Lipids improved by switching from ritonavir to cobicistat as a booster for darunavir


Switching from ritonavir to cobicistat is associated with significant improvements in cholesterol and triglyceride levels for people with dyslipidaemia, investigators from Spain report in HIV Medicine. Ritonavir was replaced with cobicistat to boost the protease inhibitor darunavir. Six months after the switch, cholesterol and triglycerides had significantly improved among people with lipid abnormalities at baseline.

“More than 50% of the total study population presented with dyslipidaemia at baseline,” comment the researchers. “A significant improvement in all lipid parameters, including HDL cholesterol, was seen 24 weeks after the switch in those subjects with hypercholesterolaemia at baseline, and triglyceride levels improved mainly in those who presented with hypertriglyceridaemia at baseline, while virological efficacy and immunological status were maintained after the replacement,” write the researchers. “These results indicate that replacement of ritonavir with cobicistat could decrease the percentage of subjects with dyslipidaemia associated with ART [antiretroviral therapy] and consequently cardiovascular risk.”

Cobicistat is an approved boosting agent for certain antiretroviral drugs, including the protease inhibitor darunavir (a co-formulation of the two drugs is now available under the brand names Rezolsta or Prezcobix). Clinical trials showed that cobicistat/darunavir is as safe and effective as ritonavir-boosted darunavir. Ritonavir has been associated with significant drug interactions and side-effects, including lipid abnormalities. Protease inhibitors boosted by ritonavir are a risk factor for the development of cardiovascular disease, which is a major cause of illness and death in people with HIV. The effect on lipids of switching from ritonavir to cobicistat has received little attention.

This study

Investigators in Spain designed a retrospective, observational study examining changes in lipids after replacement of ritonavir with cobicistat as the boosting agent for darunavir. The study population consisted of 299 people who made this treatment change between December 2015 and May 2016. Fasting lipids were checked just before the treatment switch, and again six months later.



Fat or fat-like substances found in the blood and body tissues. Lipids serve as building blocks for cells and as a source of energy for the body. Cholesterol and triglycerides are types of lipids.


A waxy substance, mostly made by the body and used to produce steroid hormones. High levels can be associated with atherosclerosis. There are two main types of cholesterol: low-density lipoprotein (LDL) or ‘bad’ cholesterol (which may put people at risk for heart disease and other serious conditions), and high-density lipoprotein (HDL) or ‘good’ cholesterol (which helps get rid of LDL).

boosting agent

Booster drugs are used to ‘boost’ the effects of protease inhibitors and some other antiretrovirals. Adding a small dose of a booster drug to an antiretroviral makes the liver break down the primary drug more slowly, which means that it stays in the body for longer times or at higher levels. Without the boosting agent, the prescribed dose of the primary drug would be ineffective.


The basic 'building blocks' from which fats are formed.


observational study

A study design in which patients receive routine clinical care and researchers record the outcome. Observational studies can provide useful information but are considered less reliable than experimental studies such as randomised controlled trials. Some examples of observational studies are cohort studies and case-control studies.

Hypercholesterolaemia was defined as total cholesterol above 200mg/dl and/or LDL ('bad') cholesterol above 130mg/dl, with hypertriglyceridaemia defined as triglyceride levels above 200mg/dl.

Overall, the median age was 49 years and 85% of the study participants were men. Just under half were taking darunavir/ritonavir monotherapy, with 9% receiving darunavir/ritonavir bitherapy and 41.5% triple-drug ART. All the study participants had an undetectable viral load and median CD4 cell count was 643 cells/mm3. The majority of individuals (52%) had abnormal lipids.

Viral control and CD4 count were unaffected by the treatment change.

Analysis of the entire study population showed that replacing ritonavir with cobicistat had no significant effect on cholesterol, though a significant decline was observed in median triglyceride levels (p = 0.018).

Restricting analysis to people with lipid abnormalities at baseline, showed significant falls in total cholesterol (p < 0.001), LDL cholesterol (p = 0.047), increases in HDL or good cholesterol (p = 0.002), and a decline in trigylcerides (p < 0.001).

The observational design of the study meant that the authors were not able to exclude other possible causes for these lipid changes, such as diet and exercise. And the percentage of people on boosted-darunavir monotherapy is much higher than it would be in some other countries. Further prospective randomised studies are therefore needed. Nevertheless, the investigators were encouraged by their findings.

“This exploratory analysis provides, for the first time, descriptive results demonstrating the beneficial impact on the lipid profile that cobicistat seems to have when it is used as a booster/pharmaco-enhancer of darunavir in HIV-1 infected subjects,” conclude the authors. “In addition, this new co-formulation makes the compound easier to take, thus improving adherence.”


Echeverría P et al. Significant improvement in triglyceride levels after switching from ritonavir to cobicistat in suppressed HIV-1-infected subjects with dyslipidaemia. HIV Med. Online edition. DOI: 10.1111/hiv.12530 (2017).