Cardiovascular and cerebrovascular events in patients treated for HIV infection

Metabolic abnormalities associated with HIV infection, including dysglycemia and hyperlipidemia, are increasingly prevalent, and there is concern about the possibility of an association with accelerated cardiovascular and cerebrovascular disease. In the current study, the relation between the risk of such disease and the use of antiretroviral therapy was evaluated.

Researchers conducted a retrospective study of the risk of cardiovascular disease among the 36,766 patients who received care for HIV at Veterans Affairs facilities between January 1993 and June 2001. Compared with typical patients with HIV in the United States, members of the VA cohort receiving services were more likely to be black (52.4%) and far more likely to be men (98.1%). The cohort was also slightly older (17.6% were less than 35 years old) and had less severe illness (36.7% were asymptomatic and had more than 500 CD4 cells/mm3 at diagnosis). A total of 23.9% had been previously treated at a VA facility for diabetes, hypertension, hyperlipidemia, or smoking, and 6.6% had been treated at a VA facility for vascular disease.

For antiretroviral therapy, 70.2% of patients received nucleoside analogues (NA), 41.6% received protease inhibitors (PI), and 25.6% received non-nucleoside reverse transcriptase inhibitors (NNRTI) for a median of 17 months, 16 months, and 9 months, respectively. Approximately 1,000 patients received combination therapy with a PI for at least 48 months, and approximately 1,000 patients received combination therapy with an NNRTI for at least 24 months.

Overall, there were 1,207 admissions for cardiovascular disease, 1,764 admissions for cardiovascular or cerebrovascular disease, and 2,006 admissions for or deaths from cardiovascular or cerebrovascular disease. Between 1995 and 2001, the rate of admissions for cardiovascular disease decreased from 1.7 to 0.9 per 100 patient-years, and the rate of death from any cause decreased from 21.3 to five deaths per 100 patient-years. Patient-level regression analyses indicated that there was no relation between the use of NAs, PIs, or NNRTIs and the hazard of cardiovascular or cerebrovascular events. However, the use of antiretroviral drugs was associated with a decreased hazard of death from any cause.

The fear of accelerated vascular disease need not compromise antiretroviral therapy over the short term, researchers concluded. Large increases in antiretroviral drug use by a large population of HIV-positive VA patients during the second half of the 1990s were accompanied by small decreases – rather than the feared increases – in the rates and hazards of cardiovascular and cerebrovascular events. However, the researchers cautioned that prolonged survival among HIV-infected patients means that longer-term observations and analyses are required.

Bozzette SA, Ake CF, Tam HK et al. Cardiovascular and cerebrovascular events in patients treated for human immunodeficiency virus infection. N Engl J Med 2003 Feb 20;348(8):702-10

Comment

Conflicting results from studies looking at CVD in HIV-positive patients – notably the NEJM article above showing no increase in CVD and the recently presented data from D:A:D study showing an apparent cumulative risk for each year of treatment – continue to cause confusion about the additional real risk that HIV treatment may add. The risk/benefit of HIV treatment is clearly in favour of treatment for people with low CVD risk but not so easily quantified when CVD risk is high (male, >45 years, family history, smoking, high fat diet, low exercise – and importantly contribution of increased lipids from ARV treatment.

Guidelines now generally include assessment for CVD risk prior to therapy, but give little practical help for how this should then related to decisions to prescribe treatment. Of concern is the finding that half the patients in the UK initiating HIV therapy for the first time last year, failed to have simple blood pressure recorded.