A low CD4 cell count is a strong, independent risk factor for the development of cardiovascular disease for patients with HIV, investigators from the US HIV Outpatients Study (HOPS) report in the August 15th edition of Clinical Infectious Diseases (now online).
Taking HIV treatment was protective against the development of cardiovascular disease, and there was no evidence that treatment with any class of antiretroviral or individual anti-HIV drug increased the risk of such diseases.
“A lower CD4 cell count was independently associated with an increased risk of CVD [cardiovascular disease] event”, comment the investigators.
Their findings provide an important contribution to the ongoing debate about the best time to start HIV therapy, as they found higher rates of incident cardiovascular disease amongst patients with a baseline CD4 cell count below 500 cells/mm3.
They suggest that the inflammation caused by HIV infection is the likely cause for the increased risk of cardiovascular diseases seen for patients with a CD4 cell count below this threshold. “There is growing evidence that HIV or the inflammatory response to HIV infection contributes independently to the development of atherosclerosis”, write the authors.
The investigators performed this research because they wished to determine the causes of the higher rates of cardiovascular disease seen in people with HIV. They analaysed the importance of three possible causes: traditional risk factors, including smoking, diabetes, lipids, and family history; treatment with anti-HIV drugs; and CD4 cell count level.
A total of 2005 patients were included, all of whom were followed for at least a year between 2002 and 2009.
The patients were placed into one of four categories (low; moderate; moderately high; and high) according to the presence of traditional risk factors for cardiovascular disease and the consequent probability of experiencing a cardiovascular event in the next ten years.
Information was gathered on the use of antiretroviral therapy, as were data on nadir (lowest ever), baseline, and proximal (value at the time of an event) CD4 cell count.
Just over a third of patients (34%) were categorised as having a low risk of a cardiovascular event; 28% a moderate risk; 18% a moderately high risk; and 20% a high risk.
On entry to the study, the patients had a median age of 42 years, 76% were men, and 52% were white, 33% black and 12% Hispanic.
At baseline, median CD4 cell count was 395 cells/mm3, and the median nadir CD4 cell count was 197 cells/mm3. Just under a half of patients had a viral load below 400 copies/ml, the median baseline viral load being 419 copies/ml.
Median length of follow-up was 5.5 years, and during this time 7% of patients experienced a cardiovascular event.
Incidence was lowest for those with the fewest traditional risk factors (0.4 cases per 100 person years), and highest for those with the highest burden of traditional risk factors (3.0 per 100 person years, p < 0.001).
Traditional risk factors and a CD4 cell count below 500 were both significantly associated with an incident cardiovascular event (both p < 0.05).
“Of note”, write the investigators, “exposure to HAART [highly active antiretroviral therapy] during observation was…associated with reduced incidence of CVD [cardiovascular disease]” (p = 0.002).
“Multivariate” analysis then showed that, compared to a CD4 cell count above 500 cells/mm3, counts below 350 cells/mm3 and between 350 – 500 cells/mm3 were associated with a significantly increased risk of a cardiovascular event (p < 0.001 for trend).
The investigators calculated that “the attributable risk of incident CVD events for baseline CD4 cell count < 500 cells/mm3 was 25.6%, a value comparable to that for smoking tobacco and dyslipidemia and greater than the attributable risks associated with male sex, hypertension, or diabetes.”
These findings “support the need for randomised controlled trials to assess whether earlier initiation of ARVs [antiretrovirals] and avoidance of treatment interruptions will reduce the incidence of cardiovascular events”, conclude the authors.
Lichtenstein KA et al. Low CD4 T cell count is a risk factor for cardiovascular disease events in the HIV Outpatient Study. Clin Infect Dis, online edition, 2010.