Preventing Cytomegalovirus (CMV) Organ Damage With Valganciclovir in People With HIV

A Phase III, Prospective, Randomized, Double-Blind Trial of Valganciclovir Pre-Emptive Therapy for Cytomegalovirus (CMV) Viremia as Detected by Plasma CMV DNA PCR Assay

Cytomegalovirus (CMV) infection is a common opportunistic infection (OI) in HIV patients. The purpose of this study is to find out whether valganciclovir, an antiviral approved by the FDA for the treatment of CMV in the eye, is safe and effective in preventing CMV organ damage in people with HIV.

Study Overview

• Status: Completed
• Conditions: HIV Infections; Cytomegalovirus Infections
• Intervention / Treatment: Drug: Valganciclovir

Detailed Description

CMV infection, most commonly of the retina (also known as CMV retinitis), is a common OI observed in HIV patients. Despite treatment, CMV retinitis can result in severe visual impairment and CMV disease is associated with reduced survival time. HIV patients receiving highly active antiretroviral therapy (HAART) for HIV infection who have CD4 counts less than 100 cells/mm3 may be at increased risk of CMV infection and its complications. Valganciclovir was approved by the FDA on March 29, 2001 for treatment of the symptoms of CMV retinitis in patients with weakened immune systems, including people with HIV and AIDS. This study will evaluate the safety and efficacy of valganciclovir in preventing CMV organ damage in HIV patients.

This study will last approximately 6 years. Step 1 is the longitudinal screening phase of the study. Patients at high risk for CMV disease who are enrolled in the study will be screened every 8 weeks for CMV in the blood; medical history assessment, physical examination, and blood work will occur at each visit. Additional blood collection to monitor HIV infection will occur every 16 weeks. Patients will undergo opthalmologic examination every 24 weeks. Patients who develop detectable CMV in their blood during Step 1 then enter Step 2 of the study.

In version 3.0 of this study, participants who test positive for CMV viremia or who are currently in Step 2 will be automatically enrolled into Step 4 and will be randomly assigned to one of two groups: 1) 900 mg valganciclovir twice daily for 3 weeks, followed by 900 mg valganciclovir daily, or 2) placebo. Participants will enter Step 3 if and when they develop CMV end-organ disease, at which point all participants will be offered 900 mg valganciclovir twice daily for 3 weeks, then 900 valganciclovir daily thereafter.

• Study Type: Interventional
• Enrollment: 350
• Phase: Phase 3

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00935
    • Puerto Rico-AIDS CRS
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Alabama Therapeutics CRS
  • California
    • Los Angeles, California, United States, 90095
      • UCLA CARE Center CRS
    • Los Angeles, California, United States, 90033
      • USC CRS
    • Palo Alto, California, United States, 94305
      • Stanford CRS
    • San Diego, California, United States, 92103
      • Ucsd, Avrc Crs
    • San Francisco, California, United States, 94110
      • Ucsf Aids Crs
    • San Jose, California, United States, 95128
      • Santa Clara Valley Med. Ctr.
    • San Mateo, California, United States, 94305
      • San Mateo County AIDS Program
    • San Rafael, California, United States, 94903
      • Marin County Dept. of Health & Human Services, HIV/AIDS Program & Specialty Clinic
  • Colorado
    • Aurora, Colorado, United States, 80262
      • University of Colorado Hospital CRS
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University CRS (GU CRS)
  • Florida
    • Miami, Florida, United States, 33136
      • Univ. of Miami AIDS CRS
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • The Ponce de Leon Ctr. CRS
  • Hawaii
    • Honolulu, Hawaii, United States, 96816
      • Univ. of Hawaii at Manoa, Leahi Hosp.
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Cook County Hosp. CORE Ctr.
    • Chicago, Illinois, United States, 60611
      • Northwestern University CRS
    • Chicago, Illinois, United States, 60612
      • Rush Univ. Med. Ctr. ACTG CRS
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana Univ. School of Medicine, Infectious Disease Research Clinic
    • Indianapolis, Indiana, United States, 46202
      • Methodist Hosp. of Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana Univ. School of Medicine, Wishard Memorial
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Univ. of Iowa Healthcare, Div. of Infectious Diseases
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins Adult AIDS CRS
    • Baltimore, Maryland, United States, 21201
      • IHV Baltimore Treatment CRS
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • BMC, Div. of Ped Infectious Diseases
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital ACTG CRS
    • Boston, Massachusetts, United States, 02118
      • Bmc Actg Crs
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Med. Ctr., ACTG CRS
    • Boston, Massachusetts, United States, 02215
      • Brigham and Women's Hosp. ACTG CRS
    • Fall River, Massachusetts, United States, 02720
      • SSTAR, Family Healthcare Ctr.
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota, ACTU
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington U CRS
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Univ. of Nebraska Med. Ctr., Durham Outpatient Ctr.
  • New York
    • Buffalo, New York, United States, 14215
      • SUNY - Buffalo, Erie County Medical Ctr.
    • New York, New York, United States, 10003
      • Beth Israel Med. Ctr., ACTU
    • New York, New York, United States, 10016
      • NY Univ. HIV/AIDS CRS
    • New York, New York, United States, 10011
      • Cornell CRS
    • New York, New York, United States, 10021
      • Weill Med. College of Cornell Univ., The Cornell CTU
    • New York, New York, United States, 10032
      • Columbia Univ., HIV Prevention and Treatment Medical Ctr.
    • Rochester, New York, United States, 14642
      • Univ. of Rochester ACTG CRS
    • Rochester, New York, United States, 14607
      • AIDS Care CRS
    • Rochester, New York, United States, 14642
      • McCree McCuller Wellness Ctr. at the Connection, Infectious Disease Unit
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • Unc Aids Crs
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • Univ. of Cincinnati CRS
    • Cleveland, Ohio, United States, 44106
      • Case CRS
    • Cleveland, Ohio, United States, 44109
      • MetroHealth CRS
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation, Div. of Medicine, Infectious Diseases
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Hosp. of the Univ. of Pennsylvania CRS
    • Philadelphia, Pennsylvania, United States, 19104
      • Univ. of Pennsylvania Health System, Presbyterian Med. Ctr.
    • Pittsburgh, Pennsylvania, United States, 15213
      • Pitt CRS
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • The Miriam Hosp. ACTG CRS
    • Providence, Rhode Island, United States, 02906
      • Rhode Island Hosp.
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Vanderbilt Therapeutics CRS
  • Texas
    • Dallas, Texas, United States, 75235
      • Univ. of Texas Southwestern Med. Ctr., Amelia Court Continuity Clinic
    • Galveston, Texas, United States, 77555
      • Univ. of Texas Medical Branch, ACTU
  • Washington
    • Seattle, Washington, United States, 98104
      • University of Washington AIDS CRS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years and older (ADULT, OLDER_ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Note: Per a recommendation from NIAID Therapeutic Trials Data Safety Monitoring Board (DSMB), this trial will close on 10/03/05. The DSMB has determined that the study will reach the primary objective. All participants not on valganciclovir must complete all study evaluations by 08/31/05; all participants taking valganciclovir must complete study evaluations by 10/03/05.

Inclusion Criteria for Step 1:

• HIV infected
• Viral load greater than 400 copies/ml
• CD4 count less than 100 cells/mm3
• Have taken HAART for 3 months or longer OR are not taking HAART and do not plan to start HAART for at least 3 months after study entry
• Have serum CMV IgG antibodies
• Have consent of parent or guardian if under 18 years of age
• Willing to use acceptable forms of contraception

Exclusion Criteria for Step 1:

• History of CMV end-organ disease
• Certain antiviral drugs for CMV prophylaxis within 8 weeks of study entry
• Pregnant or breastfeeding
• Currently require ongoing foscarnet or cidofovir. Limited courses of foscarnet or cidofovir for the treatment of diseases other than CMV are permitted if approved by the protocol chairs.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Masking: DOUBLE

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Study Chair: Mark Jacobson, MD, University of California, San Francisco and San Francisco General Hospital; Study Chair: David A. Wohl, MD, University of North Carolina, Chapel Hill

Publications and helpful links

General Publications

• Cocohoba JM, McNicholl IR. Valganciclovir: an advance in cytomegalovirus therapeutics. Ann Pharmacother. 2002 Jun;36(6):1075-9. doi: 10.1345/aph.1A393.
• De Clercq E. Antiviral drugs in current clinical use. J Clin Virol. 2004 Jun;30(2):115-33. doi: 10.1016/j.jcv.2004.02.009.
• Erice A, Tierney C, Hirsch M, Caliendo AM, Weinberg A, Kendall MA, Polsky B; AIDS Clinical Trials Group Protocol 360 Study Team. Cytomegalovirus (CMV) and human immunodeficiency virus (HIV) burden, CMV end-organ disease, and survival in subjects with advanced HIV infection (AIDS Clinical Trials Group Protocol 360). Clin Infect Dis. 2003 Aug 15;37(4):567-78. doi: 10.1086/375843. Epub 2003 Jul 29.
• Reusser P. Oral valganciclovir: a new option for treatment of cytomegalovirus infection and disease in immunocompromised hosts. Expert Opin Investig Drugs. 2001 Sep;10(9):1745-53. doi: 10.1517/13543784.10.9.1745.
• Wohl DA, Kendall MA, Andersen J, Crumpacker C, Spector SA, Feinberg J, Alston-Smith B, Owens S, Chafey S, Marco M, Maxwell S, Lurain N, Jabs D, Benson C, Keiser P, Jacobson MA; A5030 Study Team. Low rate of CMV end-organ disease in HIV-infected patients despite low CD4+ cell counts and CMV viremia: results of ACTG protocol A5030. HIV Clin Trials. 2009 May-Jun;10(3):143-52. doi: 10.1310/hct1003-143.

Study record dates

Study Major Dates

• Study Start: August 1, 2000
• Study Completion (ACTUAL): February 1, 2006

Study Registration Dates

• First Submitted: August 7, 2000
• First Submitted That Met QC Criteria: August 30, 2001
• First Posted (ESTIMATE): August 31, 2001

Study Record Updates

• Last Update Posted (ACTUAL): November 1, 2021
• Last Update Submitted That Met QC Criteria: October 28, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: Antiviral Agents; Cytomegalovirus; Cytomegalovirus Infections; Polymerase Chain Reaction; Administration, Oral; Viremia; Ganciclovir; DNA, Viral
• Additional Relevant MeSH Terms: Pathologic Processes; Virus Diseases; Disease Attributes; DNA Virus Infections; Herpesviridae Infections; Infections; Communicable Diseases; Cytomegalovirus Infections; Anti-Infective Agents; Antiviral Agents; Valganciclovir
• Other Study ID Numbers: A5030; 10170 (Other Identifier: CTEP); ACTG A5030; AACTG A5030