The Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study has been following 11 HIV populations in Europe, North America, and Australia since 1999. Last year study researchers reported that there was about a 10% increase risk of heart attacks with protease inhibitors compared to nonnucleoside reverse transcriptase inhibitors.
At this year's Conference on Retroviruses and Opportunistic Infections the researchers presented a poster comparing the cardiovascular risk of specific nucleoside drugs.
This study identified 517 heart attacks in 33,000 patients over five years. Somewhat unexpectedly there was no increased risk of heart attack with AZT or Zerit despite the drugs' association with lipoatrophy, elevated lipids, and insulin resistance.
More surprisingly, the researchers found that the relative risk of heart attack increased by 90% with Ziagen and 49% with Videx. Even more confusing was the fact that this elevated risk happened within the first six months of starting the drugs but did not increase with longer use. Once the drugs were stopped, the increased risks disappeared.
Adjusting for other risk factors such as smoking, elevated lipids, and hypertension produced the same results.
Because there appears to be no plausible mechanism to explain these results, the investigators made the unusual move to issue a position statement while the full report is being finalized. (Posters are brief 200 - 300 word summaries.) They reminded us that this is an observational report, which cannot prove causality. Only a prospective randomized trial can do that. Next they emphasized that this is a relative, not absolute, risk increase. This means that for someone with a 1% risk (such as a 20-year-old, non-smoking man) the risk increases to only 1.9%. However, in someone with a 20% risk (a 50-year-old man who smokes and has high blood pressure) the risk increase could be substantial
These explanations were meant to avoid over-interpretation of the poster data and a knee-jerk reaction to take everyone off Ziagen, which would include stopping treatment with the combination pill Epzicom that contains both Ziagen and Epivir. Some experts question whether a 'channeling bias' occurred in the study, meaning that patients were selected to receive Ziagen based on other subtle criteria we haven't accounted for.
And many worry that patients will stop their anti-HIV medications on their own. This concern stems in part from the results of the Strategies for Management of Antiretroviral Therapy (SMART) study that looked at treatment interruptions. That study showed those who interrupted their HIV treatment had an increased risk of heart attack due to a significant rise in inflammatory markers for plaque and clot formation that occurs during treatment breaks.
The final caveat was that Viread was not part of the D:A:D study because it had not been on the market long enough when the study began to accrue a significant number of patients taking the medication.
The bottom line is that HIVers should talk with their physicians about whether to stay on Ziagen and not unilaterally stop this medication. Equally important is engaging in this conversation presents an ideal time to focus on controlling the much greater heart attack risk factors of smoking, high blood pressure, elevated lipids, and diabetes.
Bowers is an HIV specialist and board-certified physician in family practice, and he is a senior partner with Pacific Oaks Medical Group, one of the largest U.S. practices devoted to HIV care, in Beverly Hills, Calif.
