Acceptability and Feasibility of Combination Treatment for Cervical Precancer Among South African Women Living With HIV (ACT2)

Acceptability and Feasibility of Combination Treatment for Cervical Precancer Among South African Women Living With HIV

Acceptability and Feasibility of Combination Treatment for Cervical Precancer Among South African Women Living With HIV

The purpose of this study is to explore whether an anti-cancer medication (5-fluorouracil cream) placed in the vagina after a surgical excision procedure is an acceptable and useful form of treatment for cervical precancer among the woman with HIV infection.

There are currently no medical therapies recommended to promote the clearance of humanpapilloma virus (HPV) infection, regression of cervical dysplasia, or treatment of cervical intraepithelial neoplasia (CIN). Human immunodeficiency virus (HIV) -infected women are at higher risk of HPV infection, with rates as high as 45% - 90%. Despite being preventable, cytologic abnormalities, cervical precancer (high-grade cervical intraepithelial neoplasia [CIN2/3]), and invasive cervical cancer also occur more frequently in HIV infected women. This study is testing whether topical 5-fluorouracil (5FU) can be used as a patient-controlled adjuvant treatment for cervical precancer (CIN2/3) to be self-administered after surgical excision to reduce the risk of persistent/recurrent CIN2/3 and progression to cervical cancer among HIV-infected women.

The feasibility of the combination of surgical excision followed by adjuvant 5FU for the treatment of CIN2/3 among HIV-infected women will be evaluated using the number of subjects adhered to and retained in the study.

The acceptability of the combination of surgical excision followed by adjuvant 5FU for the treatment of CIN2/3 among HIV-infected women will be assessed through a participant questionnaire administered at midline and end of the study.

Efficacy of combination treatment for CIN2/3 will be assessed as the number of subjects with CIN2 or CIN3 regressed to CIN1 or normal histology.

Efficacy of combination treatment for HPV will be assessed as the percentage of women in each study arm who demonstrate clearance of high-risk HPV between baseline and 24 weeks.

Inclusion Criteria: Confirmed HIV-1 infection On antiretroviral therapy (ART), for at least 90 days prior to enrollment Cervical biopsy demonstrating CIN2/3 within the preceding 120 days. Exclusion Criteria: pregnancy, breastfeeding, intend to become pregnant within 180 days of enrollment have an active sexually transmitted infection (women may participate once treated) have a surgically absent cervix have a history of anogenital (cervical, vaginal, vulvar, or anal) cancer or a biopsy suspicious for cervical cancer have a medical comorbidity that would interfere with study participation.

The rights and privacy of individuals who participate in research will be protected at all times. Thus, data intended for broader use will be stripped of identifiers that would permit linkages to individual research participants or variables that could lead to deductive disclosure of the identity of individual subjects. Research data that documents, supports and validates research findings will be made available after the main findings from the final research dataset have been accepted for publication. Such research data will be redacted to prevent the disclosure of personal identifiers. All data sharing will abide by rules and/or policies defined by the sponsor, relevant IRBs, U.S. local, state, and federal laws and regulations, as well as South African laws and regulations.