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Response to Newly Prescribed Lipid-Lowering Therapy in Patients With and Without HIV Infection

Michael J. Silverberg, PhD, MPH; Wendy Leyden, MPH; Leo Hurley, MPH; Alan S. Go, MD; Charles P. Quesenberry Jr., PhD; Daniel Klein, MD; and Michael A. Horberg, MD, MAS
[+] Article and Author Information

From Kaiser Permanente Northern California, Oakland, and University of California at San Francisco, San Francisco, California.


Results were presented in poster form at the 14th Conference on Retroviruses and Opportunistic Infections, Los Angeles, California, 25–28 February 2007 (#814).

Grant Support: By GlaxoSmithKline.

Potential Financial Conflicts of Interest: None disclosed.

Reproducible Research Statement:Study protocol and data set: Not available. Statistical code: Available from Dr. Silverberg (e-mail, Michael.J.Silverberg@kp.org).

Requests for Single Reprints: Michael J. Silverberg, PhD, MPH, Division of Research, Kaiser Permanente of Northern California, 2000 Broadway, Oakland, CA 94612; e-mail, Michael.J.Silverberg@kp.org.

Current Author Addresses: Dr. Silverberg, Ms. Leyden, Mr. Hurley, Dr. Go, Dr. Quesenberry, and Dr. Horberg: Division of Research, Kaiser Permanente of Northern California, 2000 Broadway, Oakland, CA 94612.

Dr. Klein: Hayward Medical Center, Kaiser Permanente of Northern California, 27400 Hesperian Boulevard, Hayward, CA 94545.

Author Contributions: Conception and design: M.J. Silverberg, L. Hurley, D. Klein.

Analysis and interpretation of the data: M.J. Silverberg, W. Leyden, L. Hurley, A.S. Go, C.P. Quesenberry Jr., D. Klein, M.A. Horberg.

Drafting of the article: M.J. Silverberg.

Critical revision of the article for important intellectual content: M.J. Silverberg, W. Leyden, L. Hurley, A.S. Go, C.P. Quesenberry Jr., D. Klein, M.A. Horberg.

Final approval of the article: M.J. Silverberg, W. Leyden, L. Hurley, A.S. Go, C.P. Quesenberry Jr., D. Klein, M.A. Horberg.

Statistical expertise: M.J. Silverberg, C.P. Quesenberry Jr.

Obtaining of funding: M.J. Silverberg.

Administrative, technical, or logistic support: M.J. Silverberg.

Collection and assembly of data: M.J. Silverberg, W. Leyden.


Ann Intern Med. 2009;150(5):301-313. doi:10.7326/0003-4819-150-5-200903030-00006
Text Size: A A A

Background: Antiretroviral agents, particularly protease inhibitors (PIs), may adversely affect lipid levels in patients with HIV infection. However, it is not known whether HIV-associated dyslipidemia is more difficult to treat.

Objective: To compare the effectiveness and safety of lipid-lowering therapy in patients with and without HIV infection.

Design: Retrospective cohort study.

Setting: Integrated health care delivery system from 1996 to 2005.

Patients: 829 patients with HIV infection and 6941 patients without HIV infection beginning lipid-lowering therapy for elevated low-density lipoprotein cholesterol or triglyceride levels.

Measurements: Percentage change in lipids within 12 months and adverse liver- and muscle-related clinical and laboratory events.

Results: Compared with patients without HIV infection, patients with HIV infection beginning statin therapy had smaller reductions in low-density lipoprotein cholesterol levels (25.6% vs. 28.3%; P = 0.001), which did not vary by antiretroviral therapy class. Patients with HIV infection beginning gemfibrozil therapy had substantially smaller reductions in triglyceride levels than patients without HIV infection (44.2% vs. 59.3%; P < 0.001), and reductions with gemfibrozil varied by antiretroviral therapy class (44.0% [P = 0.001] in patients receiving PIs only, 26.4% [P < 0.001] in patients receiving PIs and nonnucleoside reverse transcriptase inhibitors [NNRTIs], and 60.3% [P = 0.94] in patients receiving NNRTIs only). Rhabdomyolysis was diagnosed in 3 patients with HIV infection and 1 patient without HIV infection. No clinically recognized cases of myositis or myopathy were observed. The risk for laboratory adverse events was low (<5%), although it was increased in patients with HIV infection.

Limitations: Laboratory measurements were not uniformly performed according to HIV status, and adequate fasting before lipoprotein testing could not be verified. Results may not be completely generalizable to uninsured persons, women, or certain racial or ethnic minorities.

Conclusion: Dyslipidemia, particularly hypertriglyceridemia, is more difficult to treat in patients with HIV infection than in the general population. However, patients with HIV infection receiving NNRTI-based antiretroviral therapy and gemfibrozil had triglyceride responses similar to those in patients without HIV infection.

Funding: GlaxoSmithKline.

Figures

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Figure 1.
Study flow diagram.

dx = diagnosis; KPNC = Kaiser Permanente of Northern California; HIV+ = HIV-infected; HIV− = HIV-uninfected; LDL = low-density lipoprotein; LLT = lipid-lowering therapy.

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Figure 2.
Changes in LDL cholesterol and triglyceride levels in study patients.

Data for all lipid tests in 50 randomly selected participants in each group are shown. We obtained mean percentage and absolute changes in lipid levels from unadjusted linear regression models for the overall study sample, comparing the first and last lipoprotein measurements within 1 year of lipid-lowering therapy initiation. To convert values to mg/dL, divide by 0.0259 for LDL cholesterol and 0.0113 for triglycerides. LDL = low-density lipoprotein.

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Figure 3.
Adjusted percentage changes in LDL cholesterol and triglyceride levels within 12 months of lipid-lowering therapy.

Results are based on linear regression with adjustment for age, sex, year, lipid-lowering therapy class, months of follow-up, baseline LDL cholesterol and triglyceride levels, number of coronary disease risk factors, past coronary disease or diabetes diagnoses, and hepatitis B or C infection. Model for any statin use is also adjusted for dose-equivalents of different individual statins and concomitant use of other lipid-lowering therapy classes. Model for gemfibrozil is also adjusted for medication dose and concomitant use of other lipid-lowering therapy classes. Ator = atorvastatin; HIV+ = HIV-infected; HIV− = HIV-uninfected; LDL = low-density lipoprotein; Lova = lovastatin; Prav = pravastatin; Simv = simvastatin.

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Summary for Patients

Response to Cholesterol-Lowering Drugs in Patients With and Without HIV Infection

The summary below is from the full report titled “Response to Newly Prescribed Lipid-Lowering Therapy in Patients With and Without HIV Infection.” It is in the 3 March 2009 issue of Annals of Internal Medicine (volume 150, pages 301-313). The authors are M.J. Silverberg, W. Leyden, L. Hurley, A.S. Go, C.P. Quesenberry Jr., D. Klein, and M.A. Horberg.

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