Atazanavir and Cardiovascular Risk Among Human Immunodeficiency Virus-Infected Patients: A Systematic Review.
BACKGROUND
Patients with human immunodeficiency virus (HIV) infection have an increased risk of cardiovascular disease (CVD). While viral suppression with antiretroviral therapy decreases CVD risk overall, several studies have suggested that certain antiretrovirals, particularly certain protease inhibitors, may be associated with an increased relative risk of CVD. In AIDS Clinical Trials Group 5260 s, ritonavir-boosted atazanavir (ATV) was associated with slower atherosclerosis progression compared to ritonavir-boosted darunavir and raltegravir, potentially due to hyperbilirubinemia. Although hyperbilirubinemia may lead to increased rates of treatment discontinuation, it may also contribute to a favorable cardiovascular (CV) profile for ATV. To fully elucidate the effect of ATV on CVD risk among HIV-infected patients, a systematic review of the literature was performed.


METHODS
A systematic search of the PubMed and Embase databases was conducted on August 26, 2015, using terms to identify papers that discuss ATV, HIV, and CVD. Articles were limited to English-language publications of randomized-controlled or observational studies investigating adult humans. The primary outcome was the incidence of CVD. Articles describing surrogate markers of CVD were also included.


RESULTS
Ten studies were included in this qualitative analysis: six reported CVD outcomes, two reported data on atherosclerosis as assessed by carotid intima-media thickness (cIMT), and two reported outcomes related to endothelial function. The studies reporting the incidence of myocardial infarction (MI) among HIV-infected patients showed that ATV (boosted and unboosted) was not associated with an increased risk of acute MI. Other CV endpoints were similarly unaffected by treatment with ATV. Compared with non-ATV-based regimens, ATV had beneficial effects on cIMT progression in the publications identified, with no apparent impact on endothelial function.


CONCLUSIONS
This analysis showed that there was no increased risk or occurrence of adverse CV events among HIV-infected patients receiving ATV. Markers of atherosclerosis were improved, suggesting a possible antioxidant effect of ATV, and endothelial function was not affected.


BACKGROUND
Bristol-Myers Squibb (article processing charges and medical writing support).
Hawaii Center for AIDS, John A. Burns School of Medicine, University of Hawaii Mānoa, Honolulu, HI, USA. dominicc@hawaii.edu.
Dominic
D
Chow
Hawaii Center for AIDS, John A. Burns School of Medicine, University of Hawaii Mānoa, Honolulu, HI, USA.
Cecilia
C
Shikuma
Bristol-Myers Squibb, Plainsboro, NJ, USA.
Corey
C
Ritchings
Bristol-Myers Squibb, Plainsboro, NJ, USA.
Muxing
M
Guo
Bristol-Myers Squibb, Plainsboro, NJ, USA.
Lisa
L
Rosenblatt
Antiretroviral therapy; Atazanavir; Atherosclerosis; Cardiovascular disease; Carotid intima-media thickness; Endothelial function; Flow-mediated dilation; HIV; cIMT
J Infect Dis. 2010 Feb 1;201(3):318-30
20039804
Ann Intern Med. 2014 Oct 7;161(7):461-71
25285539
Arterioscler Thromb Vasc Biol. 2011 Feb;31(2):458-63
21088253
N Engl J Med. 2007 Apr 26;356(17):1723-35
17460226
J Gastroenterol Hepatol. 2013 Oct;28(10 ):1643-7
23701650
Am J Med. 2008 Sep;121(9):781-788.e1
18724968
J Epidemiol Community Health. 1998 Jun;52(6):377-84
9764259
Atherosclerosis. 2002 Feb;160(2):449-56
11849670
N Engl J Med. 1999 Jan 7;340(1):14-22
9878640
Ann Med. 2014 May;46(3):138-47
24720602
Clin Infect Dis. 2013 Jul;57(1):112-21
23532479
AIDS. 2010 Aug 24;24(13):2019-27
20613461
N Engl J Med. 2005 Jan 6;352(1):48-62
15635112
AIDS. 2015 Sep 10;29(14 ):1775-83
26372383
J Int AIDS Soc. 2014 Nov 02;17(4 Suppl 3):19544
25394051
PLoS One. 2012;7(9):e44454
22970224
Lancet. 2008 Jul 26;372(9635):293-9
18657708
Clin Infect Dis. 2015 Aug 1;61(3):445-52
25908684
HIV Clin Trials. 2009 Jan-Feb;10(1):1-12
19362991
Vasc Health Risk Manag. 2005;1(3):183-98
17319104
Heart. 2009 Mar;95(5):385-90
18653575
PLoS One. 2013;8(3):e59551
23555704
AIDS. 2010 Nov 27;24(18):2797-801
21063175
Antivir Ther. 2008;13(2):177-87
18505169
Acta Diabetol. 2015 Aug;52(4):709-15
25563478
Epidemiology. 2014 May;25(3):406-17
24713880
AIDS. 2010 Mar 27;24(6):885-90
19952712
Atherosclerosis. 2007 May;192(1):197-203
16762358
Circulation. 2006 Oct 3;114(14):1476-81
17000907
J Acquir Immune Defic Syndr. 2011 Jul 1;57(3):245-53
21499115
J Infect Dis. 2011 Oct 15;204(8):1191-201
21917892
Am Heart J. 2010 Oct;160(4):701-14
20934565
Circulation. 2008 Jul 8;118(2):e29-35
18566319
AIDS. 2013 Jan 28;27(3):407-15
23291539
Clin Infect Dis. 2016 Oct 15;63(8):1122-9
27444412
BMC Infect Dis. 2016 Aug 08;16:376
27503230
AIDS. 2016 Feb 20;30(4):672-4
26825035
HIV Med. 2011 Jul;12(6):374-82
21518220
Clin Chem. 2000 Nov;46(11):1723-7
11067805
J Antimicrob Chemother. 2010 Sep;65(9):1878-88
20554568