Clinical trial NCT01453933: RAltegravir Switch STudy: Effects on Endothelial Recovery
Official title: Phase IV, Randomized, Open Label, Crossover, Intervention Trial to Investigate the Effect of the Switch of Lopinavir/Ritonavir to Raltegravir on Endothelial Function, Chronic Inflammation, Immune Activation and HIV Replication <50 Copies/ml
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: HIV Infection
Endothelial Dysfunction
Keywords: Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Lopinavir/ritonavir
Lead sponsor: UMC Utrecht
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2011-10-18
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Treatment with HIV-infection with protease inhibitors is associated with high blood lipids and higher chance for cardiovascular complications. The RASSTER study aims to investigate the effect of switching the protease inhibitor lopinavir/ritonavir to raltegravir on vessel wall function and inflammation,and activation of the immune system. we hypothesize that with this intervention these parameters will improve. Since decreased vessel wall function and inflammation are initial steps in the process of atherosclerosis, it is important to know this data when treating HIV-infected patients.

Detailed description: Fixed dose combination lopinavir/ritonavir (LPV/r) is a widespread used antiretroviral drug belonging to the class of protease inhibitors (PIs). PIs are associated with an increased risk of myocardial infarction. However, data is available suggesting increased levels of plasma lipids are not the sole explanation for this observation. Treatment with LPV/r might lead 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 LPV/r to raltegravir in HIV-infected patients with suppressed plasma viral load (\<50 copies/ml) will lead to an improvement of endothelial function.

Objective:

* First, to assess the effect of the switch of lopinavir/ritonavir to raltegravir on endothelial function.
* Second, 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.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years
* HIV-1 infection
* Treatment with antiretroviral regimen containing lopinavir/ritonavir for at least the previous 3 months
* No other protease inhibitors besides lopinavir/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 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

Primary outcomes:
measure: Change in flow mediated dilatation (FMD) of the brachial artery
timeFrame: week 8, week16
Secondary outcomes:
measure: Change in markers of chronic inflammation
timeFrame: Baseline, week 2, week 4, week 8, week 10, week 12 and week 16
measure: Change in markers of immune activation
timeFrame: Baseline, week 2, week 4, week 8, week 10, week 12 and week 16
measure: Change in markers of endothelial function
timeFrame: Baseline, week 2, week 4, week 8, week 10, week 12 and week 16
measure: Changes in plasma HIV-RNA below 50 copies/ml
timeFrame: Baseline, week 8, week 16
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Onze Lieve Vrouwe Gasthuis
state: Noord Holland
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
Study officials:
affiliation: University Medical Center Utrecht, The Netherlands
name: Andy IM Hoepelman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University Medical Center Utrecht, The Netherlands
name: Steven FL van Lelyveld, MD
role: STUDY_DIRECTOR
References:
citation: Krikke M, Tesselaar K, van den Berk GEL, Otto SA, Freriks LH, van Lelyveld SFL, Visseren FJL, Hoepelman AIM, Arends JE. The effect of switching protease inhibitors to raltegravir on endothelial function, in HIV-infected patients. HIV Clin Trials. 2018 Apr;19(2):75-83. doi: 10.1080/15284336.2018.1455366.