Heart Break in Melbourne

[Treatment Horizons]

Heart Break in Melbourne
Cardiovascular disease studies focus on assessment, management & treatment
by Jeannie Wraight

Cardiovascular disease (CVD) has become a leading cause of illness and death in people living with HIV. CVD now accounts for twenty percent of deaths in HIV-positive people. Researchers and clinicians continue to piece together a complex picture of why the risk is so high, what causes various forms of CVD, who is at risk, and how we prevent and monitor CVD in people with HIV. Many important clinical studies were presented at the XX International AIDS Conference in Melbourne (AIDS 2014) that help inch us closer to deciphering the intricate puzzle of CVD pathogenesis and risks in people living with HIV.

A Statin for HIV Patients on Treatment
Dyslipidemia is a condition where there is an abnormal amount of lipids in the blood with elevated total or low-density lipoprotein (LDL) cholesterol (bad cholesterol) levels, or low levels of high-density lipoprotein (HDL) cholesterol (good cholesterol). Dyslipidemia is a risk factor for heart disease and is common in people with HIV, with reports in the U.S. of eighty-one percent in men and sixty-seven percent in women.

High LDL cholesterol is most effectively treated with statins. However, some statins are metabolized through and depend on the cytochrome P450 (CYP) system, including many commonly used ART agents, particularly protease inhibitors. Because these agents potentially interfere with statins that depend on the CYP system for metabolism when used in combination, certain statins have dose limitations, restrictions, or contraindications, particularly CYP34A, the principle isoenzyme metabolizing some statins.

In contrast, pitavastatin and pravastatin are not dependent on the CYP system for their metabolism and thus do not have any dose restrictions, limitations, or contraindications when used in combination with HIV protease inhibitors.

In the INTREPID trial (HIV patients treated with pitavastatin or pravastatin for dyslipidemia) 252 HIV-positive adults with dyslipidemia who were on stable ART for at least six months, and had a viral load of less than 200 copies/mL and a CD4 count of greater than 200 cells/mm3 were enrolled in the trial. All participants had fasting serum LDL-C of 130-220 mg/dL and triglycerides ≤400 mg/dL after the minimum 4-week washout/dietary stabilization period (inclusion criteria). Part of the exclusion criteria were those who were taking or had known CVD or diabetes mellitus.

There were 126 patients randomized to either pitavastatin 4 mg or pravastatin 40 mg in each treatment arm. Participants were stratified by the presence or the absence of hepatitis B or C.

Study results indicated that both pitavastatin 4 mg and pravastatin 40 mg both significantly reduced LDL-C after twelve and fifty-two weeks of treatment. Compared with pravastatin 40 mg, pitavastatin 4 mg demonstrated superior LDL-C reduction at Week 12 and was sustained at Week 52.

Researchers concluded that pitavastatin (4 mg) demonstrated superiority efficacy over pravastatin (40 mg) and is safe and effective in people with HIV with dyslipidemia including those on ritonavir-based regimens.

Worse CVD Risk Assessment and Management in Patients at HIV Specialty Clinics
Duke University researchers set out to determine if proper CVD risk management was occurring within HIV clinics, as the need for closer management and additional risk assessment for cardiovascular disease among HIV- positive people rises. A retrospective cohort study was performed comparing the management of people with HIV with dyslipidemia and high blood pressure (two prevalent risk factors for CVD) to HIV-negative patients of the same age, race and sex.

890 HIV-positive individuals with viral loads less than 400 copies/mL, a mean CD4 count of 552 cells/mL and 807 HIV-negative participants were recruited into the study. All participants were above age forty and had a mean Framingham 10 year risk score (measurement of CVD risk) of four percent. Those who had experienced a prior heart attack or cerebral vascular accident (CVA) were excluded.

An equal amount of participants from both arms had hypertension yet only 57.7 percent of the HIV-positive participants had been prescribed treatment versus 75 percent of the HIV-negative participants. Although hyperlipidemia was less common in people with HIV than those who were HIV-negative (18.1 percent vs. 26.4 percent), fewer HIV-positive people with hyperlipidemia (twenty-five percent) were prescribed statins than the negative controls (forty-two percent). The same was true for the prescription of aspirin (11.5 percent v. 22.8 percent), statins (15.1 percent v. 23.6 percent) and anti-hypertensives (35.6 v. 52.0 percent).

Researchers concluded that there was a lower degree of risk assessment and management of uncontrolled hypertension and hyperlipidemia in HIV-positive patients versus HIV-negative controls despite the necessity for closer monitoring of these patients.

“It is time for DHHS through the NIH, CDC and Office of AIDS Research to act to recognize and aggressively respond to the alarming and rising morbidity and mortality of cardiovascular disease in people living with HIV in the U.S. and worldwide. As noted recently at AIDS 2014 in Melbourne, the co-morbidities of HIV and CVD require more research and better prevention and treatment to avert a calamity of preventable loss and suffering,” said John C. Lewin, MD, President and CEO of the Cardiovascular Research Foundation.

Abstracts and presentations at AIDS 2014 clearly show a high degree of CVD risk among people living with HIV as well as a great need for further studies, closer management, more precise preventative measures, the identification of surrogate markers, clearer risk assessment tools and more inclusive and closer monitoring of these patients. How AIDS treatment activists push to make this as much a priority for dedicated investigative funding at the Office of AIDS Research is the question we will all have to wrestle with.

Jeannie Wraight is the editor-in-chief and co-founder of HIV and HCV Haven (www.hivhaven.com) and a blogger and writer for TheBody. com. She is a member of the Board of Directors of Health People, a community-based organization in the South Bronx and an advisor to TRW (Teach me to Read and Write), a community-based organization in Kampala, Uganda. She lives with her husband in the Bronx, New York.