Many patients receiving highly active antiretroviral therapy (HAART), especially protease inhibitor (PI)-containing regimens (except atazanavir [ATV, Reyataz]), develop hyperlipidemia and hypertriglyceridemia. In HIV-uninfected individuals, there is evidence that hypertriglyceridemia is an independent risk for cardiovascular disease (CVD).

Data from the D:A:D (Data Collection on Adverse Events of Anti-HIV Drugs) study¹ showed increased incidence of myocardial infarction in HIV-infected patients on antiretroviral therapy. Although there have been a few studies concerning this issue over the past few years, it is still unknown whether HIV-infected patients are at increased CVD risk from elevated triglycerides.

This study from Dr. David Wohl's group (University of North Carolina, Chapel Hill) is a cross-sectional study of HIV-infected adults on stable non-nucleoside reverse transcriptase inhibitor (NNRTI)- and/or PI-containing regimens, with triglycerides >200 mg/dL and without diabetes. The researchers conducted fasting lipid profiling, 2-hour glucose tolerance testing to detect borderline diabetes or insulin resistance, and Vertical Auto Profile testing of low-density lipoprotein (LDL) and lipoprotein(a) cholesterol.

There were 52 patients enrolled; 93% were men, the mean age was 43 (range 28-59), 58% were non-white, and 79% were receiving a PI. The mean CD4+ cell count and HIV-RNA were 526 cells/mm³ and 34,366 copies/mL, respectively. The prevalence of CVD risk factors in this study seems high; 36% of the patients were smokers, 35% had hypertension, 30% had a family history of CVD, and almost 20% had previous CVD. Over 20% of the patients were overweight, as measured by body mass index (the mean was 27.4). However, this may simply reflect the demographics of the population in the southern United States.

The mean total cholesterol was 242, triglycerides were 499, direct LDL was 113, and high-density lipoprotein (HDL) was 40. The mean fasting insulin was 12.4 IU, and 2-hour glucose tolerance test was 110. The estimated 10-year CVD risk was calculated per National Cholesterol Education Program (NCEP) Adult Treatment Panel III guidelines. The scores for CVD are calculated using sex, total cholesterol, age, smoking habit, HDL level, and systolic blood pressure. The scores are then transformed into the 10-year risk of CVD based on the Framingham study. On average, patients in this study had 2 NCEP-defined risk factors (the most common ones are hypertension and smoking). The mean 10-year CVD risk for this cohort was 9%. One third of the cohort had a risk of >10%. When the investigators assumed that all the patients had quit smoking and redid the math, the risk dramatically decreased by 42%.

In summary, most patients on HAART with elevated triglycerides in this cohort also had elevated total cholesterol and borderline low HDL, and they had about a 9% chance of developing CVD over the next 10 years. Two other posters, both from the Swiss Cohort,^2,3 which looked at 5,907 patients (either receiving or not receiving HAART), show that the CVD risk factors were also high in their population, and that over 10% of the patients in their study were in the highest risk group for CVD (10-year risk >20%). When they analyzed whether the patients were treatment naive, pretreated (those that were on therapy but had stopped), or currently on HAART, they found an increasing calculated 10-year CVD risk with HAART (2.6%, 3.7%, and 6.4%, respectively).

While we are waiting for results from ongoing, large clinical trials measuring long-term CVD outcome in patients taking HAART, there is no doubt that we need to aggressively treat all the risk factors that can contribute to CVD in our patients. In patients predisposed to CVD, we need to carefully choose the regimen that is less likely to increase cholesterol and triglycerides. For patients on therapy with elevated cholesterol, switching from one PI that can cause hyperlipidemia to a newer PI, such as atazanavir, or an NNRTI may improve their lipid profiles. Providers need to also encourage lifestyle changes, such as smoking cessation, exercise, weight reduction and dietary modification, which have been shown to be effective at reducing CVD risk in the general population. When we have exhausted all measures, pharmacologic intervention with lipid-lowering agents should be considered.

Footnotes

1. Friis-Møller N, Weber R, D'Arminio Monforte A, et al. Exposure to HAART is associated with an increased risk of myocardial infarction: the D:A:D study. In: Program and abstracts of the 10th Conference on Retroviruses and Opportunistic Infections; February 10-14, 2003; Boston, Mass. Abstract 130.

2. Glass TR, Ungsedhapand C, Battegay M, et al. Prevalence of cardiovascular risk factors in HIV-infected individuals: the Swiss HIV Cohort Study. In: Program and abstracts of the XV International AIDS Conference; July 11-16, 2004; Bangkok, Thailand. Abstract WePeB5878.

3. Glass TR, Ungsedhapand C, Battegay M, et al. Impact of HAART on risk of cardiovascular disease: the Swiss HIV Cohort Study. In: Program and abstracts of the XV International AIDS Conference; July 11-16, 2004; Bangkok, Thailand. Abstract WePeB5899.