AT CROI 2017

SEATTLE (FRONTLINE MEDICAL NEWS) – A study of newer generation protease inhibitors (PIs) suggests that ritonavir-boosted atazanavir (ATV/r) has a better cardiovascular safety profile than ritonavir-boosted darunavir (DRV/r). After adjustment for age and other factors, patients taking DRV/r had a higher incidence rate ratio of cardiovascular disease during a 5-year follow-up compared to pre-exposure, while no such increase was seen in patients taking ATV/r.

Older protease inhibitors had been shown to be associated with increased CVD risk, but the newer generation of drugs had not been similarly examined. A previous analysis of the D:A:D (Data collection on Adverse events of Anti-HIV Drugs) study had shown no effect of ATV/r with cardiovascular risk, but the follow-up time was short.

“This is the first time up to now that we have adequately long follow-up data to look at [ATV/r and DRV/r], and it has major impact because they are the most commonly used protease inhibitors,” said Lene Ryom, MD, PhD, a physician at the Center for Excellence of Health, Immunity, and Infections at Copenhagen University Hospital, who presented the research in an oral session at the 2017 Conference on Retroviruses & Opportunistic Infections in partnership with the International Antiviral Society.

The data suggest that ATV/r may be the best choice for patients at heightened risk of cardiovascular disease. “This is just the results from the first five years, and we need to reassess at some point, but according to what we know now, it does really look like a quite real effect,” Dr Ryom added.

The researchers examined longer-term results from 35,711 (47.8% white, 73.6% men, median age 44) participants in the D:A:D study, who were followed beginning January 1, 2009 through the earliest CVD diagnosis, last visit plus 6 months, or February 1, 2016.

After adjustment for baseline variables potentially on the causal pathway between PI use and cardiovascular disease, the researchers found that, compared to baseline pre-exposure levels, patients taking ATV/r had a 5-year incidence rate ratio (IRR) of CVD of 1.03 (95% confidence interval 0.90-1.18), while those taking DRV/r had an IRR 1.59 (95% CI, 1.33-1.91).

Time-updated adjustment analyses for factors potentially on the causal pathway made no meaningful difference in the calculation of incidence risk ratios. “This suggests that the association we say for boosted darunavir is not moderated by dyslipidemia, which is interesting and in contrast to what we saw in first-generation protease inhibitors,” Dr Ryom said during her talk.

Adjusting for bilirubin levels had no impact on the associations.

There was no data on drug dose, and due to the observational nature of the study, the researchers could not prove a causal association between CVD risk and use of either drug, but the results were convincing enough for Dr Ryom to consider a drug that appears friendlier to the cardiovascular system, particularly in high risk patients, though she also noted that there is evidence that ATV/r could lead to kidney stones and chronic kidney disease. “So it’s very difficult to balance the different risks. You really need to tailor your choice according to the patient that is in front of you,” Dr Ryom said.

The study was funded by The Oversight Committee for the Evaluation of Metabolic Complications of HAART, which included both academic and industry sources, and the Danish National Research Foundation. Dr Ryom reported having no financial disclosures.

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