Title
A Phase I Study of Intra-anally Administered Lopinavir/Ritonavir in People Living with HIV (PLWH) with High-Grade Anal Intraepithelial Neoplasia (AIN 2/3)

Description
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 study for approximately 3 months.
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.

Objective
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

Treatment 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 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.

Key Eligibility Inclusion Criteria:

willing to provide informed consent

greater than or equal to 18 years of age

Human papillomavirus (HPV) positive

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

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

Applicable Disease Sites
Anal

Participating Institutions
UW Health Digestive Health Center; UW Health Eastpark Medical Center; UW Health University Hospital