Is the risk of myocardial infarction in PLHIV associated with atazanavir or darunavir exposure?
22nd International AIDS Conference, Amsterdam, Netherlands, July 23-27, 2018

Mark Mascolini

Contrary to findings in a recent D:A:D analysis [1], a French case-control comparison found no association of darunavir with myocardial infarction (MI) [2]. Confirming D:A:D results, the French analysis saw no link between atazanavir and MI.

Several studies document a higher MI risk in people with HIV than in the general population. Assessing possible associations between darunavir or atazanavir on cardiovascular disease (CVD) risk, D:A:D study investigators monitored 35,711 HIV-positive adults from January 2009 to February 2016. Adjusting for use of lopinavir, indinavir, or abacavir, they determined that longer use of ritonavir-boosted darunavir independently raised CVD risk (incidence rate ratio 1.59, 95% confidence interval [CI] 1.33 to 1.91 per 5 years of use) [1].

French ANRS investigators conducted a case-control analysis in which cases (in the French Hospital Database on HIV) had a first validated MI between 2006 and 2012 [2]. For each MI case, the researchers selected up to 5 controls with no MI history, matching controls to cases by age, sex, time of MI diagnosis, and clinical center. They used conditional logistic regression models to analyze MI risk per 5 years of exposure to darunavir or atazanavir. This analysis adjusted for antiretroviral exposure, HIV transmission group, sub-Saharan origin, family history of premature coronary artery disease, hypertension, smoking status, current cocaine and/or intravenous drug use, body mass index, viral load, CD4 nadir, and CD4/CD8 ratio before the index data. The researchers conducted a sensitivity analysis adjusting only for use of lopinavir, indinavir, atazanavir, and other nonantiretroviral confounders, as in the D:A:D study.

The analysis included 408 MI cases and 1250 non-MI controls. Both cases and controls had median ages of 49 years, and about 88% were men. Most participants, 81%, had not started antiretrovirals when they enrolled in the French Hospital Database on HIV. The case group had a lower proportion of sub-Saharan African participants (4.4% versus 10.5%,
P = 0.0002) and higher rates of traditional cardiovascular risk factors (smoking, family history of coronary artery disease, hypertension, diabetes, 3 or more cardiovascular risk factors, among others).

Forty-one case patients and 107 controls (10% and 9%) had taken darunavir; 109 cases and 288 controls (27% and 23%) had taken atazanavir.
Multivariable logistic regression analysis identified no association between either darunavir or atazanavir and MI risk. In the analysis adjusted for exposure to other antiretrovirals and other potential confounders, the adjusted odds ratio for darunavir was 0.51 (95% CI 0.11 to 2.32) and for atazanavir 1.54 (95% CI 0.87 to 2.73). The sensitivity analysis adjusting only for lopinavir, indinavir, abacavir, and other nonantiretroviral potential confounders also saw no association between darunavir or atazanavir use and MI risk.

The D:A:D and French studies differ in their endpoint--MI in the French study and cardiovascular disease (MI, stroke, sudden cardiac death, CVD procedures) in D:A:D. The French investigators also noted that they focused on the first occurrence of a validated MI in people with no MI history, whereas D:A:D included people with or without a cardiovascular disease history. The French team wondered whether the association between darunavir and CVD would remain significant in the D:A:D study if D:A:D had accounted for complete antiretroviral history rather than only for lopinavir, indinavir, and abacavir.

1. Ryom L, Lundgren JD, El-Sadr W, et al. Cardiovascular disease and use of contemporary protease inhibitors: the D:A:D international prospective multicohort study. Lancet HIV. 2018;5:e291-e300.
2. Costagliola D, Potard V, Lang S, et al. Is the risk of myocardial infarction in PLHIV associated with atazanavir or darunavir exposure? AIDS 2018: 22nd International AIDS Conference, Amsterdam, Netherlands, July 23-27, 2018. Abstract TUPEB087.