Erectile dysfunction drugs. Sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis) are commonly prescribed drugs for complaints of erectile dysfunction (ED). It is important to be aware that concentrations of these agents—especially sildenafil—are elevated when co-administered with PIs.10 ED drugs should be used less frequently and in lower doses by patients taking this classification of HIV medicine.

Migraine headache medications. Drug levels of such ergot alkaloid derivatives as ergotamine (Cafergot) and dihydroergotamine (Migranal) can be increased if co-administered with PIs. This combination of medications should be avoided. The anticonvulsant topiramate (Topamax, Topiragen) can be given instead, because it does not interfere with HIV medications that depend on liver metabolism.10

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Heart medicine. Many patients are prescribed calcium-channel blockers (CCBs) for hypertension, angina, and cardiac rhythm disorders. PIs can increase the serum levels of these drugs. Close monitoring of individuals using both of these medications is recommended.

Most of the agents taken for heart disease do not interact with NNRTIs or PIs. CCBs, however, need to be used with caution. Amlodipine (Norvasc) has minimal CYP3A4 metabolism and is safe to prescribe. Blood levels of cardizem (Diltiazem) and verapamil (Calan, Covera, Isoptin, Verelan) may be increased by concomitant use with antiretrovirals and should be avoided.10

Recreational and street drugs. Few studies show the interaction between HAART therapy and recreational drug use. There is some evidence that ritonavir can increase the concentration of the drug ecstasy (MDMA), which can lead to high levels of agitation, seizures, and increased heart rate.13 It is important to establish a respectful relationship with a patient taking HIV medications so recreational drug use can be discussed in a constructive manner.

Methadone. Levels of methadone are reduced by the NNRTIs efavirenz and nevirapine. The plasma concentration of methadone may be reduced to a level at which withdrawal symptoms start to become evident. This occurs because methadone undergoes hepatic biotransformation by the CYP450 system.14 Since this is the same system used by many HIV antiretroviral medications, interactions between the two medications can cause the patient to feel as if their methadone is either too strong or weakened. Collaboration between the patient’s methadone clinic and the prescribing practitioner is vital.

Herbal therapies. St. John’s wort, an herbal supplement used to treat depression, is associated with a significant decrease in levels of indinavir (Crixivan). St John’s wort should not be used with HIV medications in the NNRTI or PI classification.15


Obviously, no clinician can memorize every possible drug interaction. Having worked with HIV patients and medications every day for years, I still find it difficult to keep up with the ever-expanding list of interactions. A Web site created by the University of California, San Francisco, offers a useful database of antiretroviral drug interactions that have been reported in published articles, abstracts from major conferences, or presented to the FDA (generally reflected in product labeling). The database is searchable by antiretroviral drug, interacting drug, or interacting drug class.16

Mr. Graham is a family nurse practitioner with Associates in Family Health Care, a rural health clinic that provides care to a medically underserved population in Westmoreland County Pennsylvania.


    1. Centers for Disease Control and Prevention. Diagnoses of HIV infection and AIDS in the United States and dependent areas, 2009. 
    2. National Institute of Allergy and Infectious Diseases. Classes of HIV/AIDS antiretroviral drugs. 
    3. AIDS Education and Training Centers. Drug-drug interactions with HIV-related medications. 
    4. HIV drug-drug interactions. 
    5. Department of Health and Human Services. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. January 10, 2011; 1-166. 
    6. Centers for Disease Control and Prevention. Updated guidelines for the use of rifabutin or rifampin for the treatment and prevention of tuberculosis among HIV-infected patients taking protease inhibitors or nonnucleoside reverse transcriptase inhibitors. MMWR Morb Mortal Wkly Rep. 2000;49:185-189.
    7. National AIDS Treatment Advocacy Project. HIV has as much impact on heart health as traditional risk factors.
    8. Dubé MP, Sprecher D, Henry WK, 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. Clin Infect Dis. 2000;31:1216-1224.
    9. Farber EW, McDaniel JS. Clinical management of psychiatric disorders in patients with HIV disease. Psychiatr Q. 2002;73:5-16.
    10. Rainey PM. HIV drug interactions: the good, the bad, and the other. Ther Drug Monit. 2002;24:26-31.
    11. Columbia University HIV Mental Health Training Project. Psychiatric medications and HIV antiretrovirals: a guide to interactions for clinicians.
    12. AIDS Education and Training Centers. Antiretroviral medications and hormonal contraceptive agents.
    13. Antoniou T, Tseng AL. Interactions between recreational drugs and antiretroviral agents. Ann Pharmacother. 2002;36:1598-1613.
    14. Pinzani V, Faucherre V, Peyriere H, Blayac JP. Methadone withdrawal symptoms with nevirapine and efavirenz. Ann Pharmacother. 2000;34:405-407.
    15. Piscitelli SC, Burstein AH, Chaitt D, et al. Indinavir concentrations and St John’s wort. Lancet. 2000;355:547-548.
    16. HIV InSite. Database of antiretroviral drug interactions.

    All electronic documents accessed July 15, 2011.