October 28, 2013
The risk of a heart attack in a person with HIV whose CD4+ cell count has never dropped below 500 cells/mm3 is similar to the risk for an HIV-uninfected person, according to the results of a major U.S. study published online last week in the Journal of Acquired Immune Deficiency Syndromes. The results lend new credence to the view that HIV-infected people should initiate potent antiretroviral therapy as soon as possible following their diagnosis.
Although cardiovascular disease is known to be a significant contributor to mortality among people with HIV, the interplay of various risk factors -- and the role of HIV and immunodeficiency itself -- has not been conclusively determined. Michael Silverberg, M.D., M.P.H., and colleagues from Kaiser Permanente designed this study to reach greater clarity regarding the effect of HIV-related immunodeficiency on myocardial infarction (MI) risk.
The study centers around a diverse cohort of 252,150 adult patients (22,081 of whom were living with HIV) who were members of Kaiser's Northern California or Southern California health plan. HIV-infected patients were demographically matched with HIV-uninfected counterparts. The data span most of the combination antiretroviral therapy era: 1996 through 2009.
The overall number of heart attacks observed in the study was relatively low: 280 among the 22,081 HIV-infected patients and 2,064 among the 230,069 HIV-uninfected patients. After adjusting for potential confounders, the overall MI risk was found to be 44% higher for people with HIV than their HIV-uninfected counterparts.
The major finding of the research was that an HIV-infected person's nadir CD4+ cell count appeared to be independently associated with MI risk -- and that, in fact, nadir CD4+ cell count was the only HIV-specific factor that accounted for a higher MI risk among study participants with HIV.
When stratifying patients by nadir CD4+ cell count, a statistically significant trend (P = .002) emerged:
The 95% confidence interval for the group of patients with a nadir CD4+ cell count above 499 ranged from a relative risk of 0.96 to 1.45. Statistically, this suggests no significant difference in MI risk between the high-nadir subgroup and its HIV-uninfected counterpart. Overall, the researchers found an HIV-infected patient's relative risk for a MI dropped 12% for every 100 cells/mm3 increase in his or her nadir CD4+ cell count.
Similar trends were observed when examining patients' MI risk relative to their most recent CD4+ cell count, but the association was not nearly as strong as for nadir CD4+ cell count.
Meanwhile, no significant trend was observed when examining MI risk relative to a patient's most recent HIV viral load test result. Although an adjusted analysis discovered a trend (from 66% higher risk among those with a viral load of 10,000 copies/mL or higher down to 41% among those with a viral load below 500), it fell well short of statistical significance.
Interestingly, the researchers also found virtually no impact of antiretroviral therapy use on MI risk within their cohort in an adjusted analysis, although there was a subtle suggestion within the data that such benefits may not emerge until five or more years after HIV treatment initiation.
"The results suggest to me that our conceptualization of the contribution of HIV to cardiovascular disease is antiquated," said David Wohl, M.D., an associate professor of medicine at the University of North Carolina School of Medicine and the co-director of HIV services at the North Carolina Department of Corrections, who was not involved in this study. "Most persons in the U.S. now living with HIV had prolonged periods of uncontrolled viremia, and many were allowed to experience drifts in CD4 cell counts to less than 500/mm3. This study suggests that when counts drop, damage is done. As we have seriously started to treat patients earlier, my hope and expectation is that we will see a weakening of an association between HIV and cardiovascular disease."
"Antiretroviral therapy offers substantial health benefit to the individual," concurred Benjamin Young, M.D., Ph.D., the chief medical officer of IAPAC, the International Association of Providers of AIDS Care, who also was not involved in this study. "This study, and others like it, provide strong evidence that prevention of immune system damage not only prevents AIDS complications, but also may prevent illness from potentially lethal, non-communicable diseases. What we need to acknowledge is that the objection to broader access to life-saving antiretroviral therapy has less to do with evidence-based health science and more to do with dollars (or Euros, or rubles) and political will."
The full study, "Immunodeficiency and Risk of Myocardial Infarction Among HIV-Infected Individuals With Access to Care," was published online ahead of print on Oct. 23.
Myles Helfand is the editorial director of TheBody.com and TheBodyPRO.com.
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