NCT05584397

Comparing Immune Activation and Latent HIV Reservoir Size Between People Living With HIV on Tenofovir-containing Versus NRTI-free ART

Comparing Immune Activation and Latent HIV Reservoir Size Between People Living With HIV (PWH) on Tenofovir-containing Versus NRTI-sparing ART

• Status: Enrolling By Invitation
• Phase: —
• Study type: Observational
• Enrollment: 40 (estimated)
• Sponsor: University of Washington · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

The goal of the project is to determine the difference in immune activation and HIV reservoir size between People living with HIV (PWH) on tenofovir-containing antiretroviral therapy (ART) versus PWH on nucleoside reverse transcriptase inhibitor (NRTI)-sparing ART. Tenofovir (TFV), a phosphonated nucleoside reverse transcriptase inhibitor (NRTI), is being used for oral pre-exposure prophylaxis (PrEP). The investigators will test this hypothesis: tenofovir, and perhaps NRTIs in general, stimulate a type I/III interferon also in PWH who take these drugs. Because chronic interferon stimulation may promote the survival and proliferation of cells with integrated provirus, the investigators also hypothesize that these drugs antagonize decay of the HIV latent reservoir in PWH on ART. Consequently, the researchers hypothesize that PWH who have switched from NRTI-containing ART to NRTI-sparing ART exhibit lower type I/III interferon pathway activation and lower latent HIV reservoir size. The investigators also hypothesize that independently of treatment, the extent of type I/III interferon activation correlates with latent HIV reservoir size. Thus, the proposed study seeks to answer these two questions. Can the gastrointestinal epithelium be impacted by ART, and contribute to chronic immune activation and expansion of the HIV-1 reservoir? If so, what therapeutic approaches can the investigators implement to reduce the HIV-1 proviral load? The data will reveal pathways that can be targeted therapeutically to treat chronic immune activation in PWH. The findings of this study will immediately translate to optimize the standard of care in PWH.

Detailed description

The study will be open-label, cross-sectional, two-cohort study (20 participants per cohort will be recruited). Cohort 1: Tenofovir-containing ART (tenofovir disoproxil fumarate \[TDF\] OR tenofovir alafenamide \[TAF\] PLUS any other ART drugs) prescribed for daily use by participants' primary care providers. Cohort 2: NRTI-sparing ART (specifically: rilpivirine PLUS dolutegravir OR rilpivirine PLUS cabotegravir) prescribed for daily use by participants' primary care providers. The investigators plan to test type I/III IFN (interferon) pathway activation using Crystal digital PCR (Crystal-dPCR) to quantify mRNA copy numbers of ISG15 (ISG15 ubiquitin-like modifier), MX1 (MX dynamin like GTPase 1) and IFI6 (interferon alpha inducible protein 6). RNA will be isolated from the rectal and duodenal biopsies stored in RNALater using the RNeasy Fibrous Tissue Mini Kit (Qiagen) and from the PBMC using the RNeasy Plus Mini Kit (Qiagen). Crystal-dPCR will be performed on a 6-color Naica Crystal digital PCR instrument (Stilla Technologies). The latent HIV reservoir will be measured in DNA derived from peripheral blood mononuclear cells (PBMCs) using a novel intact/defective proviral HIV DNA Crystal-dPCR assay developed jointly by the Hladik and Jerome groups in Seattle.

Conditions

• HIV-1-infection
• HIV Disease Progression
• Inflammation
• HIV

Interventions

Type	Name	Description
PROCEDURE	Venipuncture	Draw of peripheral blood (about 20 ml and 40 ml, during the screening and procedure visits, respectively).
PROCEDURE	Targeted physical medical exam	Study participants will be undergoing a physical exam where vitals will be recorded (e.g. temperature, blood pressure, heart rate). The registered nurse (RN) will also perform auscultation of heart and lungs. Study participants will be also asked to fill out a survey with questions related to his/her medical history, current use of medications, sexual history and substance abuse.
PROCEDURE	Urine pregnancy test	Women of childbearing potential will be asked to run an urine pregnancy test during the second (procedure) visit. Pregnant women will not be allowed to participate in the study.
PROCEDURE	Anoscopy	The anoscopy is an examination using a small, rigid, tubular instrument called anoscope (also called an anal speculum). This is inserted a few inches into the rectum in order to collect some small samples of mucosal tissue. We will collect 5 rectum biopsy samples and one cytobrush.
PROCEDURE	Esophagogastroduodenoscopy (EGD)	The EGD involves looking at the esophagus, stomach, and first and second portion of the duodenum. This procedure involves the use of an endoscope to remove small tissue samples. This procedure uses conscious sedation drugs given by a vein in the arm. The procedure takes about 1½-2 hours, including time for recovery. We will collect 5 duodenal biopsies and one cytobrush.

Timeline

• Start date: 2022-09-01
• Primary completion: 2025-06-30
• Completion: 2025-12-28
• First posted: 2022-10-18
• Last updated: 2024-12-05

Locations

1 site across 1 country: United States