Viral Load Determination and Biomarkers of High Risk Human Papillomavirus (HPV) - Types in HIV-positive Men

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00365729
• Other study ID #: 01 KI 0211
• Status: Recruiting
• Phase: N/A
• First received: August 16, 2006
• Last updated: January 20, 2016
• Start date: October 2003
• Est. completion date: January 2018

Study information

• Verified date: January 2016
• Source: Deutsche Luft und Raumfahrt
• Contact: Norbert H Brockmeyer, MD
• Phone: 0049-234-509-3474
• Email: n.brockmeyer[@]derma.de
• Is FDA regulated: No
• Health authority: Germany: Ethics Commission
• Study type: Observational

Clinical Trial Summary

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.

Description:

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-polymerase chain reaction (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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1000
• Est. completion date: January 2018
• Est. primary completion date: January 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• HIV-infected patients

Exclusion Criteria:

Study Design

Observational Model: Case-Crossover, Time Perspective: Prospective

Related Conditions & MeSH terms

• Anal Intraepithelial Neoplasia
• Carcinoma in Situ
• Communicable Diseases
• HIV Infections
• Infection
• Papillomavirus Infections

Intervention

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

Locations

Country	Name	City	State
Germany	Department of Dermatology, Ruhr University Bochum	Bochum	NRW
Germany	Institute of Virology	Köln	NRW

Sponsors (1)

Lead Sponsor	Collaborator
Deutsche Luft und Raumfahrt

Country where clinical trial is conducted

Germany, 

References & Publications (6)

Kreuter A, Brockmeyer NH, Hochdorfer B, Weissenborn SJ, Stücker M, Swoboda J, Altmeyer P, Pfister H, Wieland U. Clinical spectrum and virologic characteristics of anal intraepithelial neoplasia in HIV infection. J Am Acad Dermatol. 2005 Apr;52(4):603-8. — View Citation

Kreuter A, Brockmeyer NH, Pfister H, Altmeyer P, Wieland U; Competence Network HIV/AIDS. Human papillomavirus type 26-associated periungual squamous cell carcinoma in situ in a HIV-infected patient with concomitant penile and anal intraepithelial neoplasi — View Citation

Kreuter A, Brockmeyer NH, Weissenborn SJ, Wafaisade A, Pfister H, Altmeyer P, Wieland U; German Competence Network HIV/AIDS. 5% imiquimod suppositories decrease the DNA load of intra-anal HPV types 6 and 11 in HIV-infected men after surgical ablation of c — View Citation

Kreuter A, Hochdorfer B, Stücker M, Altmeyer P, Weiland U, Conant MA, Brockmeyer NH. Treatment of anal intraepithelial neoplasia in patients with acquired HIV with imiquimod 5% cream. J Am Acad Dermatol. 2004 Jun;50(6):980-1. — View Citation

Kreuter A, Reimann G, Esser S, Rasokat H, Hartmann M, Swoboda J, Conant MA, Tschachler E, Arasteh K, Altmeyer P, Brockmeyer NH. [Screening and therapy of anal intraepithelial neoplasia (AIN) and anal carcinoma in patients with HIV-infection]. Dtsch Med Wochenschr. 2003 Sep 19;128(38):1957-62. Review. German. — View Citation

Kreuter A, Wieland U, Brockmeyer N. [Anal carcinoma and anal intraepithelial neoplasia in HIV-infections]. J Dtsch Dermatol Ges. 2006 Jul;4(7):611-2. German. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Spectrum of HPV types, HPV viral loads, and associated clinical lesions		swabs will be obtained approximately every 6 months	No