Overview
This study is being done to assess the safety of lopinavir/ritonavir in patients with PLWH with AIN. 30 participants will be recruited and can expect to be on active study for approximately 3 months and long term follow up for 40 weeks.
Description
This is a Phase I modified 3 + 3 design, in which the maximum tolerated dose (MTD) will be identified. The 3 + 3 dose escalation will consist of 6 dose levels (18 participants; planned escalation described in arms below) in combination with variation in dosing schedules of the drug lopinavir/ritonavir. This design also allows for some possible intermediate doses to be examined if dose-limiting toxicities (DLTs) occur and de-escalation is needed.
An expansion cohort of 12 participants will occur at the MTD. Once the MTD is determined, then secondary outcomes will be evaluated.
Primary Objective
- To evaluate the safety and tolerability of intra-anal administration of lopinavir/ritonavir, administered via suppository with 3 different schedules, in PLWH with high-grade anal intraepithelial neoplasia (HGAIN) (AIN 2/3).
Secondary Objectives
- To measure the effect of intra-anal topical lopinavir/ritonavir administration
- To evaluate clearance of human papillomavirus (HPV)
- To elucidate the mechanism of action of protease inhibitors
Eligibility
Inclusion Criteria:
- willing to provide informed consent
- greater than or equal to 18 years of age
- Diagnosis of biopsy-confirmed HGAIN
- Human immunodeficiency virus (HIV)-positive with CD4 count greater than 200 cells/mm^3 at screening and virologically suppressed on HIV-1 antiretroviral therapy (ART) within last 12 months
- willing to comply with all study procedures
Exclusion Criteria:
- Diagnosis of low-grade anal dysplasia (AIN, low-grade squamous intraepithelial lesion (LSIL)) by HRA.
- CD4 count less than 200 cells/mm^3 at the time of consideration for entry into the study
- unable to provide informed consent
- Pregnant or breastfeeding female
- Currently receiving systemic chemotherapy or radiation therapy for another cancer.
- Lipid profile abnormalities
- total cholesterol greater than 240 mg/dL
- low density lipoproteins (LDL) greater than 160 mg/dL
- high density lipoproteins (HDL) less than 40 mg/dL
- triglycerides greater than 500 mg/dL
- Have received topical therapy for anal dysplasia previously
- Participants who need to take drugs that are contraindicated with lopinavir/ritonavir