Starting HIV treatment with a CD4 cell count below 350 cells/mm3 is associated with a higher likelihood of arterial stiffness, an early warning sign for heart disease, US investigators report in the online edition of AIDS.
They found that HIV-positive individuals who started antiretroviral therapy when their CD4 cell count was below 350 cells/mm3 – the current recommended threshold for the initiation of such treatment – were significantly more likely to have evidence of arterial stiffness than patients who started treatment at higher CD4 cell counts.
Arterial stiffness is an early sign of the development of atherosclerosis – or hardening of the arteries, an important risk factor for cardiovascular disease.
Increased rates of cardiovascular disease have been observed in patients with HIV, but the reasons for this are controversial. Possible explanations include the direct effects of HIV, inflammation, life-style-related factors, or the side-effects of some anti-HIV drugs.
The SMART treatment interruption study found that HIV-positive individuals who were taking HIV treatment and had a CD4 cell count above 350 cells/mm3 had lower rates of cardiovascular disease than patients with lower CD4 cell counts who were not taking treatment.
Therefore, to reduce the risk of cardiovascular disease and other serious illnesses, treatment guidelines recommend that patients should start taking HIV therapy before their CD4 cell count falls below 350 cells/mm3.
Some doctors believe that starting treatment at even higher CD4 cell counts could have additional health benefits.
Accordingly, investigators from San Francisco involved in the Study of the Consequences Of the Protease Inhibitor Era (SCOPE) research group undertook a cross-sectional study involving 80 HIV-infected patients.
The investigators hypothesised that patients who started treatment when their CD4 cell count was below 350 cells/mm3 would have greater arterial stiffness than those who started therapy with a better-preserved immune system.
Arterial stiffness was measured using pulse wave analysis (Axis@75) and pulse wave velocity in the carotid-femoral artery.
The patients had a median age of 47, and there was a high prevalence of traditional risk factors for cardiovascular disease. All were taking antiretroviral therapy, and all had had an undetectable viral load for at least twelve months.
Most (65) of the patients started antiretroviral therapy when their CD4 cell count was below 350 cells/mm3.
Individuals starting antiretroviral therapy at lower CD4 cell counts had been infected with HIV for longer (17 vs 6 years, p < 0.001), had lower current CD4 cell counts (459 vs 785 cells/mm3, p < 0.001), and lower nadir CD4 cell counts (85 vs 494 cells/mm3, p < 0.001) than those who started treatment when their CD4 cell count was above 350 cells/mm3.
Arterial stiffness, measured by Axis@75, was associated with a number of traditional risk factors including age, blood pressure, the use of medication to control blood pressure, smoking, and family history.
HIV-related factors were also significant, including longer duration of HIV infection (p = 0.006), longer duration of treatment with a protease inhibitor (p = 0.05), and the initiation of antiretroviral therapy with a CD4 cell count below 350 cells/mm3 (p < 0.001).
Subsequent analysis that controlled for potentially confounding factors showed that starting antiretroviral therapy with a CD4 cell count below 350 cells/mm3 was the only HIV-related factor significantly associated (p = 0.003) with arterial stiffness measured by Axis@75.
The investigators emphasise that neither the duration of HIV therapy, nor the use of specific classes of antiretroviral drug were associated with this measure of arterial stiffness.
In addition, the researchers found that there was a relationship between diminished pulse wave velocity and the initiation of HIV treatment with a CD4 cell count below 350 cells/mm3 (p = 0.03).
“Nadir CD4 cell count was a strong and consistent predictor of both pulse wave velocity and arterial stiffness,” comment the investigators; “this association appeared to be independent of other important clinical factors that are known to influence measures of arterial stiffness such as age, blood pressure, and diabetes mellitus.”
They conclude, “our data may provide initial evidence that earlier initiation of antiretroviral therapy before low CD4 cell counts occur may be a means of reducing cardiovascular risk among individuals with HIV infection. Prospective studies are needed to evaluate potential beneficial effects of highly active antiretroviral therapy initiation at higher CD4 cell counts on cardiovascular risk.”
Ho JE et al. Initiation of antiretroviral therapy at higher nadir CD4 T-cell counts is associated with reduced arterial stiffness in HIV-infected individuals. AIDS, advance online publication: DOI: 10. 1097/QAD. 0b013e32833bee44, 2010.