番茄社区

GLASGOW -- An immediate switch to dolutegravir-based therapy from ritonavir-boosted protease inhibitors in virologically suppressed HIV-infected patients with high cardiovascular risk factors was associated with a mixed bag of changes in certain biomarkers at 48 weeks, a researcher said here.

Compared with patients in the ritonavir-boosted protease inhibitor group, those in the dolutegravir group had significant decreases in soluble CD14 (sCD14), a non-specific marker of monocyte activation, and adiponectin, a protein involved in regulating glucose levels, reported Esteban Martinez, MD, of the University of Barcelona in Spain.

But the authors found that percent change in sCD14 was inversely correlated with percent change in CD4 count, and percent change in adiponectin was inversely correlated with percent change in BMI -- potentially producing decreasing and increasing cardiovascular effects in these patients, respectively.

At a presentation at the International Conference on Drug Therapy in HIV Infection (), he said this was a planned substudy of the 96-week , a randomized trial of virologically suppressed adults either immediately switched to dolutegravir-based therapy or with a "deferred" switch from ritonavir-boosted protease inhibitors. The primary study, Martinez said, showed that dolutegravir-based therapy was linked with an almost 8% reduction in low-density lipoprotein (LDL) cholesterol and "may have had an impact on major cardiovascular events."

Here, researchers wanted to see if, besides lipid changes, there were other interrelated mechanisms that might have been impacted by the switch in therapies, such as markers associated with:

• Inflammation
• Endothelial dysfunction
• Monocyte immune activation
• Oxidation
• Insulin resistance
• Hypercoagulability
• Myocardial injury
• Heart failure
• Kidney glomerular injury
• Kidney tubular injury

The original NEAT022 study was conducted in six European countries in 32 centers. Participants were HIV-infected individuals with a viral load of <50 copies/mL, who were on triple-therapy protease inhibitor/ritonavir plus two nucleoside reverse transcriptase inhibitors; all were age ≥50 and/or had a Framingham Risk Score of ≥10% at 10 years.

In this substudy, 313 of these participants (147 on dolutegravir-based therapy and 166 on ritonavir-boosted protease inhibitors) had data available at 48 weeks. Almost 90% of patients were age ≥50 and three-quarters had a Framingham Risk Score of >10%. Most were men of white race, and participants had a "relatively low duration" of undetectable viral load (<5 years). Martinez added that 40% were smokers, about 40% had high blood pressure, and 7% had diabetes.

Overall, patients in the dolutegravir group had significant decreases in both sCD14 and adiponectin (-11% each, P<0.001 for both) compared with those in the ritonavir-boosted protease inhibitor group from baseline to week 48. There was also a trend towards significance associated with decreases in high-sensitivity C-reactive protein, which has been linked with the presence of heart disease ( -13%, P=0.069), as well as oxidized LDL (-13%, P=0.084).

Martinez noted that the overall cardiovascular impact of the NEAT022 study was positive, but there was a decrease in adiponectin associated with BMI gain, concluding that "this substudy highlights the importance of further assessing the potential impact of [dolutegravir] therapy on the mechanisms involved in body weight."

Other planned substudies from the NEAT022 study include examining changes at 48 weeks on carotid intima-media thickness, arterial stiffness, an ECG analysis, and special lipid fractions.