Cardiovascular disease and protease inhibitors

2018-06-28

The Data collection on Adverse Events of Anti-HIV Drugs (D:A:D) study consists of 11 different cohorts. In the present study 35,711 HIV-positive individuals were included and followed from 2009 until 2016 or until 6 months after a cardiovascular event. During a median follow-up time of 6.96 years 1,157 persons developed cardiovascular disease (5.34 events per 1,000 person-years). Patients with ritonavir-boosted darunavir had a progressive increased rate of cardiovascular disease. The incidence increased from 4.91 events per 1,000 person years in those who were unexposed to darunavir to 13.67 events in those exposed for more than 6 years. The corresponding figures for atazanavir were posed 5.03 in unexposed and 6.68 in those who were exposed for more than 6 years.

Ryom et al. Lancet HIV 2018;Published on line May 3 doi.org/10.1016/S2352-3018(18)30043-2

Comment: The study shows that the cumulative use of ritonavir-boosted darunavir is associated with an increased risk of cardiovascular disease that is not observed with ritonavir-boosted atazanavir. One has to remember that this is an observational study and not a randomized comparison between different regimens and the results have to be interpreted with caution. When darunavir was introduced it was widely used as a salvage therapy with a higher dose of darunavir and double dose ritonavir. The authors have tried to correct for different potential biases but even so the results have to be interpreted with caution. Presently, darunavir is often boosted with cobicistat instead of ritonavir and different NRTI backbones are used. If those changes would have had any impact on the results is unknown.