Blood Lipid Profiles Improve after CD4-guided Treatment Interruption

Several studies in recent years have shown that interruption of antiretroviral therapy can be detrimental. The large SMART study, for example, found that HIV patients who deferred or interrupted treatment when their CD4 count was above 350 cells/mm3 had both a higher rate of classic AIDS-defining opportunistic illnesses and death, and an increased incidence of cardiovascular, liver, and kidney problems not traditionally considered HIV-related.

One of the reasons for structured treatment interruption was to spare patients some of the side effects associated with long-term antiretroviral therapy. However, the observed increase in cardiovascular and other problems that were previously assumed to be related to drug toxicity called this rationale into question.

As reported in the August 2008 Journal of Acquired Immune Deficiency Syndromes, Spanish researchers sought to determine whether metabolic and cytokine (chemical messenger) abnormalities would improve after interrupting treatment.

This prospective longitudinal multicenter study included 37 HIV positive patients on stable HAART regimens with a CD4 count above 600 cells/mm3 and HIV RNA above 50 copies/mL for at least 6 months. Participants were randomly assigned to either interrupt therapy or continue on HAART.

The investigators measured blood lipid (total cholesterol, triglycerides), apoprotein (Apo-A1, Apo-B, Apo-E), and adipocytokine (leptin, adiponectin, plasminogen activator inhibitor-1, monocyte chemotactic protein-1, interleukin-6, interleukin-8, and tumor necrosis factor-alpha) levels at baseline and 12 months after treatment interruption.

Results

• The 19 patients who underwent treatment interruption experienced a significant decrease in median cholesterol levels (P < 0.001).

• Median triglyceride levels, however, remained unchanged.

• There was a significant decrease in levels of Apo-A1 (P = 0.048) and Apo-B (P < 0.001).

• Given the greater decrease in Apo-B, the Apo-A1/Apo-B ratio increased after 12 months of treatment interruption, from 3.4 to 5.1 (P = 0.008).

• Levels of tumor necrosis factor-alpha increased (P = 0.034).

• There were no significant variations in leptin or adiponectin levels.

• The 18 patients who continued on HAART experienced no significant changes in any of the measured parameters.

Based on these findings, the investigators concluded, "The lipid profile and apoproteins levels change toward a less atherogenic profile after treatment interruption, arguing against a lipid-mediated mechanism to explain the increased cardiovascular risk in patients who interrupt treatment."

The causes of adverse cardiovascular outcomes in HIV positive individuals, both on and off treatment, are not yet fully understood. However, there is increasing evidence that inflammation related to HIV infection itself -- which may increase when viral replication rebounds during treatment interruption -- is likely to play a role.

Hospital General Universitario Gregorio Maranón, Madrid, Spain; Instituto de Salud Carlos III, Majadahonda, Spain; Hospital Universitario Ramón y Cajal, Madrid, Spain; Hospital Universitario 12 de Octubre, Madrid, Spain; Hospital Universitario La Paz, Madrid, Spain.

9/26/08

Reference
E Seoane, S Resino, D Micheloud, and others. Lipid and apoprotein profile in HIV-1-infected patients after CD4-guided treatment interruption. Journal of Acquired Immune Deficiency Syndromes 48(4): 455-459. August 2008.
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