Boston, MA - Investigators from the large Data Collection on Adverse Events of Anti-HIV Drugs (DAD) study reported last week that HIV-positive patients taking antiretroviral therapy are at an increased risk of MI.[1] Although investigators stress the benefits of anti-HIV drugs, they say the cardiovascular risk profile of HIV-positive patients becomes elevated once they initiate therapy.

"This is a cohort study and not a randomized trial, so this is not the optimal methodology," Dr Jens Lundgren (Hvidovre University Hospital, Copenhagen, Denmark) told heartwire. "But the data show an increased signal of risk in HIV-positive patients treated with anti-HIV drug therapy. The association is biologically plausible given the fact that these drugs are able to alter various metabolic parameters known to be proatherogenic."

Concerns over increased cardiovascular events in HIV-infected people emerged with the increasing use of protease inhibitors (PIs) and nonnucleoside reverse-transcriptase inhibitors (NNRTIs). Lundgren said that over the past five years there has been a growing recognition that a relationship exists between increased exposure to combination therapy and the incidence of cardiovascular disease.

DAD is a large, international, multicohort study that includes information on 23 000 HIV-positive individuals from Europe, the US, and Australia. The primary objective of the study was to determine whether exposure to combination antiretroviral therapy is independently associated with the risk of MI. Presenting updated findings from the DAD study group at the 2005 Conference of Retrovirus and Opportunistic Infections last week, Lundgren reported that since 1999, there were 277 reported MIs, 28% of which were fatal. The average patient age was 39 years.

Lundgren told heartwire that antiretroviral drugs are known to increase total and LDL cholesterol levels, but "that really doesn't explain the whole story." He said the drugs may alter insulin resistance and noted that many treated with anti-HIV drugs develop a pattern similar to syndrome X. He stressed, however, that while treatment with the potent antiretroviral drugs appears to increase the risk of fatal and nonfatal MIs, the adverse effects are still outweighed by the benefit of treatment.

"What we're discussing here are side effects, but we should never lose perspective of the benefits of these drugs," said Lundgren. "In my cohort of patients, for example, back in 1995, if we followed 100 patients for one year, we would expect 23% of them to die. Now, that percentage is down to 1.5%. There has been a dramatic improvement in prognosis and any negative effects that come from therapy should be seen in this context."

Lundgren noted that the reduction in mortality in those infected with HIV following the widespread use of combination antiretroviral therapy has seen infected individuals now experiencing clinical events typical of an aging population. With regard to the association of anti-HIV drug therapy and the risk of MI, he said patients should try to "modify the modifiable risk factors and counteract the effect from treatment."

He added that research will next be focused on teasing out whether exposure to anti-HIV drugs and the risk of cardiovascular disease is equal among the various antiretroviral drug classes. "This is not something that we can answer today, but something we hope to be able to answer in a year or two," he said.