Raltegravir kinder to bones and body fat than boosted protease inhibitors in Spanish trial

Raltegravir (Isentress)-based treatment appears to have a more favourable impact on fat accumulation and bone metabolism compared to therapy based on a ritonavir-boosted protease inhibitor, according to Spanish research published in the online edition of AIDS.

The study involved 74 patients who were taking HIV therapy including a ritonavir-boosted protease inhibitor. Approximately half were randomised to switch to the integrase inhibitor raltegravir. Changes in body fat composition and bone mineral density were assessed one year after randomisation and generally favoured raltegravir.

“In our study, raltegravir showed a more neutral effect on body fat,” write the investigators. “To our knowledge our study provides the first published data about the effects of raltegravir on bone composition. Patients switching…to raltegravir showed improvements in virtually all locations.”

Effective antiretroviral therapy means that many HIV-positive patients have a near normal life expectancy.

However, HIV treatment can cause long-term side-effects, and it is arguable that one of the most feared is the syndrome of body fat changes known as lipodystrophy.

There are two components to lipodystrophy. The first is fat loss, or lipoatrophy. This is associated with older drugs in the nucleoside reverse transcriptase inhibitor (NRTI) class. The second component involves the accumulation of visceral fat, or lipohypertrophy, especially around the trunk. This side-effect may be caused by protease inhibitors. However, little is known about the impact of raltegravir on body composition.

In addition, there are concerns that antiretroviral therapy may have an impact on bone metabolism. Studies have yielded conflicting results concerning protease inhibitor therapy and bone loss, and the effect of raltegravir on bone metabolism has received little attention.

Therefore, between June and December 2008 investigators from the SPIRAL clinical trial in Barcelona designed a sub-study involving 74 patients who were taking long-term virologically suppressive HIV therapy based on a ritonavir-boosted protease inhibitor (median of 32 months).

The patients were randomised on an equal basis to either to continue their current therapy or to switch from a protease inhibitor to raltegravir.

Both DEXA and CT scans were performed at baseline. These were repeated 48 weeks later in order to assess the impact of the alternative regimens on body composition and bone density.

A significant increase in visceral adipose tissue (p = 0.002) and total adipose tissue (p = 0.01) was seen in the patients who remained on a ritonavir-boosted protease inhibitor.

The investigators found these outcomes “striking”, and comment: “Despite long-term protease inhibitor use, patients continuing the same protease inhibitor/ritonavir had a significant increase in visceral adipose tissue and total adipose tissue after 48 weeks, suggesting that fat changes probably continue over time with protease inhibitors/ritonavir.” They believe these data show “a class effect of protease inhibitors on increasing abdominal fat.”

In contrast, no significant changes were seen in the visceral fat levels of patients treated with raltegravir.

The scans also revealed the different impact of the two regimens on bone mineral density.

There were no significant changes in the bone mineral density of the patients who continued to take therapy based on a ritonavir-boosted protease inhibitor.

However, total bone mineral density increased significantly (p = 0.02), as did total hip bone mineral density (p = 0.01).

“Switching from a protease inhibitor/ritonavir to raltegravir showed improvements in bone mineral density…while maintaining the protease inhibitor/ritonavir showed an increase in visceral adipose tissue and total adipose tissue,” conclude the authors.

They believe their findings could have implications for HIV treatment strategies: “Raltegravir might be considered a safe treatment option in certain patients, especially in the HIV-infected aging population, because of its already known lipid effects and now because of its potential beneficial bone effects.”

Curran A et al. Body composition changes after switching from protease inhibitors to raltegravir: SPIRAL-LIP substudy. AIDS 25, online edition, doi: 10.1097/QAD.0b013e32834f3507, 2011 (click here for the free abstract).