Administration of High Doses of Antiretroviral Drugs to Eliminate the Latent HIV-1 Reservoir

NCT06640192 | Recruiting Phase 2

• 1 other identifier: DOSAGE
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 2

Brief Summary

The HIV epidemic represents one of the greatest health challenges worldwide, with important social and economic implications for public health. Although combination antiretroviral therapy (TAR) is effective in controlling infection and delaying disease onset, as well as improving the quality of life of infected persons, the relevant medical needs caused by HIV-1 infection are not yet fully met by TAR. The main obstacle to curing HIV is the establishment and maintenance of the viral reservoir. Therefore, we believe that this clinical trial will provide knowledge, for the first time, of the increase of antiretroviral drug levels in lymphatic tissue achieved by simultaneous administration of antiretroviral drugs at higher than usual doses, and their effect on persistent viral replication in intestinal lymphatic tissue and, as a consequence, on the latent cellular reservoir of HIV.

Conditions

HIV-1-infection

Outcome Measures

Primary Outcomes (1)

• To evaluate the variation in the size of the latent cellular reservoir of HIV-1 in lymphoid tissue and peripheral blood after administration of high doses of antiretroviral drugs.

  Latent cell reservoir size by measuring total and intact proviral DNA (IPDA).

  48 weeks

Secondary Outcomes (6)

• To evaluate the variation of intracellular HIV RNA in total CD4+ T cells and memory phenotypes from baseline to weeks 24 and 48 in both blood and lymphoid tissue.

  48 weeks

• To compare changes in distribution and activation markers ( CD25, HLA-DR among others) in T-cell subpopulations (naïve and memory phenotypes).

  48 weeks

• To evaluate the effects of the intervention on markers of inflammation and bacterial translocation.

  48 weeks

• To determine antiretroviral drug concentrations in blood and gastrointestinal tract tissue.

  48 weeks

• To correlate markers of viral persistence (intact HIV DNA and ca-HIV RNA) with drug concentrations, as well as with activation and inflammation parameters of cell subpopulations and plasma.

  48 weeks

Study Arms (2)

Control

ACTIVE COMPARATOR

Triple therapy antiretroviral drugs on their usual regimen containing an integrase inhibitor

Drug: Standardised triple antiretroviral therapy

Intervention

EXPERIMENTAL

High doses of triple therapy antiretroviral drugs: dolutegravir 50 mg/12 h, maraviroc 300 mg/12 h and lamivudine 300 mg/12 h.

Drug: High doses Triple therapy antiretroviral drugs

Interventions

Standardised triple antiretroviral therapy DRUG

patients have to use Triple therapy antiretroviral drugs on their usual regimen containing an integrase inhibitor. There are many types of drugs within this group, so they are not specified.

Control

High doses Triple therapy antiretroviral drugs DRUG

dolutegravir 50 mg/12 h, maraviroc 300 mg/12 h and lamivudine 300 mg/12 h

Intervention

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients who, after receiving information about the study design, the aims of the study, the possible risks that may arise from it and the fact that they can refuse to collaborate at any time, give written consent to participate in the study.
• Be over 18 years of age and under 60 years of age.
• Understand the purpose of the study and be available to perform the visits and procedures established in the protocol.
• Persons with HIV being followed up in HIV consultations.
• Antiretroviral treatment with a triple regimen containing an integrase inhibitor.
• No history of prior virologic failure.
• No known gastrointestinal disease.
• R5 viral tropism, determined on proviral DNA.
• In women: negative urine pregnancy test performed within 7 days prior to the start of study treatment in women of childbearing age and if \< 2 years post menopause.
• Women of childbearing age and male partners of childbearing age must agree to use a highly effective method of contraception (such as surgical sterilization, double barrier method, oral contraceptives, or hormonal contraceptive implants) and to continue using them until 6 months after the last dose of treatment.

You may not qualify if:

• Chronic Hepatitis B (HBsAg +)
• Untreated chronic hepatitis C
• Viral tropism X4
• Pregnancy or planning to become pregnant during the course of the study.
• Lactation.
• Abnormal coagulation parameters (PT\> or equal to 1.2 LSN).
• Thrombocytopenia (platelet count \<50000).
• Transaminases in values greater than 3 times normal.
• Impaired renal function (plasma creatinine \>1.5 mg/dl, creatinine clearance \<60 ml/min/1.73 m2).
• Contraindications for the performance of any of the study procedures (colonoscopy/bowel biopsy) or conscious sedation.
• Anemia (greater than or equal to grade 1).
• Administration of aspirin, ibuprofen, warfarin or other agents that interfere with the coagulation cascade are prohibited 1 week before endoscopy.
• Concomitant treatment with cytochrome CYP3A inducers or inhibitors.
• Patients in whom there is a contraindication for use according to the established in the technical data sheet or known hypersensitivity to the drugs under investigation or who, according to the investigator's criteria, it is not advisable to participate.

Sponsors & Collaborators

• Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal: lead

Study Sites (2)

Hospital Universitario Ramón y Cajal

Madrid, Madrid, 28034, Spain

NOT YET RECRUITING

Hospital Universitario 12 de Octubre

Madrid, Spain

RECRUITING

Study Officials

• Santiago Moreno Guillen

  IRYCIS. Hospital Universitario Ramón y Cajal. Madrid, Spain.

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Santiago Moreno Guillen, PhD

CONTACT

91 336 87 10; smguillen@salud.madrid.org

Erick de la Torre

CONTACT

erick.delatorretarazona@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2024
• First Posted: October 15, 2024
• Study Start: May 30, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: June 25, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (2)