Update on Inflammation and Cardiovascular Risk in People With HIV

BICOMBO Study Looks at the Safety of Abacavir

The BICOMBO study was a Spanish study that randomly assigned treatment-experienced participants to change the nuke portion of their regimen to one of the following:

• abacavir + 3TC -- 167 patients
• tenofovir + FTC -- 168 patients

The BICOMBO study team looked at a subgroup of participants from its study to assess the impact of nukes on the following:

• inflammation of the lining (endothelium) of blood vessels
• an imbalance between factors affecting blood flowing or clotting, favouring an excessive formation of blood clots
• insulin resistance (occurs in pre-diabetes and diabetes)

The BICOMBO researchers noted that factors such as cardiovascular disease, diabetes, uncontrolled HIV infection or other health conditions might affect the risk of developing a heart attack. Not taking these factors into account could have inadvertently led to biases when interpreting the results of several studies in which abacavir was linked to an increased risk for heart attack. So the BICOMBO team proposed to do a sub-study in a smaller group of patients, examining factors that can increase CVD risk, and therefore heart attacks, before and after its study.

Study Details

The BICOMBO sub-study focused on 46 participants who received abacavir + 3TC and 34 others who received tenofovir + FTC.

Some of the proteins they assessed in the blood included the following:

• high-sensitivity C-reactive protein (hsCRP)
• interleukins-6 and -10
• TNF-alpha
• adiponectin
• D-dimer
• insulin

Levels of these and other proteins were similar between participants at the start of the study.

The average profile of people at the start of the BICOMBO study was as follows:

• 20% female, 80% male
• age -- 43 years
• time spent on HAART -- four years
• use of protease inhibitors -- 8%

Changes After One Year

On the whole, people taking abacavir + 3TC did not have significant changes to levels of inflammatory proteins in their blood that were different from people taking tenofovir + FTC.

The researchers concluded that in otherwise-healthy participants the use of abacavir + 3TC compared to tenofovir + FTC did not result in significant differences in blood tests used to assess the following:

• inflammation
• endothelial dysfunction
• insulin resistance
• increased risk for the formation of blood clots

The BICOMBO team added that "these results argue against the involvement of abacavir in any of these mechanisms and therefore do not explain the higher risk of [heart attacks] associated with recent abacavir use in some cohort studies."

The strength of the BICOMBO study are as follows:

• participants were randomly assigned to receive treatment
• a wide range of blood tests to assess CVD risk factors was conducted

A weakness of BICOMBO is that it was a relatively small study. Another randomized study called STEAL, with a similar number of participants, found an unexpected increase in the risk of cardiovascular complications, including heart attacks, in treatment-experienced people who received abacavir + 3TC compared to others who received tenofovir + FTC. Some people in STEAL had pre-existing cardiovascular disease before taking that study's medication, particularly people who were assigned to receive abacavir.

• Note: As we went to press, further details about the STEAL study as well as new developments from DAD are about to become available and we will write reports on these developments in upcoming issues of Treatment Update.

References

1. Martinez E, Larousse M, Perez I, et al. No evidence for recent abacavir/lamivudine use in promoting inflammation, endothelial dysfunction, hypercoagulability, or insulin resistance in virologically suppressed HIV-infected patients: a sub-study of the BICOMBO randomized clinical trial (ISRCTN61891868). In: Program and abstracts of the 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention, July 19-22, 2009, Cape Town, South Africa. Abstract MOAB203.
2. Martin A, Bloch M, Amin J, et al. Simplification of antiretroviral therapy with tenofovir-emtricitabine or abacavir-lamivudine: a randomized, 96-week trial. Clinical Infectious Diseases. 2009 Nov 15;49(10):1591-601.