A Study of Anal Cancer Development in HIV Infected People

Anal Dysplasia: A Substudy of a Large, Simple Trial Comparing Two Strategies for Management of Anti-Retroviral Therapy (The SMART Study)

The purpose of this study is to compare the development of abnormal cell growth or cancer in the anal region of individuals who are receiving one of two different anti-HIV treatment strategies.

Study Overview

• Status: Completed
• Conditions: HIV Infections; Anus Neoplasms

Detailed Description

Human papillomavirus (HPV) is a common viral infection among men and women. Individuals with HPV are at risk for anal dysplasia, a condition that may lead to anal cancer. It has been observed that HIV progresses more rapidly in individuals coinfected with HPV and HIV, compared to people with either disease alone. Studies that have investigated the effect of highly active antiretroviral therapy (HAART) on the progression of anal dysplasia have been contradictory and inconclusive. The role of CD4 count and HIV suppression and their contributions to the progression of anal disease needs to be determined. This trial is a substudy of a study of management of antiretroviral therapy (SMART). In the SMART study, patients will participate in one of two strategies: a drug conservation (DC) strategy and a viral suppression (VS) strategy. Participants in the DC group will stop or defer HAART, then receive episodic HAART treatment for the minimum time needed to maintain a CD4 cell count of at least 250 cells/mm3. Participants in the VS group will receive HAART to maintain a viral load as low as possible, regardless of CD4 count. This study will compare the times to development of high-grade anal dysplasia or anal cancer in participants who are currently enrolled in the SMART study.

Patients will participate in this substudy and the main SMART study at the same time. At the baseline visit, participants will undergo an anal swab; some female participants will have a cervical swab as well. Participants will provide a detailed sexual history including sexually transmitted infections, a history of anal-related conditions, and a history of alcohol and recreational drug use. These procedures will be repeated at each annual follow-up visit. Some participants may undergo additional anal cytology and high-resolution anoscopy with biopsy. Participants will be followed until they develop high-grade anal dysplasia or anal cancer or when the SMART study closes, whichever comes first.

• Study Type: Observational
• Enrollment: 560

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90028
      • LA Gay & Lesbian Community Service Ctr., Lamba Med. Group CRS
    • San Francisco, California, United States, 94114
      • Castro-Mission Health Ctr. CRS
  • Colorado
    • Denver, Colorado, United States, 80204-4507
      • Univ. of Colorado Health Science Ctr. CRS
    • Denver, Colorado, United States, 80205
      • Eastside Family Health Ctr. CRS
  • District of Columbia
    • Washington, District of Columbia, United States, 20422
      • Washington DC VAMC, Washington Regional AIDS Program, Infectious Diseases CRS
  • Florida
    • Jacksonville, Florida, United States, 32206
      • Univ. of Florida, Div. of Infectious Diseases CRS
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • CRI-Boston CRS
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hosp. CRS
  • New York
    • New York, New York, United States, 10037-1802
      • Harlem Hospital Ctr./Columbia University CRS (Gordin CTU)
  • Oregon
    • Portland, Oregon, United States, 97227
      • Kaiser Immune Deficiency Clinic of Portland CRS
    • Portland, Oregon, United States, 97239
      • Oregon Health & Sciences Univ. Internal Medicine (L-475) CRS
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Temple Univ. School of Medicine CRS
  • Texas
    • Houston, Texas, United States, 77030
      • Houston AIDS Research Team CRS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 13 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Coenrollment in the SMART study
• Normal anal cytology result. If baseline anal cytology is abnormal, high-resolution anoscopy must be performed and specimens must be obtained.
• Parent or guardian willing to provide informed consent, if applicable

Exclusion Criteria:

• Current or prior history of anal or cervical cancer
• Permanent or irreversible bleeding disorder that would interfere with biopsy of the anal canal

Study Plan

How is the study designed?

Design Details

• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time to high-grade anal dysplasia or anal cancer

Secondary Outcome Measures

Outcome Measure
Time to anal cancer
time to low-grade or high-grade anal dysplasia
time to anal HPV infection
time to anal HPV infection with a specific strain, for types 16, 18, or 31
time to cervical HPV infection
time to cervical HPV infection with a specific strain, for types 16, 18, or 31
time to high-grade anal dysplasia
time from low-grade anal dysplasia to normal

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Study Chair: Calvin Cohen, MD, MSc, Community Research Initiative of New England

Publications and helpful links

General Publications

• Panther LA, Schlecht HP, Dezube BJ. Spectrum of human papillomavirus-related dysplasia and carcinoma of the anus in HIV-infected patients. AIDS Read. 2005 Feb;15(2):79-82, 85-6, 88, 91.
• Heard I, Palefsky JM, Kazatchkine MD. The impact of HIV antiviral therapy on human papillomavirus (HPV) infections and HPV-related diseases. Antivir Ther. 2004 Feb;9(1):13-22.
• Piketty C, Darragh TM, Da Costa M, Bruneval P, Heard I, Kazatchkine MD, Palefsky JM. High prevalence of anal human papillomavirus infection and anal cancer precursors among HIV-infected persons in the absence of anal intercourse. Ann Intern Med. 2003 Mar 18;138(6):453-9. doi: 10.7326/0003-4819-138-6-200303180-00008.
• Manzione CR, Nadal SR, Calore EE. [Human papillomavirus oncogenicity and grade of anal intraepithelial neoplasia in HIV positive patients]. Rev Assoc Med Bras (1992). 2004 Jul-Sep;50(3):282-5. doi: 10.1590/s0104-42302004000300035. Epub 2004 Oct 21. Portuguese.

Helpful Links

• Click here for more information on CPCRA 065

Study record dates

Study Major Dates

• Study Start: February 1, 2005
• Primary Completion (Actual): March 1, 2006
• Study Completion (Actual): March 1, 2006

Study Registration Dates

• First Submitted: April 6, 2005
• First Submitted That Met QC Criteria: April 6, 2005
• First Posted (Estimate): April 7, 2005

Study Record Updates

• Last Update Posted (Estimate): April 17, 2014
• Last Update Submitted That Met QC Criteria: April 15, 2014
• Last Verified: April 1, 2014

More Information

Terms related to this study

• Keywords: Antiretroviral Therapy, Highly Active; HIV; Treatment Experienced; HPV; Papillomavirus, Human
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Anus Diseases; Anus Neoplasms
• Other Study ID Numbers: CPCRA 065G; SMART; 10117 (DAIDS-ES)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No