icon-folder.gif   Conference Reports for NATAP  
  Glasgow HIV
28 - 31 October 2018
Glasgow, UK
Back grey_arrow_rt.gif
SVR With DAAs--and Darunavir--Tied to Lipid Jumps in Big HCV/HIV Group
  HIV Drug Therapy, Glasgow 2018, October 28-31, 2018, Glasgow
Mark Mascolini
Total and low-density lipoprotein (LDL) cholesterol rose significantly in HCV/HIV-coinfected people who attained sustained virologic response (SVR) with a direct-acting antiviral (DAA) regimen [1]. This 468-person study also found significant gains in total cholesterol among people taking darunavir/ritonavir.
Researchers working with Italy's Icona HIV cohort noted that previous work links HCV to lower cholesterol levels. As a result, elimination of HCV with curative DAA therapy leads to "a sharp and significant increase" in total and LDL cholesterol that persists after DAA therapy stops. Study of the D:A:D group, a multicohort HIV population, found that longer use of ritonavir-boosted darunavir but not atazanavir is associated with cardiovascular events independently of lipid concentrations [2].
To pursue these lines of evidence, Icona investigators analyzed lipids and other biomarkers in HCV/HIV-coinfected antiretroviral-treated people before and after they started a curative DAA regimen for HCV. The first pair of measures were the two most recent values in the 12 months before DAAs began. The second pair of measures were the latest collected 4 to 12 months after the end of treatment with DAAs. The researchers calculated marker changes within each pair and from before to after DAA therapy. They used ANCOVA analysis to determine whether darunavir/ritonavir, atazanavir/ritonavir, or raltegravir affected these changes.
The 468 antiretroviral-treated people who achieved SVR had a median age of 52, median body mass index of 24 kg/m2, and median CD4 count of 584. Women made up 26% of the group. While 24% took a raltegravir-based antiretroviral regimen, 22% took darunavir/ritonavir and 20% took atazanavir/ritonavir.
The paired marker analysis indicated that total cholesterol, LDL cholesterol, and platelets tended to be stable or falling before DAA therapy began. But total and LDL cholesterol, as well as platelets, climbed significantly from before DAA therapy until after it stopped. Total cholesterol rose by an average 21.6 mg/dL (from 158.7 to 180.3, P < 0.01), LDL cholesterol rose by an average 20.7 mg/dL (from 88.7 to 109.4, P < 0.01), and platelets rose an average 13.6 thousand/mcL (from 153.0 to 166.6, P < 0.01). "Good" high-density lipoprotein did not change significantly before or after DAA therapy.
Compared with people not taking darunavir/ritonavir, those taking the boosted protease inhibitor gained an average 10.5 mg/dL in total cholesterol after DAA therapy stopped (P = 0.02). In contrast, total cholesterol fell in that period among people taking raltegravir (-8.5 mg/dL, P = 0.04). Total cholesterol did not change in people taking atazanavir/ritonavir.
The researchers proposed that "a complex and rapid change in risk factors for cardiovascular disease" occurs in HCV/HIV-coinfected people after HCV elimination with DAA therapy. They noted that the clinical impact of these short-term lipid changes on long-term cardiovascular risk remains unknown. But they pointed out that lipid and platelet changes occurred over a short period and "potentially contribute to an increase in cardiovascular risk through shared or separate pathways." The Icona team stressed the importance of assessing a person's cardiovascular risk profile before starting DAA therapy.
1. Taliani G, Marchetti G, Cingolani A, et al. Increased total and LDL cholesterol plasma levels upon direct antiviral agents (DAAs) driven HCV eradication. HIV Drug Therapy, Glasgow 2018, October 28-31, 2018, Glasgow. Abstract P245.
2. 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:e291-300.