Effects of ART Simplification on Inflammatory Markers in CoRis (AIR)

NCT ID: NCT03501719

Last Updated: 2025-03-17

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 177 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-03-01
• Study Completion Date: 2022-03-01

Brief Summary

The effects of the number of drugs included in antiretroviral therapy (ART) regimens of inflammatory markers remains undefined. We will evaluated in participants in the Spanish AIDS Research Network, whether triple ART, dual ART or monotherapy affect differentially the dynamics of inflammatory markers.

Detailed Description

During treated HIV infection, higher levels of the inflammatory and coagulation markers interleukin-6 (IL-6), D-dimers, and high-sensitivity C-reactive protein (hs-CRP) are associated with an increased risk of cardio-vascular disease (CVD), cancer, and all-cause mortality. While ART decreases IL-6, D-dimer and hs-CRP levels, these biomarkers remain elevated relative to the general population even when the plasma HIV RNA is suppressed. Markers of inflammation and coagulation have been widely studied in the general population, and related to higher risk of CVD, cancer, kidney function decline and all-cause mortality. These data collectively suggest that chronic inflammation and/or hyper-coagulation contribute to the pathogenesis of these serious non-AIDS events during otherwise effective ART. Given the assumed, albeit unproven, role of these pathways in causing disease, both vascular and non-vascular, there is intense interest in studying interventions that reduce inflammation and/or coagulation.

Recent simplification strategies have demonstrated that once HIV RNA suppression is achieved, the extent of virological control does not appear to depend so much on the number of drugs, but on the time of HIV RNA suppression before the simplification. In fact, some simplification therapies, including dual regimens based in boosted-protease inhibitors (PI) have proved to be non-inferior to triple ART, provided that drug resistance has been excluded. More recently, dual therapies based in other combinations not based in boosted-PI have emerged as viable therapeutic strategies.

While these approaches of ART simplification seems to be non-inferior to standard triple therapy in terms of short-term plasma HIV RNA suppression and CD4+ T cell count dynamics, it is unknown whether ART simplification will prove safe in the long term. Mounting evidence support that the concentration of drugs, which may be related to the number of drugs, affects the extent of virological control in the tissues in which HIV persists and replicates, generating low-level viremia and contributing to chronic inflammation. It is likely that clinical trials powered to detect differences in clinical events will not be performed. Hence, the long-term clinical efficacy of ART simplification must be assessed in cohort studies and the long-term effects on inflammatory markers that independently predict mortality must be assessed.

Conditions

HIV

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

Triple ART

Patients who remain in triple ART during the follow-up.

Number of drugs in the ART regimen

Intervention Type: DRUG

Triple therapy vs. dual therapy vs. monotherapy

Dual ART

Patients switched to dual ART during the follow-up.

Number of drugs in the ART regimen

Intervention Type: DRUG

Triple therapy vs. dual therapy vs. monotherapy

Monotherapy

Patients switched to monotherapy during the follow-up.

Number of drugs in the ART regimen

Intervention Type: DRUG

Triple therapy vs. dual therapy vs. monotherapy

Interventions

Number of drugs in the ART regimen

Triple therapy vs. dual therapy vs. monotherapy

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Subjects initiating ART in CoRIS from 2004 with triple therapy.
• HIV RNA suppression achieved in the first 48 weeks of ART.

Exclusion Criteria

• ART initiation with regimens with less than three drugs
• Virologic failure in the first 48 weeks of ART
• AIDS conditions or serious non-AIDS events in the first 48 weeks of ART.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 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

Locations

Hospital Ramón y Cajal

Madrid, , Spain

Countries

Spain

Other Identifiers

133-17

Identifier Type: -

Identifier Source: org_study_id