Official Title: “Evaluation of Viral Load Determination and Other Biomarkers of High Risk HPV-Types as a Marker for Progression of Perianal HPV-Infections in HIV-Positive Men Who Have Sex With Men”

Human papillomavirus (HPV)-infection belongs to the most common sexually transmitted diseases worldwide. HIV-infected men having sex with men (MSM) are strongly associated with a higher prevalence of genital HPV-infection, a higher incidence of anal intraepithelial neoplasia (AIN), and, consecutively, an increased risk for anal cancer. Since the introduction of highly active antiretroviral therapy (HAART), the incidence of several viral-associated neoplasias has significantly fallen in HIV-infected individuals. At the beginning of the era of HAART, a justified hope existed that genitoanal HPV-related neoplasias would also decrease based on the success of HAART-induced immune restoration. However, HAART seems to have only a small impact on the natural history of AIN as observed in a cohort of HIV-positive MSM before and after the initiation of HAART.

As AIN and cancer precursor lesions of the cervix, cervical intraepithelial neoplasia, share distinct clinical similarities, cytologic smear testing for AIN has been recommended to detect and treat early lesions. Thus, this prospective study mainly focuses on the predictive value of HPV-DNA load for the development and clinical progression of AIN in HIV-infected MSM. Moreover, the course of HPV viral load under therapy for anal intraepithelial neoplasia, e.g. topical treatment with imiquimod, will be evaluated. Additionally, immunohistochemical determination of several proliferative biomarkers, as well as cytokines, will be performed.

Study Type: Observational

Study Design: Case-Crossover, Prospective

Compared to the general population the incidence of anal intraepithelial neoplasia (AIN) and anal carcinoma (AC) amongst men who have sex with men (MSM) is extremely high (above 70/100,000). While many opportunistic infections have declined since the introduction of highly active antiretroviral therapy (HAART), the incidence of AC has not fallen. In contrast, the HAART-related improvement of survival seems to result in an increased risk of AC in HIV-infected MSM. Screening for cervical intraepithelial neoplasia (CIN) with cervical cytology and early treatment has resulted in a significant decline in the incidence of cervical carcinoma. Like cervical cancer, AC may be preventable through identification and treatment of its precursors. Nevertheless, there has never been an effort to implement an anal cytology screening program for HIV-infected MSM. Persistent cervical infection with high-risk HPV-types is indicative for the development of CIN and cervical cancer. As the prevalence of genital HPV-infections in HIV-infected women and men is very high (up to > 90%), the predictive value of qualitative HPV-DNA detection is limited for cervical cancer or AC prevention. However, several studies have shown that the number of HPV-DNA copies in cervical scrapes may be predictive of the severity of underlying cervical dysplasia. Thus, this prospective study mainly focuses on the predictive value of HPV-DNA load for the development and clinical progression of AIN in HIV-infected MSM.

Besides, HPV-E6/E7-oncogen-expression using RT-PCR will be determined. Moreover, the course of HPV viral load under therapy for anal intraepithelial neoplasia, e.g. topical treatment with imiquimod, will be evaluated. Additionally, immunohistochemical determination of several proliferative biomarkers as well as cytokines will be performed.

Intervention(s) in this Clinical Trial

• Behavioral: Smear and biopsy testing for HPV-types and viral load
  • Smear and biopsy testing for HPV-types and viral load

• Inclusion Criteria: - HIV-infected patients Exclusion Criteria: - None

Gender Eligibility for this Clinical Trial: Male

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Deutsche Luft und Raumfahrt

Overall Clinical Trial Officials and Contacts

Norbert H Brockmeyer, MD Principal Investigator Department of Dermatology, Ruhr University Bochum  

Overall Contact: Norbert H Brockmeyer, MD 0049-234-509-3474 n.brockmeyer@derma.de

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00365729

Study ID Number: 01 KI 0211

ClinicalTrials.gov Identifier: NCT00365729

Health Authority: Germany: Ethics Commission