London - Researchers say a commonly used AIDS drug appears to nearly double the risk of a heart attack.

In a study published online by the medical journal Lancet, the researchers also say another less frequently used AIDS drug increases the chances of a heart attack by 50 per cent.

Experts say doctors should be aware of the increased risks.

But they do not recommend that patients abandon the two drugs, Ziagen and Videx.

AIDS drugs "are wonderful and lifesaving, but they do have toxicity problems,'' says Dr. Charlie Gilks, an AIDS treatment expert at the World Health Organization.

"It may be that we can continue to use them, but we need to be aware of their long-term problems,'' he said.

AIDS drugs are used in combinations, so they could be swapped with others if necessary.

Experts have suspected that AIDS drugs could cause heart problems, but no definitive evidence has been available. The drugs come with many side effects, including liver and kidney failure, chronic fatigue syndrome, hepatitis and jaundice.

Jens D. Lundgren of the University of Copenhagen and colleagues analyzed data from more than 33,000 people infected with the AIDS virus in Europe, the United States and Australia to study the long-term effects of five AIDS drugs. The patients were followed for up to five years to see who had heart problems.

In the 754 patients who had heart attacks, 192 had recently taken Ziagen, also known as abacavir, and 124 had recently taken Videx, also known as didanosine.

Those who took Ziagen, included in many AIDS regimens worldwide, had twice the chances of a heart attack compared to patients on other AIDS drugs, the researchers reported. Those on Videx had a 50 per cent higher chance. But the risk disappeared six months after patients stopped taking the drugs.

Lundgren said patients already susceptible to heart problems were most at risk.

For men over 40 who smoked and were overweight, the risk of a heart attack were as high as 20 per cent. Taking Ziagen increased that risk to nearly 40 per cent.

For those without known heart risks, the chances of a heart attack were low -- between one to five per cent. Once they were on the drug, their risk ranged from two to nearly seven per cent.

No increased heart attack risk was found for patients on the other drugs in the study, zidovudine (AZT), stavudine (Zerit) or lamivudine (Epivir). The medications all block an enzyme that the AIDS virus needs to multiply.

GlaxoSmithKline PLC, which makes Ziagen, said their own analysis of their database of about 14,600 HIV patients, did not support the Lancet study's conclusions.

"We were unable to show any increased risk in heart attacks,'' said Gwenan White, a company spokeswoman.

The findings could influence how AIDS patients are treated globally, as health authorities like WHO reconsider their treatment guidelines. Ziagen and Videx are currently recommended by WHO for people with HIV worldwide.

"In developed countries, doctors have 24 different antiretrovirals to choose from if one isn't appropriate. But if that happens in resource-poor countries, it is not so simple,'' said Gilks, who was not connected to the study.

As AIDS patients continue to live longer, experts said they would probably see more of the rarer side effects emerge.

"No drug is risk-free,'' Lundgren said. "For all patients, it's a matter of finding the right balance.''

The research was funded by the European Medicines Agency, a regulatory group, which solicited contributions from makers of AIDS drugs for studies on their long-term effects.

Abstract

Background

Whether nucleoside reverse transcriptase inhibitors increase the risk of myocardial infarction in HIV-infected individuals is unclear. Our aim was to explore whether exposure to such drugs was associated with an excess risk of myocardial infarction in a large, prospective observational cohort of HIV-infected patients.

Methods

We used Poisson regression models to quantify the relation between cumulative, recent (currently or within the preceding 6 months), and past use of zidovudine, didanosine, stavudine, lamivudine, and abacavir and development of myocardial infarction in 33 347 patients enrolled in the D:A:D study. We adjusted for cardiovascular risk factors that are unlikely to be affected by antiretroviral therapy, cohort, calendar year, and use of other antiretrovirals.

Findings

Over 157 912 person-years, 517 patients had a myocardial infarction. We found no associations between the rate of myocardial infarction and cumulative or recent use of zidovudine, stavudine, or lamivudine. By contrast, recent--but not cumulative--use of abacavir or didanosine was associated with an increased rate of myocardial infarction (compared with those with no recent use of the drugs, relative rate 1�90, 95% CI 1�47-2�45 [p=0�0001] with abacavir and 1�49, 1�14-1�95 [p=0�003] with didanosine); rates were not significantly increased in those who stopped these drugs more than 6 months previously compared with those who had never received these drugs. After adjustment for predicted 10-year risk of coronary heart disease, recent use of both didanosine and abacavir remained associated with increased rates of myocardial infarction (1�49, 1�14-1�95 [p=0�004] with didanosine; 1�89, 1�47-2�45 [p=0�0001] with abacavir).

Interpretation

There exists an increased risk of myocardial infarction in patients exposed to abacavir and didanosine within the preceding 6 months. The excess risk does not seem to be explained by underlying established cardiovascular risk factors and was not present beyond 6 months after drug cessation.