Interrupting Antiretroviral Therapy Does Not Lower the Risk of Cardiovascular Disease in People with HIV

By Liz Highleyman

Due to concerns about metabolic complications associated with the use of antiretroviral therapy -- especially elevated blood fat levels due to protease inhibitors -- researchers have explored various alternative therapy approaches including drug class-sparing regimens and structured treatment interruptions.

In a study presented at the recent 47th Interscience Conference on Antimicrobial Agents and Chemotherapy in Chicago, researchers evaluating changes in fasting lipid levels, immune activation, and cardiovascular risk among participants who interrupted treatment in the ACTG 5102 trial.

The study enrolled 47 patients on stable antiretroviral therapy with suppressed viral load (below 200 copies/mL) and high CD4 cell counts (at least 500 cells/mm³). Participants were randomly assigned to continue their current antiretroviral regimen for 18 weeks, with or without 3 cycles of interleukin 2 (IL-2), a cytokine that stimulates T-cell proliferation. After 18 weeks, all patients stopped taking antiretroviral drugs until their CD4 count dropped below 350 cells/mm³.

This threshold is the same as that used in the Staccato trial, which reported promising results including reduced cholesterol levels and decreased lipodystrophy in the treatment interruption arm. In the ill-fated SMART trial, CD4 cell counts were allowed to fall to 250 cells/mm³ before patients resumed treatment. In  that study, those who interrupted treatment had a higher risk of both opportunistic illnesses and presumably “non-AIDS-related” cardiovascular, kidney, and liver complications.

In the ACTG 5102 trial, patients’ blood lipid and glucose levels were measured every 8 weeks initially, then every 2 to 8 weeks after treatment interruption. Immune activation was evaluated by flow cytometry and soluble TNFR2 levels.

Results

·         By week 8 after treatment interruption, total cholesterol (TC) decreased by a median of 32 mg/dL.

·         Triglycerides levels fell by a mean 35 mg/dL.

·         Levels of both LDL (“bad”) and HDL (“good”) cholesterol also decreased (by 14 mg/dL and 2 mg/dL, respectively).

·         TC-to-HDL ratio remained unchanged.

·         No changes were observed in glucose or insulin levels.

·         After treatment interruption, there was marked increase in immune activation, coinciding with viral load rebound.

Conclusion

Based on these findings, the investigators concluded that, “Interrupting antiretroviral therapy does not reduce cardiovascular disease risk, as the improvements in lipid parameters are modest and overshadowed by the decreased HDL levels, the increased immune cell activation, and systemic inflammatory responses associated with HIV viremia.”

The added that, “These effects could put the patients at a greater cardiovascular disease risk than when they were receiving antiretroviral treatment.”

09/28/07

Reference
P Tebas, K Henry, R Matinning, and others. Antiretroviral Treatment Interruption, Immune Activation and Cardiovascular Risk. 47th Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago, IL. September 17-20, 2007. Abstract H-378.