"Increases in blood lipid levels have been widely reported in HIV patients treated with HAART, but until now there were no studies that included patients' lipid levels taken before they were infected with HIV," said study author Sharon A. Riddler, M.D., M.P.H., assistant professor, department of medicine, division of infectious diseases, University of Pittsburgh School of Medicine. "With access to such unique data, we were able to look at lipid levels across a broader spectrum in time and determine that after three years of HAART, the average total cholesterol and LDL cholesterol levels appear to be about where they were before HIV infection."
The researchers used data from the Multicenter AIDS Cohort Study (MACS), an ongoing 19-year-old National Institutes of Health-funded study of homosexual and bisexual men that to date has enrolled 5,622 participants, both HIV-positive and HIV-negative, in Pittsburgh at the University of Pittsburgh Graduate School of Public Health, Baltimore, Chicago and Los Angeles. Participants visit the study clinics every six months for an interview, physical examination and collection of blood samples.
For this study, researchers analyzed lipid levels of 50 MACS participants from whom blood samples were available from each of the following points in time: before HIV infection (preseroconversion), after infection but before initiation of HAART, at two points during HAART between 1997 and 1999 and at two points during HAART between 2000 and 2002.
HAART was defined as two or more nucleoside reverse transcriptase inhibitors (NRTIs) with at least one protease inhibitor (PI) or one nonnucleoside reverse transcriptase inhibitor (NNRTI); one NRTI with at least one PI and at least one NNRTI, a regimen containing ritonavir and saquinavir with one NRTI, or an abacavir-containing regimen of three or more NRTIs. Combinations of zidovudine and stavudine with either a PI or a NNRTI were not considered HAART.
Participants' average total cholesterol value before HIV infection was 201 mg/dL, average low-density lipoprotein (LDL) level was 122 mg/dL and high-density lipoprotein (HDL) level was 51 mg/dL – all within the normal range and consistent with the general population of adult men. Study participants' average age at preseroconversion was 35 years.
After HIV infection, but prior to initiation of HAART, average cholesterol levels dropped, consistent with results of previous studies. Participants' average total cholesterol decreased by 30 mg/dL, LDL by 22 mg/dL and HDL by 12 mg/dL.
Once HAART was started, total and LDL cholesterol levels began to rise again. After three years on HAART, participants' average total cholesterol was 221 mg/dL (a 20 mg/dL increase from baseline); average LDL was 121 mg/dL (a 1 mg/dL drop from baseline) and average HDL was 42 mg/dL (a 9 mg/dL drop from baseline). Participants' average age at the end of the period studied was 47 years.
"The results confirmed that yes, total cholesterol does increase with HAART, but in most cases it increases back to or near the pre-infection level, and in that sense it represents a return to normal," said Dr. Riddler. "The mean increase in total cholesterol of 20 milligrams noted in the study is consistent with a similar total cholesterol level increase in healthy men as they age, and would be considered a normal increase for the study participants over the 12-year span of our analysis."
Dr. Riddler cautions that it is possible the study results were affected by the timing of the analyses, and that additional studies are needed to determine whether a longer duration of HAART could result in further increases in cholesterol levels.
Another concern is the observation that while total and LDL lipid levels were relatively unchanged over three years on HAART, at the end of the study the participants' average triglycerides, levels were higher (225 mg/dL) and HDL levels were lower (42 mg/dL) than those in similar-aged men in the general population. In other studies, some HIV drugs have been associated with changes in glucose metabolism and the development of insulin resistance, a condition that may also contribute to heart disease risk.
"The fact that average triglyceride and HDL levels were at unhealthy levels at the completion of this study raises a red flag in terms of heart disease risk," said Dr. Riddler. "Until more is known, the current standard guidelines for treating high cholesterol should be followed in patients whose levels exceed the normal range. Also, with the ongoing collection of data through MACS, we will be able to look further into the effects of long-term triple-drug therapy and continue to refine treatments for patients with HIV."
This study was funded through a grant from the National Institutes of Health.
CONTACT:
Kathryn Duda
Frank Raczkiewicz
PHONE: 412-624-2607
FAX: 412-624-3184
E-MAIL:
DudaK@upmc.edu
RaczkiewiczFA@upmc.edu
Journal
JAMA