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Randomized Controlled Trial
. 2012 Nov 1;61(3):317-25.
doi: 10.1097/QAI.0b013e31826e7d0f.

A randomized controlled trial assessing the effects of raltegravir intensification on endothelial function in treated HIV infection

Hiroyu Hatano  1 , Rebecca Scherzer, Yuaner Wu, Kara Harvill, Kristinalisa Maka, Rebecca Hoh, Elizabeth Sinclair, Sarah Palmer, Jeffrey N Martin, Michael P Busch, Steven G Deeks, Priscilla Y Hsue
Affiliations
Randomized Controlled Trial

A randomized controlled trial assessing the effects of raltegravir intensification on endothelial function in treated HIV infection

Hiroyu Hatano et al. J Acquir Immune Defic Syndr. .

Abstract

Objectives: To determine whether intensification with raltegravir improves endothelial function in antiretroviral-treated HIV-infected individuals.

Design: : Randomized, double-blinded, placebo-controlled study.

Methods: Fifty-six subjects with treatment-mediated viral suppression for at least 1 year were randomized to add 400 mg of raltegravir twice daily or matching placebo for 24 weeks. The primary endpoint was the difference in rate of change in endothelial function [as assessed by flow-mediated vasodilation (FMD) of the brachial artery] from baseline to week 24 between the raltegravir and placebo groups. Linear mixed models were used to evaluate the association of treatment group with changes in FMD, immune activation, and measures of viral persistence.

Results: At baseline, the median CD4 T-cell count was 498 cells/mm, nadir CD4 T-cell count was 191 cells/mm, duration of HIV infection was 18 years, FMD was 3.3%, and hyperemic velocity (a marker of microvascular function) was 68.3 cm. There were no significant differences between treatment groups in rate of change in FMD (raltegravir group: +0.032% per week, placebo group: +0.023% per week; P = 0.60). There were also no differences between treatment groups in rate of change in hyperemic velocity, immune activation, or viral persistence. In multivariable analysis, older age, longer duration of HIV infection, and current abacavir use were associated with lower FMD. Lower CD4 T-cell count and current abacavir use were associated with lower hyperemic velocity.

Conclusions: The addition of raltegravir to suppressive antiretroviral therapy did not have a significant impact on cardiovascular risk, as assessed by endothelial function (ClinicalTrials.gov NCT00843713).

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Conflict of interest statement

CONFLICTS OF INTEREST

RS, YW, KH, KM, RH, ES, SP, JNM, MPB, PYH: No conflicts.

Figures

FIGURE 1
FIGURE 1. Study schema
56 HAART- suppressed subjects added raltegravir 400 mg twice daily or matching placebo to their current suppressive HAART regimens for 24 weeks. 32/56 subjects were “immunologic responders” (CD4+ ≥350 cells/mm3 and viral suppression for ≥1 year). The remaining subjects (24/56) were “immunologic non-responders” (CD4+ <350 cells/mm3 for ≥1 year despite viral suppression for ≥1 year) ; 22/24 of the immunologic non-responders continued study participation in an extension study in which all 22 subjects received open-label raltegravir from weeks 24 to 48. Of these 22 subjects, 6 subjects chose to continue raltegravir indefinitely (through week 60). HAART=highly active antiretroviral therapy. FMD=flow-mediated vasodilation.
FIGURE 2
FIGURE 2
FIGURE 2A. Flow-mediated vasodilation (FMD) by study week and treatment group. P-values denote differences in FMD between treatment groups. FIGURE 2B. Hyperemic velocity by study week and treatment group. P-values denote differences in hyperemic velocity between treatment groups.
FIGURE 2
FIGURE 2
FIGURE 2A. Flow-mediated vasodilation (FMD) by study week and treatment group. P-values denote differences in FMD between treatment groups. FIGURE 2B. Hyperemic velocity by study week and treatment group. P-values denote differences in hyperemic velocity between treatment groups.
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