FDA Report Suggests Abacavir May Not Increase Myocardial Infarction Risk After All

In a poster that was presented on March 2 at the 18th Conference on Retroviruses and Opportunistic Infections (CROI 2011), the U.S. Food and Drug Administration (FDA) reported that it has found no evidence of an association between abacavir (ABC, Ziagen) treatment and an increased risk of myocardial infarction (heart attack) in a meta-analysis of 26 randomized trials of the drug. The meta-analysis included a total of 5,028 patients on abacavir and 4,804 non-abacavir patients, with a mean follow-up per person of 1.62 years. The studies recorded 47 total cases of myocardial infarction; they occurred in 18 of the 26 studies.

Several prior studies have found contradictory evidence about abacavir and increased cardiovascular risk. Worrisome data from the D:A:D and SMART studies in particular compelled the U.S. Department of Health and Human Services (DHHS) HIV treatment guidelines panel in 2008 to drop abacavir (taken in the form of abacavir/lamivudine, or Epzicom [known as Kivexa in Europe]) from its list of recommended first-line nucleosides for the treatment of treatment-naive, HIV-infected patients. Whether this new FDA report will reverse this decision remains to be seen.

GlaxoSmithKline recently reported that it is developing a once-a-day pill (called 572-Trii) containing its experimental integrase inhibitor S/GSK1349572 (which now has a generic name, dolutegravir), abacavir and lamivudine (3TC, Epivir) for treatment-naive patients. This new FDA review may open the door for Glaxo to request that the DHHS HIV treatment guidelines panel include abacavir and 572-Trii as recommended first-line therapy options once the 572-Trii studies are finished. (In early studies, dolutegravir has shown a promising ability to reduce HIV viral load in patients with resistance to the only currently approved integrase inhibitor, raltegravir [RAL, Isentress]. Head-to-head studies between dolutegravir and raltegravir are currently starting.)