. Highly active antiretroviral therapy (HAART) use increased from 87.5% during the 1st study year to 98.5% by the end of the study. During a median follow-up of 334 days, 16% (30) of the subjects died and 2 (6%) developed CMV disease. No deaths were attributable to CMV disease; 4 subjects who died developed CMV prior to death. Baseline HIV viral load and final CD4 + cell count were significantly and independently associated with mortality. Detectable plasma CMV DNA PCR was an independent predictor of death even after adjusting for HIV RNA level and CD4 + cell count prior to death (P = 0.038). In contrast, whole blood CMV hybrid capture did not predict mortality. The CMV assays neither collectively nor individually were found to be associated with the few cases of CMV disease. Conclusions: In patients with AIDS and seropositive for CMV, detection of CMV viremia with plasma CMV DNA PCR was predictive of death and provided additional prognostic information on the risk of all cause-mortality beyond that obtained with CD4 + cell count and HIV viral load testing alone. Detection of CMV viremia by plasma with CMV DNA PCR in patients with AIDS, particularly those with low CD4 + cell counts, provides additional rationale for optimization of antiretroviral therapy and consideration for pre- emptive anti-CMV therapy. Key Words: cytomegalovirus, AIDS, viremia, antiretroviral therapy (J Acquir Immune Defic Syndr 2005;38:538–544) P otent combination antiretroviral therapies have led to sub- stantial declines in the incidence of opportunistic diseases, including those caused by cytomegalovirus (CMV). 1–4 While the incidence of CMV end-organ diseases among persons with AIDS has declined to approximately 25% of that seen prior to the advent of highly active antiretroviral therapy (HAART), CMV continues to occur particularly among HIV-infected patients who because of drug failure, treatment nonadherence, or therapy intolerance are not receiving maximal benefit from HAART. 5–7 As the diagnosis of CMV end-organ disease is made only after viral-mediated tissue destruction becomes clinically evident, assays to detect CMV viremia have been investigated as potential predictors of CMV-related disease in persons with advanced HIV infection. In studies conducted prior to the availability of HAART, CMV DNA detected in the blood by polymerase chain reaction (PCR) was associated with in- creased risk of both development of CMV end-organ disease and death. 8–10 Further, the risks of CMV disease and mortality were found by Spector et al 8 to be directly proportional to plasma CMV DNA levels as measured by an in-house assay. This assay has subsequently been found to correlate with the more widely available plasma Amplicor (Basel, Switzerland) COBAS CMV DNA PCR assay. 11 There are fewer data Received for publication August 19, 2004; accepted December 23, 2004. From the *Division of Infectious Diseases and †Department of Biostatistics, The University of North Carolina, Chapel Hill, NC; ‡Esoterix Inc., Brentwood, TN; §Department of Microbiology, The University of North Carolina, Chapel Hill, NC; k Division of Pediatrics, The University of Colorado Health Sciences Center, Denver, CO; and {Department of Medicine, New York Presbyterian Hospital, New York, NY. Supported by a National Center for Research Resources–NIH CAP Award (MO1 RR00046-41S1) and an unrestricted grant from Roche Pharma- ceuticals, Inc. Support also provided by the UNC General Clinical Research Center (GCRC), a National Center for Research Resources funded program (RR00046), and the UNC AIDS Clinical Trials Unit (5 U01 AI25868-17). Preparation of this report was facilitated by the Biostatistics Core of the UNC Center for AIDS Research (CFAR), which is an NIH-funded program (AI 50410-04). The CMV viremia assays were performed at no charge by the Laboratory Corp. of America, Research Triangle Park, NC. Reprints: David A. Wohl, Division of Infectious Diseases, The University of North Carolina, Chapel Hill, Campus Box #7215, Chapel Hill, NC 27599 (e-mail: wohl@med.unc.edu). Copyright Ó 2005 by Lippincott Williams & Wilkins 538 J Acquir Immune Defic Syndr  Volume 38, Number 5, April 15 2005