Investigate whether switch from a non-nucleoside reverse transcriptase inhibitor (NNRTI)- or protease inhibitor (PI)-based regimen to a raltegravir-based regimen results in reduced platelet reactivity, reduced platelet-leukocyte aggregate formation…
ID
Source
Brief title
Condition
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
1. Platelet reactivity: platelet expression of the platelet activation marker
CD62P (P-selectin) and activated fibrinogen receptor (αIIbβ3) upon stimulation
with different platelet agonists. 2. Platelet-leukocyte aggregates (eg. PMA).
3. Proportion of CD14+CD16 ++(bright) monocytes compared to CD14+CD16- and
activation state of monocytes (CD11b expression) and lymphocytes (CD38+ HLA-DR+
CD8+ T cells). 4. Soluble (plasma) markers of platelet and monocyte
activation.
Secondary outcome
Investigate whether switch to raltegravir is associated with:
a) reduced activation status of monocytes and of CD4 and CD8 lymphocytes
b) reduced expression of CCR5 on monocytes and CD4+ T-lymphocytes
c) reduced plasma levels of inflammatory markers (eg. hs-CRP, several cytokines)
d) epigenetic changes (eg. Histone methylation)
e) altered IL-32 expression and splicing
Background summary
Cardiovascular disease (CVD) has emerged as a leading cause of morbidity and
mortality in HIV-infected individuals. The precise mechanisms underlying this
increased cardiovascular risk remain to be elucidated . Platelet
hyperreactivity and increased platelet-monocyte aggregation (PMA) are found in
HIV-infected patients and may contribute to the excess cardiovascular risk as
platelets play a key role in the onset and progression of atherosclerosis and
in acute cardiovascular events. In addition, HIV-infected individuals
frequently suffer from persistent immune activation and inflammation. In a
cross-sectional study we recently showed that individuals using a regimen
containing the integrase inhibitor raltegravir have reduced platelet
hyperreactivity and PMA compared to other antiretroviral regimens. Other recent
studies showed that raltegravir is associated with decreased immune activation.
Due to the inherent limitations of cross sectional studies, we aim to expand
our findings in an intervention study.
Study objective
Investigate whether switch from a non-nucleoside reverse transcriptase
inhibitor (NNRTI)- or protease inhibitor (PI)-based regimen to a
raltegravir-based regimen results in reduced platelet reactivity, reduced
platelet-leukocyte aggregate formation and pro-inflammatory status of
monocytes.
Study design
Investigator initiated, single-center, open-label, randomized controlled trial
in HIV-infected patients using a NNRTI- or PI-based regimen
Intervention
Participants will be randomized (1:1) to continue the same ART regimen
(*Continuation group*) or to switch their NNRTI or PI to raltegravir (*Switch
group*) during 10 weeks.
Study burden and risks
Raltegravir is a registered drug for both naïve and treatment experienced
HIV-infected patients. There is extensive clinical experience with this drug
and it has a good safety profile with few side effects. A raltegravir-based
regimen is one of the recommended first line treatment option for HIV-infected
individuals. A possible burden is that raltegravir should be taken twice daily,
whereas some regimens are taken once daily. Participation in this study
involves three extra visits and three extra venipunctures with a total amount
of blood taken for the whole study of approximately 160 mL.
Geert Grooteplein-Zuid 10
Nijmegen 6525 GA
NL
Geert Grooteplein-Zuid 10
Nijmegen 6525 GA
NL
Listed location countries
Age
Inclusion criteria
•Documented HIV-infection
•Age >= 18 years
•On stable antiretroviral therapy (ART) for >= 6 months at screening
•Undetectable plasma HIV viral load (<50 copies/mL) for at least 6 months
•CD4 cell count > 300 cells/mm3 at last measurement
•Current ART regimen at screening consisting of a backbone of two NRTI*s (either TDF/FTC or ABC/3TC) with either a NNRTI (EFV or RPV) or a boosted PI (DRV/r, ATZ/r or LPV/r) and on this regimen for > 3 months
•If female and of childbearing potential using effective birth control methods
Exclusion criteria
•Use of platelet function inhibitors, such as aspirin and ADP receptor antagonists
•Known hypersensitivity to raltegravir or any other component of the formulation
•Using any concomitant therapy disallowed as per SPC for the study drug
•Signs of symptoms of an active (opportunistic) infection other than HIV
•Active hepatitis B or C
•Estimated glomerular filtration rate (by MDRD) <50 ml/min
•History of suspected or proven virologic failure since ART initiation (HIV-1 RNA *blips* less than 500 copies per milliliter with subsequent resuppression are allowed)
•Known genotypic resistance to any current ART component
•In females, pregnancy or breast feeding
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT02383355 |
| CCMO | NL50681.091.14 |