Ritonavir concentrations not correlated with lipid levels in people with HIV taking boosted atazanavir or boosted darunavir

Michael Carter
Published: 06 April 2015

People taking HIV treatment based on ritonavir-boosted atazanavir and darunavir have comparable long-term increases in lipid levels, investigators from the United States report in the online edition of Clinical Infectious Diseases. Trough concentrations of ritonavir were not associated with lipid levels. This is an important finding.

The authors explain: “The lipid changes experienced with ritonavir boosted PI [protease inhibitor] therapy are speculated to be driven to a larger extent by the ritonavir component of the regimens”. This could be because of the way ritonavir is processed by the body. The present research provided an opportunity to test this theory, but showed “associations between ritonavir exposure and lipid changes over 48 and 96 [weeks] were…not apparent (both overall and within specific PI regimens).”

Thanks to antiretroviral therapy, many people with HIV now have a normal life expectancy. However, several anti-HIV drugs, especially protease inhibitors, have been associated with lipid disturbances. Given that cardiovascular disease is an increasingly important cause of illness and death in people with HIV, it’s important to identify which drugs carry the biggest risk of lipid abnormalities.

ACTG 5257 was an open-label, phase III, randomised study comparing the safety and efficacy of regimens based on ritonavir-boosted atazanavir, ritonavir-boosted darunavir or the integrase inhibitor raltegravir. All the participants in the study were antiretroviral naive at baseline (had not previously taken treatment when the study started) and were also taking the fixed-dose combination emtricitabine/tenofovir (Truvada).

The study also gave investigators the opportunity to compare long-term changes in lipid profiles, incidence of metabolic syndrome and alterations in body shape according to regimen. Additionally, for people taking the protease inhibitors, the investigators also examined whether trough levels of ritonavir were correlated with lipid changes and if these differed between regimens.

Approximately 1800 people were recruited to the study between 2009 and 2011. A quarter were women, 34% were African American, 42% were white and 21% Hispanic.

A fifth of participants had metabolic syndrome at baseline. Prevalence did not differ by regimen and lipid profiles were also comparable between regimens.

During 96 weeks of follow-up, lipid levels increased with all three regimens. However, these were milder with raltegravir compared to the boosted protease inhibitors (p < 0.001).

Approximately a fifth of participants in each study arm developed metabolic syndrome during follow-up. At week 96, rates of use of lipid-lowering agents were also comparable between the three study medications (9 to 14%). People taking raltegravir experienced a larger increase in waist circumference compared to those treated with ritonavir-darunavir but not ritonavir-atazanavir.

Trough concentrations of ritonavir did not differ between arms, and there was no evidence of a correlation between ritonavir levels and lipid profile.

“Raltegravir produced the most favourable lipid profile compared with the two ritonavir boosted PIs,” comment the authors.

They were concerned by the high prevalence of metabolic syndrome at baseline and also the approximately 20% incidence observed during follow-up.

“The long-term clinical significance of the lipid changes noted with the two ritonavir boosted PI regimens relative to the raltegravir based regimen deserve further evaluation, particularly when initiating antiretroviral therapy in patients with high cardiovascular risk profiles,” conclude the authors.


Ofotokun I et al. Comparison of the metabolic effects of ritonavir-boosted darunavir or atazanavir versus raltegravir, and the impact of ritonavir plasma exposure: ACTG 5257. Clin Infect Dis, online edition, 2015.

Community Consensus Statement on Access to HIV Treatment and its Use for Prevention

Together, we can make it happen

We can end HIV soon if people have equal access to HIV drugs as treatment and as PrEP, and have free choice over whether to take them.

Launched today, the Community Consensus Statement is a basic set of principles aimed at making sure that happens.

The Community Consensus Statement is a joint initiative of AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC and NAM/aidsmap

This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends checking whether this is the most current information when making decisions that may affect your health.

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member of your healthcare team for advice tailored to your situation.