What Is Risk For Increased Heart Disease From HAART?
      Reported by Jules Levin & Gilbert Kaufman, MD, Univ Hosp Basel, Switzerland

Studies have shown that patients taking HAART can see lab anormalities in tests that when increased in HIV- individuals are risk factors for heart disease. We have seen anecdotal reports of patients on HAART experiencing premature heart problems. So, what is the real risk? Even though we have not yet seen large scale increases in heart problems for patients on HAART, a number of researchers have concluded that its reasonable to assume there is increased risk. For people with additional risk factors such as smokers, genetic & family predisposition for heart disease & diabetes, risk may be increased.

However, one must consider & weigh the short & long term risks. For example, having elevated cholesterol, sugar & triglycerides in a person on HAART with no other risk factors may lead to a heart problem in 10 years. A person's current age is an important consideration. If you are 50 risk for heart disease increases compared to a person aged 35. The French study below shows myocardial infarction (MI) was disagnosed in 54 of 19,000 men exposed to PI regimens. This study found that patients on PI therapy for 18 months had higher rates of MI than the general public, and after PI therapy for 30 months rates for MI increased further. But the numbers of people experiencing the MI were small, 18 persons on PI for 1-29 months and 13 persons on PI therapy for more than 30 months.

It's possible that within a few years additional HIV therapies will be available, such as entry inhibitors, that may need lead to lipid abnormalities. It's possible that medical treatment interventions may emerge from research that will alleviate risk for heart disease as they reduce lipid abnormalities. So, certainly we should be concerned about potential heart problems but it also needs to be considered in perspective.

There are things you can do to potentially improve your situation: stop smoking, improve diet, exercise (even just walking for 20 minutes several times per week). A number of studies have shown that switching HIV therapy to PI sparing regimens have improved some lab abnormalities. Nevirapine and abacvir based regimens appear to improve lipid abnormalities the most consistently in studies. In switch studies to efavirenz these improvements have not been seen as often or consistently. At ICAAC in September there was more detailed discussion of these questions & studies. Here are links to ICAAC Reports and Reports from the September Lipodystrophy Conference:

ICAAC Switching Studies
http://www.natap.org/2000/sept/ICAAC/ICAAC_rpt14_switching_studies_110600.htm

Lipodystrophy Conference
http://www.natap.org/2000/sept/lipo_workshop/selected_reports_from_the_lipody_81500.htm

ICAAC Reports
http://www.natap.org/2000/sept/ICAAC/selected_reports_from_ICAAC_81900.htm

The NATAP web site has an interesting article in Lipid Evaluation & Management of Elevated Lipids in HIV written by Carl Fichtenbaum, MD from the Univ of Cincinnati and a researcher with the ACTG:
http://www.natap.org/2000/sept/ICAAC/ICAAC__hyperlipidemia_110700.htm

This Study From Kaiser-Permanente HMO Did Not See Increase in Coronary Heart Disease in Short-Term Follow-Up of 4 Years For Patients on Protease Inhibitors
     Klein and colleagues monitored the rate of coronary heart disease (CHD) events in subjects on protease inhibitors. Hospital events for CHD were identified among 4541 HIV-infected members of the Kaiser Permanente Northern California HMO (cases) and among 41,000 randomly selected, age- and sex-matched members not known to be HIV-infected. 53 CHD events were found in HIV infected patients. The adjusted overall incidence rate was 5.5 CHD events per 1000 PY. The incidence was 5.2 for patients not on protease inhibitors and 5.8 for patients receiving protease inhibitors. The rate among controls was 2.8. The authors conclude that the data continue to suggest that PI use does not increase short-term risk for CHD, but the follow-up time is only 4 years in this study. The higher rate of CHD events among HIV infected persons not taking a PI (5.2 vs 2.8) compared to controls (people without HIV) is yet to be explained.

But, in This Study Sees Risk Factors Associated with Coronary Heart Disease in HIV Negative People
     Henry and colleagues evaluated lipid and metabolic status in a cohort of HIV-1-infected patients who achieved durable HIV-1 suppression on a regimen that included indinavir (ACTG 372A). The median time enrolled in ACTG 372A was 24 months. Samples of 100 study subjects had blood samples sent to a central laboratory for metabolic assays. The findings from this study include elevations in triglycerides and cholesterol, a low HDL, and a high rate of insulin resistance (56%). The authors conclude that the constellation of risk factors in this cohort appears to place them at increased risk for coronary heart disease.

In small study, higher rate of myocardial infarction seen in people on PI longer than 18 months
     Mary-Krause and colleagues studied the course of coronary heart disease in the French Hospital Database on HIV. Myocardial infarction (MI) was diagnosed in 54 of 19,795 patients men exposed to PI. Among these 54 subjects, 23 were diagnosed among subjects exposed less than 18 months to PI (group I), 18 among subjects exposed between 18 and 29 months (group II) and 13 among subjects exposed 30 months or more (group III). The incidence rate of MI per 10,000 PY was estimated as 8.9 in group 1, 19.2 in group 2 and 34.7 in group 3. The expected incidence in the general population with same gender and same age was 10.8 cases/10,000 PY. The authors conclude that there appears to be a dose-effect relationship, with a higher MI incidence rate among the cohort members exposed to PI for 18 months or more. The limitation of the study was that relatively few patients were exposed to PIs for more than 30 months. A longer follow-up is therefore warranted.