Prescribing of Contraindicated Protease Inhibitor and Statin Combinations Among HIV-Infected Persons

HIV-1 protease inhibitors (PIs) contribute to hyperlipidemia in persons treated for HIV infection. There are potential drug-drug interactions between PIs and some statins, which are drugs frequently used to treat hyperlipidemia. We performed a retrospective cohort study using the TennCare program to determine prescribing rates of contraindicated combinations of PIs and statins in HIV-infected persons in Tennessee and to assess changes in prescribing after publication of treatment guidelines. Computerized files identified adult patients with antiretroviral prescriptions and overlapping prescriptions for PIs and statins from January 1, 1996 through June 30, 2002. A subset of these combinations was defined as contraindicated based on published guidelines. Changes in patterns of prescribing after publication of preliminary treatment guidelines were examined using a mixed-effects logistic regression model. There were 3448 persons who received PIs during the study period. The proportion of PI users receiving statins increased from 3.5% during January 1996 through December 2000 to 7.9% during January 2001 through June 2002 (P < 0.001). Contraindicated PI-statin use decreased from 42.0% of combinations to 20.8% during the same periods (P < 0.001). Use of PIs and statins has increased in the adult TennCare population. Contraindicated combinations have decreased but remain unacceptably high.

[1]  H. Morgenstern,et al.  Lipid Screening in HIV-Infected Veterans , 2004, Journal of acquired immune deficiency syndromes.

[2]  D. Costagliola,et al.  Increased risk of myocardial infarction with duration of protease inhibitor therapy in HIV-infected men , 2003, AIDS.

[3]  Rodolphe Thiébaut,et al.  Combination antiretroviral therapy and the risk of myocardial infarction , 2003 .

[4]  W. K. Henry,et al.  Guidelines for the evaluation and management of dyslipidemia in human immunodeficiency virus (HIV)-infected adults receiving antiretroviral therapy: recommendations of the HIV Medical Association of the Infectious Disease Society of America and the Adult AIDS Clinical Trials Group. , 2003, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[5]  J. Bailey,et al.  Improvements in access to care for HIV and AIDS in a statewide Medicaid managed care system. , 2003, American Journal of Managed Care.

[6]  U. Iloeje,et al.  Increased use of lipid-lowering therapy in patients receiving human immunodeficiency virus protease inhibitors. , 2003, The American journal of cardiology.

[7]  D. Haas,et al.  Therapy with atazanavir plus saquinavir in patients failing highly active antiretroviral therapy: a randomized comparative pilot trial , 2003, AIDS.

[8]  M. Gill,et al.  Drug-induced rhabdomyolysis after concomitant use of clarithromycin, atorvastatin, and lopinavir/ritonavir in a patient with HIV. , 2003, AIDS patient care and STDs.

[9]  Leonardo Calza,et al.  Statins and fibrates for the treatment of hyperlipidaemia in HIV-infected patients receiving HAART , 2003, AIDS.

[10]  K. Squires,et al.  Results of a Phase 2 Clinical Trial at 48 Weeks (AI424-007): A Dose-Ranging, Safety, and Efficacy Comparative Trial of Atazanavir at Three Doses in Combination with Didanosine and Stavudine in Antiretroviral-Naive Subjects , 2003, Journal of acquired immune deficiency syndromes.

[11]  C. B. Hare,et al.  Simvastatin-nelfinavir interaction implicated in rhabdomyolysis and death. , 2002, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[12]  Amalio Telenti,et al.  Efficacy and safety of fluvastatin in hyperlipidemic protease inhibitor-treated HIV-infected patients. , 2002, AIDS.

[13]  M. Schambelan,et al.  Management of Metabolic Complications Associated With Antiretroviral Therapy for HIV‐1 Infection: Recommendations of an International AIDS Society‐USA Panel , 2002, Journal of acquired immune deficiency syndromes.

[14]  B. Gazzard,et al.  Pravastatin does not alter protease inhibitor exposure or virologic efficacy during a 24-week period of therapy. , 2002, Journal of acquired immune deficiency syndromes.

[15]  Christine Miller,et al.  Rhabdomyolysis due to probable interaction between simvastatin and ritonavir. , 2002, American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists.

[16]  C. Fichtenbaum,et al.  Pharmacokinetic interactions between protease inhibitors and statins in HIV seronegative volunteers: ACTG Study A5047 , 2002, AIDS.

[17]  M. Murty,et al.  Statins: rhabdomyolysis and myopathy. , 2002, CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne.

[18]  P. Hsyu,et al.  Pharmacokinetic Interactions between Nelfinavir and 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors Atorvastatin and Simvastatin , 2001, Antimicrobial Agents and Chemotherapy.

[19]  J. Fellay,et al.  For Personal Use. Only Reproduce with Permission from the Lancet Publishing Group , 2022 .

[20]  James P. Wilson,et al.  Rhabdomyolysis and HMG-CoA Reductase Inhibitors , 2001, The Annals of pharmacotherapy.

[21]  R. Leavitt,et al.  Indinavir did not increase the short-term risk of adverse cardiovascular events relative to nucleoside reverse transcriptase inhibitor therapy in four phase III clinical trials. , 2001, AIDS.

[22]  A. Telenti,et al.  Premature atherosclerosis in HIV-infected individuals – focus on protease inhibitor therapy , 2001, AIDS.

[23]  W. K. Henry,et al.  Preliminary guidelines for the evaluation and management of dyslipidemia in adults infected with human immunodeficiency virus and receiving antiretroviral therapy: Recommendations of the Adult AIDS Clinical Trial Group Cardiovascular Disease Focus Group. , 2000, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[24]  S. Staszewski,et al.  Incidence of myocardial infarctions in HIV-infected patients between 1983 and 1998: the Frankfurt HIV-cohort study. , 2000, European journal of medical research.

[25]  A Ammassari,et al.  Efficacy and tolerability of pravastatin for the treatment of HIV-1 protease inhibitor-associated hyperlipidaemia: a pilot study. , 2000, AIDS.

[26]  S. Hammer,et al.  Effects of protease inhibitors on hyperglycemia, hyperlipidemia, and lipodystrophy: a 5-year cohort study. , 2000, Archives of internal medicine.

[27]  D. Singer,et al.  Understanding physician adherence with a pneumonia practice guideline: effects of patient, system, and physician factors. , 2000, Archives of internal medicine.

[28]  M. Cabana,et al.  Why don't physicians follow clinical practice guidelines? A framework for improvement. , 1999, JAMA.

[29]  K. Henry,et al.  Atorvastatin and gemfibrozil for protease-inhibitor-related lipid abnormalities , 1998, The Lancet.

[30]  P. Kissinger,et al.  Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. , 1998, The New England journal of medicine.

[31]  G. Satten,et al.  Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. , 1998, The New England journal of medicine.

[32]  D A Savitz,et al.  Recall accuracy for prescription medications: self-report compared with database information. , 1995, American journal of epidemiology.

[33]  W. Applegate,et al.  TennCare--health system reform for Tennessee. , 1995, JAMA.

[34]  R E Johnson,et al.  Comparing Sources of Drug Data about the Elderly , 1991, Journal of the American Geriatrics Society.

[35]  W A Ray,et al.  Use of Medicaid data for pharmacoepidemiology. , 1989, American journal of epidemiology.

[36]  W. A. Edwards,et al.  A Comparison of Patient Drug Regimens as Viewed by the Physician, Pharmacist and Patient , 1981, Medical care.

[37]  B. Strom,et al.  Use of automated databases for pharmacoepidemiology research. , 1990, Epidemiologic reviews.