Clinical trial NCT03501719: Effects of ART Simplification on Inflammatory Markers in CoRis (AIR)
Official title: Effects of ART Simplification on Inflammatory Markers in CoRis (AIR)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: HIV
Keywords: HIV
inflammation
antiretroviral therapy
cohort studies
mortality
non-AIDS events
Lead sponsor: Fundacion para la Investigacion Biomedica del Hospital Universitario Ramon y Cajal
Sponsor class: OTHER
First posted: 2018-04-18
Enrollment: 177
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: HIV-infected patients

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.

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.

Primary outcomes:
measure: Inflammation
timeFrame: From baseline through study completion, an average of 3 years
Secondary outcomes:
measure: Immune activation
timeFrame: From baseline through study completion, an average of 3 years
measure: Coagulation
timeFrame: From baseline through study completion, an average of 3 years
measure: Gut epithelial integrity
timeFrame: From baseline through study completion, an average of 3 years
measure: Monocyte activation/bacterial translocation
timeFrame: From baseline through study completion, an average of 3 years
measure: Immunological variables
timeFrame: From baseline through study completion, an average of 3 years
measure: Comorbidities
timeFrame: From baseline through study completion, an average of 3 years
measure: Period
timeFrame: Baseline
measure: ART history
timeFrame: From baseline through study completion, an average of 3 years
measure: Available virological information
timeFrame: From baseline through study completion, an average of 3 years
measure: ART exposure
timeFrame: From baseline through study completion, an average of 3 years
measure: Sociodemographics
timeFrame: At baseline
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Hospital Ramón y Cajal
Study officials:
References: