1. To assess the effect of the switch from protease inhibitors to raltegravir on endothelial function. 2. To assess the effect of the intervention mentioned above on markers of endothelial function; immune activation; chronic inflammation; and, on…
ID
Source
Brief title
Condition
- Viral infectious disorders
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Change in flow-mediated dilatation (FMD) of the brachial artery after 8 weeks
of raltegravir treatment (compared to treatment with protease inhibitors).
Secondary outcome
-Change in endothelial function measured by EndoPAT
-change in markers of endothelial function
-change in markers of chronic inflammation
-change in markers of immune activation
-change in plasma HIV-RNA below 50 copies/ml
Background summary
Lopinavir-ritonavir (LPV/r) and atazanavir/ritonavir (ATZ/r) are widespread
antiretroviral drugs belonging to the class of protease inhibitors (PIs). PIs
are associated with an increased risk of myocardial infarction. However, data
is available suggesting that increased levels of plasma lipids are not the sole
explanation for this observation. We hypothesize that treatment with LPV/r or
ATZ/r leads to a decrease of endothelial function as well, thus explaining the
increased risk of myocardial infarction besides increased plasma lipids.
Raltegravir is a registered antiretroviral drug with no known cardiovascular
side effects. We hypothesize that switching of LPV/r or ATZ/r to raltegravir in
HIV-infected patients with suppressed plasma viral load (<50 copies/ml) will
lead to an improvement of endothelial function.
Study objective
1. To assess the effect of the switch from protease inhibitors to raltegravir
on endothelial function.
2. To assess the effect of the intervention mentioned above on markers of
endothelial function; immune activation; chronic inflammation; and, on plasma
HIV-RNA below the cut-off of 50 copies/ml.
Study design
Phase IV, randomised, open label, cross-over, intervention trial.
Intervention
Randomisation into two arms: A and B. In arm A, LPV/r or ATZ/r will be switched
to raltegravir, while study subjects in arm B will continue their LPV/r or
ATZ/r-containing regimen. After 8 weeks, cross-over of the study arms will be
performed. Subjects in arm A will then switch back to LPV/r or ATZ/r, while
subjects in arm B will then switch to raltegravir. The total duration of the
study is 16 weeks. Raltegravir has to be taken twice daily.
Study burden and risks
Study duration is 16 weeks, consisting of 8 visits. Assuming HIV-infected
patients are monitored every three months, there will be approximately 6 extra
visits. Endothelial function will be measured by FMD three times
(non-invasively, combined), each visit blood will be drawn for assessment of
the level of chronic inflammation, immune activation and virological studies.
Complete physical examination will be performed at screening visit. Vital
parameters and weight measurement will be performed on every visit. There seems
low risk when participating in this study, since the study medication is
approved and registered, currently known side effects of raltegravir are
minimal, duration of treatment with study medication is short (8 weeks) and
patients will be monitored frequently. With this study we hope to gain more
insight into the mechanism of increased risk of myocardial infarction in
patients treated with protease inhibitors.
Heidelberglaan 100
Utrecht 3508 GA
NL
Heidelberglaan 100
Utrecht 3508 GA
NL
Listed location countries
Age
Inclusion criteria
-Age >= 18 years
-HIV-1 infection
-Treatment with antiretroviral regimen containing lopinavir/ritonavir or atazanavir/ritonavir for at least the previous 3 months
-No other protease inhibitors besides lopinavir-ritonavir or atazanavir/ritonavir in antiretroviral regimen
-Subjects must have a minimum period of viral suppression (plasma HIV-RNA <50 copies/ml) of 6 months
-Subjects will not have a history of virological failure on antiretroviral therapy
-Results of previous resistance testing allowing replacement of lopinavir-ritonavir or atazanavir/ritonavir by raltegravir
-CD4+ cell count > 200 cells/µL
-Signed informed consent
Exclusion criteria
-Pregnancy
-Breastfeeding
-Raltegravir hypersensitivity
-Treatment of underlying malignancy
-Renal insufficiency requiring dialysis
-Acute or decompensated chronic hepatitis (Child-Pugh score C)
-Modification of antiretroviral regimen in the previous 3 months
Design
Recruitment
Medical products/devices used
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 |
|---|---|
| EudraCT | EUCTR2011-003298-26-NL |
| CCMO | NL37593.041.11 |