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Treating HIV Infection with Intermittent Antiretrovirals Fails

A strategy designed to minimize drug toxicity backfires, leading to higher morbidity and mortality.

When the long-term toxicities of HIV drugs first became apparent, some experts suggested that these drugs might best be administered like chemotherapy: given in short courses when disease activity is high, stopped to allow patients to recover, then resumed when disease returns. This technique was evaluated in a large international study.

More than 5000 HIV-infected participants were randomized to receive antiretrovirals either as they are usually given (a daily combination of 3 or more drugs designed to keep the plasma viral load as low as possible) or as intermittent treatment (drug combinations given daily until CD4 counts exceeded 350 cells/mm³, then stopped, and resumed when counts fell below 250 cells/mm³). Drugs could also be started (or restarted) for clinical AIDS-related problems at any CD4-cell count. The choice of specific drugs was left to the subjects' primary caretakers.

After a mean 16-month follow-up, rates of all-cause mortality and AIDS-related opportunistic disease were significantly higher with intermittent therapy than with continuous treatment. The combined rate of cardiovascular, hepatic, and renal disease was also higher with intermittent therapy. The study was stopped prematurely because of these results.

Comment: These findings indicate that maintaining continuous control of HIV infection results in considerably better clinical outcomes than does intermittent treatment. Even the clinical endpoints associated with drug toxicity (heart, liver, and kidney problems) were more common in the intermittently treated group. The bottom line: The dangers of untreated HIV infection appear to far outweigh the toxicity of antiretrovirals, even for patients whose CD4 counts are kept at "safe" levels of >200 cells/mm³.

— Abigail Zuger, MD

Published in Journal Watch General Medicine November 29, 2006

Citation(s):

The Strategies for Management of Antiretroviral Therapy (SMART) Study Group. CD4+ count–guided interruption of antiretroviral treatment. N Engl J Med 2006 Nov 30; 355:2283-96.

• Original article (Subscription may be required)
• Medline abstract (Free)

Currier JS and Baden LR. Getting smarter — The toxicity of undertreated HIV infection. N Engl J Med 2006 Nov 30; 355:2359-61.

• Original article (Subscription may be required)
• Medline abstract (Free)