Dr. Inaba – I was recently watching a news program on TV and they had a story set in South Africa about the abuse of aids drugs; specifically protease inhibitors. They showed young male AIDs patients smoking the medicine instead of taking it orally. The men were obviously intoxicated and seemed to be habitated [sic]. The newscaster also pointed out that such behavior could lead to the development of HIV resistance to the drugs being abused. Do you see anything like this occurring in the USA and is there any relationship between protease inhibitors and any other drugs that have been abused in the past? Thank you.
Howard Darvey, PharmD. June 1, 2009
Dr. Darvey,
Thank you so much for your inquiry on June 1st. Please excuse this much belated response. My delay is in part due to the fact that I have yet to personally hear of anyone abusing protease inhibitor medications in this country. As you know, these medications are prescribed to treat HIV/AIDS contagion and are vital to controlling the proliferation of the virus in the body once infected. Since receiving your inquiry in June, I have continued to monitor medical reports for this unusual form of substance abuse. To date, abuse of AIDS medication(s) may be widespread in South Africa; this weird practice seems to be isolated to that part of the world. I haven’t found any other reports on protease inhibitor abuse and there appears to be very little scientific information on the psychopharmacology of these substances. Most of the readily accessible reports refer to a British Broadcasting Corporation News (BBC) dispatch, “Getting High on HIV Drugs in S Africa” which was released in December 2008.1 This is a very sketchy news report doesn’t even identify the specific protease inhibitor medication being abused. I was therefore faced with the following questions in order to effectively evaluate the BBC report so that I could respond to your inquiry:
- What specific protease inhibitor(s) is/are being abused?
- How are they were being abused? The BBC report mentioned that the medication was being mixed and smoked with marijuana and other drugs.
- Does any protease inhibitor reliably have attractive psychoactive effects or are the effects cited in the BBC report merely those of the marijuana and the other drugs that it is mixed with or are the reported psychoactive effects really just placebo effects?
- Is the medication(s) abused stable enough at its sublimation temperature (i.e. the temperature when a substance transforms from a solid to a gas) to be available via a smoking route of administration
First, what HIV/AIDS drug or drugs are being abused? A review of the University of California, San Francisco’s web site – “HIV InSite” for adverse effects of antiretroviral drugs revealed many of the medications listed possess side effects of fatigue, anorexia, insomnia, dizziness, or abnormal dreams.2 These were the only adverse effects listed that might remotely be considered attractive to some. However, these adverse effects are usually purported to be negative rather than attractive by those who experience them. Further, only a small fraction of those treated experience these adverse effects and so abusing them would not reliably achieve the desired mood alterations for all or even most users. One of these antiretroviral medications, efavirenz (Sustiva®) is said to cause abnormal dreams, drowsiness, dizziness and confusion as common adverse events. This is the best potential candidate for abuse as a psychoactive drug even though the effects are said to decrease within 2-4 weeks of therapy.
I did discover an ABC News report on the abuse of HIV drugs by South Africans that specifically names efavirenz as the medication being mixed with marijuana and smoked.3 This story was followed by a New York Daily News report that also identified efavirenz as the antiretroviral medication being abused in South Africa.4 The New York Daily News article is the only one I have found that mentions abuse of efavirenz here in the U.S. but this was merely a side comment attributed to Dr. Homayoon Khanlou, Chief of Medicine at the AIDS Healthcare Foundation who said that efavirenz was only occasionally abused in the U.S. and not a major issue. Dr Khanlou also stated that abuse of efavirenz is a major problem in South Africa and has been for several years. Various news reports state that efavirenz tablets are ground into powder and sometimes mixed with painkillers or marijuana, rolled into a cigarette and smoked. The claim is that over the last three years, efavirenz abuse has become so popular that one container of the medication sells for $60 and a whole pharmacy “shelf” is worth $3,000 on the South African black market. Since 600 mg. Sustiva® tablets are supplied in bottles of 30, this would be street value of $2 per tablet or more since generic efavirenz 600 mg. tablets come in packages of only 10 or 20 tablets. The drug gets to the black market by some HIV patients selling their own essential medication for profit and by diversion by health professionals for profit. Most commonly, patients and pharmacies are robbed of their efavirenz supplies.
Efavirenz abusers interviewed in a Nightline/South Africa Broadcasting Corporation documentary and by the BBC say that smoking the drug causes lightheadedness, dizziness, vivid dreams, hallucinations, depersonalization, relaxation, and helps them forget/ignore their problems. These effects are alleged to occur whether efavirenz is smoked by itself or mixed with other drugs and smoked. The mind altering effects of efavirenz are obviously attractive to substance abusers but are they reliable? Some web sites providing patient information on the side effects of efavirenz claim that its serious CNS actions are rare while others note an incidence of up to 25%.5,6 These sites also state that the side effects generally lessen and become easier to tolerate after a few months. However, prescribing information for Sustiva® provided by its manufacturer, Bristol-Myers Squibb list the CNS side effects as common.7 Abuse of efavirenz by smoking it probably adds to its ability to reliably produce pleasurable CNS effects – if it is molecularly stable enough at its sublimation temperature to be smoked.
I could not locate specific information regarding efavirenz’s sublimation temperature or its molecular stability in heat to know for certainty if it can be efficiently smoked. But I did find a study on the sublimation and stability of a structural analogue, DPC 963.8 The study was conducted to determine these properties for formula development and drying processes in the manufacture of new generations of antiretroviral AIDS drugs. This study indicates that efavirenz can indeed be effectively heated and converted to vapor by smoking without significantly destroying its molecular stability. Apparently the South African efavirenz abusers figured this out on their own a few years ago. I am always amazed by the cleverness of folks looking for new ways to get high.
The real question is why is a medication to treat HIV/AIDS being abused in South Africa where other drugs of abuse are readily available? This is especially puzzling because the descriptions of altered states obtained by efavirenz don’t stack up favorably to descriptions of cocaine, heroin, ecstasy, methamphetamine or even OxyContin® abuse. Some have suggested that efavirenz is cheap and plentiful in South Africa due to our nation’s compassionate desire to make antiretroviral treatment available to indigent populations.1 This doesn’t appear to be the reason because black market prices for the drug are growing rapidly in South Africa and street prices are now high enough to tempt AIDS patients to sell their vital medication for the money. Maybe, we are all grossly underestimating the psychoactive properties of smoking efavirenz.
Some concerns raised about smoking efavirenz are potential harm to nasal passages and lung tissues. However, the greatest concern about its diversion for abuse purposes is the potential development of new HIV viral strains that will be resistant to antiretroviral treatments.
As of today, I have found no evidence of efavirenz abuse anywhere other than South Africa, thank goodness!
Thanks for turning me on to this story, it really got me thinking.
Darryl S. Inaba, Pharm.D., CADC III
August 2009
References
1. Marwaha A (2008), Getting high on HIV drugs in S Africa, BBC News, http://news.bbc.co.uk/2/hi/africa/7768059.stm accessed 6/2/09
2. McNicholl I (2007), Adverse effects of antiretroviral drugs, UCSF HIV InSite, http://hivinsite.ucsf.edu/InSite?page=ar-05-01 accessed 7/14/09
3. Sciutto J (2009), ‘No turning back’: teens abuse HIV drugs, ABC News 4/6/09; http://www.abcnews.go.com/print?id=7227982 accessed 7/21/09
4. Black R (2009), Abusing the anti-HIV/AIDS drug efavirenz could have devastating results for South Africans, NY Daily News 4/7/09, http://www.nydailynews.com/lifestyle/health/2009/04/07/2009-04-07_abusing_the_antihiv… accessed 7/25/09
5. Puzantian T (2009), Central nervous system adverse effects with efavirenz, Medscape.com, http://www.medscape.com/viewarticle/439816_3 accessed 7/18/09
6. (2008), CNS side effects: mood changes, anxiety, dizziness, sleep disturbances – Associated drugs: efavirenz (Sustiva), Atripla (contains efavirenz), i-base, http://www.i-base.info/guides/side/efavirenz.html accessed 7/14/09
7. Physicians’ Desk Reference (2007), Sustiva, PDR Edition 61, page 937
8. Xie M, Ziemba TM and Maurin MB (2003), Sublimation characterization and vapor pressure estimation of an HIV nonnucleoside reverse transcriptase inhibitor using thermogravimetric analysis, AAPS PharmSciTech, 4(2): 99-108
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