Clinical trial NCT00107679: A Study of Anal Cancer Development in HIV Infected People
Official title: Anal Dysplasia: A Substudy of a Large, Simple Trial Comparing Two Strategies for Management of Anti-Retroviral Therapy (The SMART Study)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV Infections
Anus Neoplasms
Keywords: Treatment Experienced
HIV
HPV
Antiretroviral Therapy, Highly Active
Papillomavirus, Human
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2005-04-07
Enrollment: 560
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Time perspective: PROSPECTIVE

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Time to high-grade anal dysplasia or anal cancer
Secondary outcomes:
measure: Time to anal cancer
measure: time to low-grade or high-grade anal dysplasia
measure: time to anal HPV infection
measure: time to anal HPV infection with a specific strain, for types 16, 18, or 31
measure: time to cervical HPV infection
measure: time to cervical HPV infection with a specific strain, for types 16, 18, or 31
measure: time to high-grade anal dysplasia
measure: time from low-grade anal dysplasia to normal
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: LA Gay & Lesbian Community Service Ctr., Lamba Med. Group CRS
state: California
city: San Francisco
country: United States
facility: Castro-Mission Health Ctr. CRS
state: California
city: Denver
country: United States
facility: Univ. of Colorado Health Science Ctr. CRS
state: Colorado
city: Denver
country: United States
facility: Eastside Family Health Ctr. CRS
state: Colorado
city: Washington
country: United States
facility: Washington DC VAMC, Washington Regional AIDS Program, Infectious Diseases CRS
state: District of Columbia
city: Jacksonville
country: United States
facility: Univ. of Florida, Div. of Infectious Diseases CRS
state: Florida
city: Boston
country: United States
facility: CRI-Boston CRS
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hosp. CRS
state: Michigan
city: New York
country: United States
facility: Harlem Hospital Ctr./Columbia University CRS (Gordin CTU)
state: New York
city: Portland
country: United States
facility: Kaiser Immune Deficiency Clinic of Portland CRS
state: Oregon
city: Portland
country: United States
facility: Oregon Health & Sciences Univ. Internal Medicine (L-475) CRS
state: Oregon
city: Philadelphia
country: United States
facility: Temple Univ. School of Medicine CRS
state: Pennsylvania
city: Houston
country: United States
facility: Houston AIDS Research Team CRS
state: Texas
Study officials:
affiliation: Community Research Initiative of New England
name: Calvin Cohen, MD, MSc
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.