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

NCT ID: NCT06640192

Last Updated: 2025-06-25

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-05-30
• Study Completion Date: 2027-01-31

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.

Detailed Description

Data on the penetration of antiretrovirals into the tissues of long-term treated HIV patients are very limited. Previous pharmacokinetic studies indicate that tissue concentrations of the drug are much lower than those observed in plasma of HIV-infected patients or healthy volunteers. In addition, another study has reported that intracellular levels of antiretrovirals are much lower in lymphoid tissues than in peripheral blood after 6 months of TAR initiation, and these levels correlated inversely with ongoing viral replication.

In the line of research that we are raising, a previous study has reported a decrease in intracellular HIV RNA in lymphoid tissue when dolutegravir was administered at higher than usual doses. This is an important advance and new studies should be implemented with a design that allows to potentiate this strategy and significantly decrease the size of the viral reservoir in tissues.

If the hypothesis of the project, which consists mainly in the reduction or elimination of the HIV reservoir, is demonstrated, there would be very important consequences in the area of functional cure of HIV and/or reduction of chronic persistent inflammation, which could generate changes in conventional treatment schemes with great scalability. In addition, it is possible that by decreasing levels of persistent viral replication, an improvement in levels of immune activation and inflammation may also be observed, which would contribute positively to the overall health of the patient. Oral antiretroviral medication is proposed in order to compound a three-drug antiretroviral regimen. The three antiretroviral drugs have been chosen because they are the only ones that allow administration at higher doses without causing increased toxicity: dolutegravir 50 mg/12 h, maraviroc 300 mg/12 h and lamivudine 300 mg/12 h.

Conditions

HIV-1-infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Control

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

Group Type: ACTIVE_COMPARATOR

Standardised triple antiretroviral therapy

Intervention Type: 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.

Intervention

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

Group Type: EXPERIMENTAL

High doses Triple therapy antiretroviral drugs

Intervention Type: DRUG

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

Interventions

Standardised triple antiretroviral therapy

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.

Intervention Type: DRUG

High doses Triple therapy antiretroviral drugs

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.
• Undetectable plasma viral load (<50 copies of HIV RNA in blood plasma) for at least 12 months prior to inclusion.
• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Santiago Moreno Guillen

Role: PRINCIPAL_INVESTIGATOR

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

Locations

Hospital Universitario Ramón y Cajal

Madrid, Madrid, Spain

Site Status: NOT_YET_RECRUITING

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status: RECRUITING

Countries

Spain

Central Contacts

Santiago Moreno Guillen, PhD

Role: CONTACT

smguillen@salud.madrid.org

91 336 87 10

Erick de la Torre

Role: CONTACT

erick.delatorretarazona@gmail.com

Facility Contacts

Maria de Lagarde Sebastián

Role: primary

estudioshiv12@gmail.com

Other Identifiers

DOSAGE

Identifier Type: -

Identifier Source: org_study_id