October 30, 2001
There is creeping evidence, both from large database studies and assessments of plaques in carotid intima (the lining of the arteries to the brain), that people with HIV may be at increased risk of cardiovascular disease. Several factors may play a role in this. Smoking, for instance, may be more common among HIV-positive individuals with chronic inflammatory conditions (such as chronic viral infections). People on therapy may have increased coaguability (blood that clots easier) and, of course, therapy may drive elevations in cholesterol (especially the higher-risk low density and very low density [LDL and VLDL] types) and triglycerides -- both independent risk factors for heart disease in the general population. Lipodystrophy with truncal obesity, insulin resistance and, in some patients, diabetes mellitus are additional risk factors.
One large cohort study set up to examine cardiovascular risk is called DADs. This is a multinational collaboration in Europe looking at over 20,000 persons on eleven databases. The cohort was set up two years ago and hopes to present their first event data over the next year or so. The analysis presented at ECCAT focused on known cardiovascular risk factors and their relationship with disease and treatment at cohort recruitment. Data from the first nine cohorts including 17,850 patients were presented. The characteristics of the participants included an average age of 39 years, 24% female, 22% injection drug users, 25% with AIDS and a median CD4 count of 430/mm3 and viral load <500 copies/ml (i.e., more than half the cohort were <500 copies/ml). With regard to medication use for HIV, 73% were protease-inhibitor exposed, 89% NRTI-exposed and 40% NNRTI-exposed. Twelve percent were treatment-naive, 10% treatment-experienced but off treatment, 18% on NRTIs alone, 18% on NRTI and NNRTI and 42% on NRTI and PI regimens. NRTI exposure was for a median of 3.6 years, PIs for 2.8 years and NNRTIs for 1.3 years -- consistent with evolving treatment patterns.
Risk factors for cardiovascular disease under evaluation include cholesterol >6.2 mmol/l (~220mg/dl), triglycerides >2.3mmol (~200mg/dl), obesity (body mass index >30), smoking, hypertension, diabetes and both past and family history of cardiovascular disease. Extraordinarily, 52% of the cohort were smokers, with high cholesterol in 22%, high triglycerides in 33%, hypertension in 8%, obesity in 4% and diabetes in 3%.
Analysis by antiretroviral use indicated a rising risk for high cholesterol. Treatment-naive and off-therapy patients had the lowest risk of developing high cholesterol. Patients on NNRTIs had a 22% risk. Patients on PIs had a 25% risk. Those taking both a PI and NNRTI with NRTIs had the greatest risk of developing high cholesterol at 44%. Differences in risk between naive and treated patients were significant in a multivariate model, with relative risk lowest for those on a regimen of NRTIs alone via NNRTI and highest for those on triple-class therapy and with those on PIs somewhere in between. Analysis by drugs to look at boosted versus unboosted PI and between NNRTIs are underway.
Disease factors also played a role. In the past it was recognized that individuals with more advanced HIV disease had low cholesterol (especially the "good" HDL) and (especially if wasted) high triglycerides. In the DADs cohort, with every two-fold lower CD4 cell count, and every log10 higher viral load, the chance of having a high cholesterol fell. That is to say, more advanced CD4 decline and higher viral load reduced the risk of a high triglyceride. These findings were independent of treatment effects; both treatment and disease markers contributed to risk. It now remains to be seen if these markers are harbingers of a future epidemic of heart disease, a small change in risk, or of no clinical relevance to persons with HIV.