Abstract
Widespread diversion of antiretroviral (ARV) medications to illicit markets has recently been documented among indigent patients in South Florida. The recent approval of ARVs for pre-exposure prophylaxis (PrEP) has the potential to broaden these illicit markets, as high risk individuals seek ARVs without a prescription or medical supervision. Non-adherence among diverters and unsupervised use of ARVs for treatment or PrEP increase risks of treatment failure, drug resistance, and disease transmission. We report the scope of ARV diversion among substance using men who have sex with men in South Florida. Structured interviews (N=515) queried demographics, HIV status, mental distress, substance dependence, and sexual risks. HIV-positive participants answered questions about medical care, treatment, and ARV adherence and diversion. Median age was 39. Of 46.4% who were HIV-positive, 79.1% were prescribed ARVs. Of these, 27% reported selling/trading ARVs. Reasons for diversion were sharing/trading with friends, sale/trade for money/drugs, and sale/trade of unused medications. ARV diverters, compared to non-diverters, were more likely to be substance dependent (74.5% vs. 58.7%, p=.046) and have traded sex for money/drugs (60.8% vs. 32.6%, p<.001); and less likely to be adherent to ARVs (54.9% vs. 73.9%, p=.012). ARV diversion should be a particular concern in communities of high risk MSM, as uninfected men in such communities are likely to benefit most from PrEP but unlikely to have access to PrEP and necessary ancillary services through the health care system. The implications of diversion for increased risks of treatment failure, disease transmission, and PrEP failure should be carefully considered in developing policy and behavioral supports to scaling up treatment as prevention and PrEP.
Keywords: ARV, PrEP, MSM, diversion
Introduction
Widespread diversion – the unlawful channeling of regulated pharmaceuticals to illicit markets (Inciardi, Surratt, Kurtz, and Burke, 2006) – of antiretrovirals (ARVs) has recently been documented in South Florida among vulnerable, indigent patients who are targeted by pill brokers to trade their ARVs for money and/or drugs (Surratt, Kurtz, Cicero, O’Grady, & Levi-Minzi, 2013). Large scale diversion of ARVs has also been detected in several other locations (Surratt and Kurtz, 2013; Dorschner, 2005; Flaherty and Gaul, 2003; Glasgow, 1999; Associated Press, 1995), with law enforcement activities disrupting ARV diversion networks in no fewer than seven states. Beyond these organized profit-making enterprises, a few reports indicate that ARV diversion also occurs for the purposes of getting high on medications with known psychoactive properties (Grelotti, Closson, and Mimiaga, 2013; Inciardi, Surratt, Kurtz, and Cicero, 2007), or for non-prescribed pre- or post-exposure prophylaxis (PrEP/PEP) (Liu et al., 2008; Mansergh et al., 2010; Mimiaga, Case, Johnson, Safren, and Mayer, 2009). In this regard, emtricitabine/tenofovir, the only U.S. Food and Drug Administration (FDA) - approved medication for PrEP, is among the most frequently diverted ARV according to recent reports by both law enforcement and patients (Surratt & Kurtz, 2013; O’Grady, Surratt, & Kurtz, 2013). The selling and trading of ARVs is associated with non-adherence among diverters (Surratt et al., 2013), increasing the risk of treatment failure and disease transmission (Bangsberg et al., 2001), as well as drug resistance and PrEP failure among non-medically supervised end users (Hurt, Eron, and Cohen, 2011).
The recent approval by the FDA of ARVs for PrEP (FDA, 2012), together with the earlier issuance by the U.S. Centers for Disease Control and Prevention (CDC) of interim guidance for the clinical administration of PrEP (CDC, 2012; Smith et al., 2011), have the potential to broaden illicit markets for ARVs, as at-risk individuals - many lacking financial resources or health coverage (Curran and Crosby, 2013) - seek them without medical supervision or behavioral support. Although ARV diversion is also potentially a concern for unsupervised use by uninsured HIV-positive patients in search of ARVs for self-treatment, the widespread availability of low-cost treatment for HIV-positive patients in the US, together with the multiple and often complex treatment regimens for HIV infection, would appear to limit the use of diverted medications for this purpose. On the other hand, the approved PrEP regimen consists of a single well-recognized product, and the non-prescribed use of emtricitabine/tenofovir for prevention (e.g., “Methamphetamine, Truvada and Viagra [MTV] party packs,” “disco dosing,” “taking a T”) has been documented among high risk MSM since at least 2009 (D. Fawcett, personal communication, June 1, 2013; Philpott, 2013).
Here, we describe the diversion of ARVs among a highly vulnerable sample of HIV-positive substance-using men who have sex with men (MSM) as reported in interviews conducted during the period November 2008 through October 2011 as a part of their participation in an intervention trial.
Methods
The MSM Study is a randomized clinical trial of a behavioral intervention targeted to high risk substance using MSM in South Florida. Eligible men were ages 18 to 55 and reported recent (past 90 days) unprotected anal intercourse (UAI) with a non-monogamous partner(s); and met one or more of three substance use inclusion criteria: binge drinking (5 or more drinks) or drug use, excluding marijuana, at least three times, or marijuana use at least 20 days, in the past month.
Data reported here are drawn from standardized interviewer-administered baseline assessments (N=515) conducted between November 2008 and October 2011 that included measures of demographics, self-reported HIV status, sexual risk behaviors, and clinical measures of mental distress and substance dependence (Dennis, Titus, White, Unsicker, and Hodgkins, 2002). HIV-positive participants also answered questions about medical care and treatment; self-reported past month ARV adherence; and ARV diversion history. Reasons for diverting ARVs were assessed with open-ended responses that were coded into well-defined categories. Research protocols were approved by the University of Delaware’s (predecessor institution) and Nova Southeastern University’s Institutional Review Boards.
For the analyses presented here, descriptive statistics were used to characterize the study sample. Chi square and analysis of variance tests examined differences between HIV-positive participants with ARV prescriptions who had sold or traded their ARV medications compared to those who had not done so.
Results
Characteristics of the total sample and the sample of HIV-positive men with ARV prescriptions are shown in Table 1. Mean age of the full sample was 38.9 (SD 9.6); mean years of education, 13.8 (SD 2.4). Race/ethnicity: 48.5% White, 25.8% Hispanic, 21.0% African American/Caribbean, and 4.7% other. More than one quarter (25.8%) reported past year homelessness. Participants reported high levels of sexual risk behaviors, including an average of 13.3 (SD=18.6) anal sex partners and 22.6 (SD=35.4) UAI events in the past 90 days; 34.2% had traded sex for money or drugs in the past year. Majorities met clinical criteria for severe mental distress (57.9%) and substance dependence (62.1%), and had been victimized as minors (54.8%). Almost half (42.4%) were HIV positive. HIV-positive men with ARV prescriptions reported demographic and heath risk profiles that were similar to the full sample.
Table 1.
Baseline Characteristics of Substance Using MSM
Total Sample (N=515) | HIV + w/ARV prescrip. (N=189) | |||
---|---|---|---|---|
N | % | N | % | |
Demographics | ||||
Age (mean; SD) | 38.9 (9.6) | 43.4 (7.2) | ||
Education (mean; SD) | 13.8 (2.4) | 13.7 (2.3) | ||
Race/Ethnicity | ||||
Hispanic | 133 | 25.8% | 40 | 21.1% |
African American/Caribbean | 108 | 21.0% | 47 | 24.9% |
Caucasian | 250 | 48.5% | 93 | 49.2% |
Other | 24 | 4.7% | 9 | 4.8% |
Homeless in the past year | 133 | 25.8% | 52 | 27.5% |
Sex risk behavior (past 90 days) | ||||
Anal sex partners (mean; SD) | 13.3 (18.6) | 15.6 (19.8) | ||
UAI times (mean; SD) | 22.6 (35.4) | 26.1 (34.9) | ||
Traded sex (past 12 months) | 176 | 34.2% | 76 | 40.2% |
Health risk measures | ||||
Severe mental distress | 298 | 57.9% | 122 | 64.6% |
DSM-IVR substance dependence | 156 | 62.1% | 119 | 63.0% |
Victimized before age 18 | 282 | 54.8% | 101 | 53.4% |
Health care coverage | ||||
HIV-negative | 276 | 53.6% | - | |
Health care coverage | 117 | 42.4% | - | |
HIV-positive | 239 | 46.4% | - | |
Health care coverage | 206 | 86.2% | - | |
Receiving HIV medical care | 219 | 91.6% | - | |
Prescribed ARV medications | 189 | 79.1% | - |
Fewer than half (42.4%) of HIV-negative men had health care coverage, defined as any type of insurance or program to pay health expenses. Of the HIV-positive men, the large majority reported health care coverage (86.2%) and was currently receiving medical care (91.6%); 79.1% were prescribed ARV medication. Of the latter group (n=189), 27.0% (n=51) reported having ever sold and/or traded their ARVs (diverters); 19.0% had done so in the past year. Reasons for diversion were (more than one reason was permissible): share/trade with friends (n=32; 62.7% of diverters); sale/trade for money and/or drugs (n=19; 37.3%); donated leftover medications to a clinic or organization (n=10; 19.6%); and, sale/trade of medications that were no longer used (n=5; 9.8%). Two participants (3.9% of diverters) who donated their leftover medications to a clinic or organization did not engage in any other types of diversion activities. Such donations would likely not find their way into illicit markets, although the nature of the donee organizations is unknown.
Characteristics of participants with ARV prescriptions by diversion status are shown in Table 2. ARV diverters, compared to non-diverters, were more likely to be substance dependent (74.5% vs. 58.7%, p=.046) and to have recently traded sex for money/drugs (60.8% vs. 32.6%, p<.001); and less likely to be 90% adherent to their ARVs (54.9% vs. 73.9%, p=.012).
Table 2.
Correlates of ARV Diversion among MSM with Prescriptions (N=189)
Diverters (N=51) | Non-diverters (N=138) | ||||
---|---|---|---|---|---|
N | % | N | % | p | |
Demographics | |||||
Age (mean; SD) | 42.3 (6.9) | 43.8 (7.2) | 0.211 | ||
Education (mean; SD) | 13.6 (2.1) | 13.7 (2.3) | 0.932 | ||
Race/Ethnicity | |||||
Hispanic (ref.) | 9 | 17.6% | 31 | 22.5% | |
African American/Caribbean | 18 | 35.3% | 29 | 21.0% | 0.067 |
Caucasian | 22 | 43.1% | 71 | 51.4% | 0.644 |
Other | 2 | 4.0% | 7 | 5.1% | 0.881 |
Homeless in the past year | 17 | 33.3% | 35 | 25.4% | 0.276 |
Sex risk behavior (past 90 days) | |||||
Anal sex partners (mean; SD) | 14.7 (21.3) | 16.0 (19.3) | 0.695 | ||
UAI times (mean; SD) | 21.4 (23.8) | 27.9 (38.1) | 0.255 | ||
Traded sex (past 12 months) | 31 | 60.8% | 45 | 32.6% | <0.001 |
Health risk measures | |||||
Severe mental distress | 34 | 66.7% | 88 | 63.8% | 0.712 |
DSM substance dependence | 38 | 74.5% | 81 | 58.7% | 0.046 |
Victimized before age 18 | 30 | 58.8% | 71 | 51.4% | 0.367 |
90% adherent to ARVs | 28 | 54.90% | 102 | 73.9% | 0.012 |
Discussion
The diversion of ARVs is a largely unrecognized problem in the U.S., but has been documented in no fewer than seven states (Surratt and Kurtz, 2013). ARV diversion was also reported by more than one-quarter of HIV-positive participants with prescriptions in our intervention trial for high risk, substance using MSM. HIV-negative men in these high risk networks are among the highest priority for PrEP rollout (Smith et al., 2011), the most likely to benefit from PrEP (Curran & Crosby, 2013), and, if successfully targeted, the most likely to produce population-level improvements in the U.S. HIV epidemic in a cost-effective way (Juusola, Brandeau, Owens, and Bendavid, 2012). Moreover, MSM are known to be early adopters of new behavioral and biological HIV prevention technologies (Kippax, 2012). Indeed, the non-prescribed use of emtricitabine/tenofovir for prevention has been documented among high risk MSM since at least 2009 (D. Fawcett, personal communication, June 1, 2013; Philpott, 2013).
Although there is wide agreement among governmental agencies and scientists that individuals taking PrEP require frequent testing, regular health monitoring, and ongoing behavioral support (Koenig, Lyles, and Smith, 2013; Smith et al., 2011; Weber, Tatoud, and Fidler, 2010), MSM at highest risk for HIV infection are likely to have difficulty accessing these services. Data from our sample confirm others’ concerns (Curran & Crosby, 2013; Koenig et al., 2013) that MSM who would most benefit from PrEP suffer high rates of substance use and have limited access to health care. Only 42.4% of HIV-negative men in our study had any type of health care coverage. These vulnerabilities render them less likely to have access to prescribed PrEP, medical supervision and ancillary services. Nevertheless, this population of sexually active men is likely to have a high level of interest in PrEP (Krakower et al., 2012; Liu et al., 2008; Mimiaga et al., 2009), and, because their health and social vulnerabilities, to be at risk for attempting access to PrEP through non-medical channels.
Several limitations of the study design must be considered in evaluating the findings. First, the data rely on self-report, and some respondents may have refrained from reporting socially undesirable behaviors. In the present case, however, that would likely mean underreporting of diversion. Also, the prevalence of diversion among HIV-positive MSM found here is not necessarily generalizable to the overall population of HIV-positive MSM because of the eligibility requirements requiring recent substance abuse and UAI. Importantly, we did not collect data from HIV-negative men on their use of diverted ARVs; as such, our data confirm only the supply side of illicit markets. We do not know the characteristics of the end users of the diverted medications, nor their reasons for use.
Our findings indicate that street markets for ARVs approved for PrEP are already active. We have focused our analysis on the risks posed by ARV diversion to the successful rollout of PrEP rather than self-treatment for several reasons: 1) non-prescribed use of emtricitiabine/tenofovir for prevention has been documented among high risk MSM since well before the issuance of CDC guidance or FDA approval; 2) the great difference in access to health care between HIV-positive and HIV-negative MSM; over 90% of the HIV positive men in our high risk sample were in care; 3) the simplicity of the PrEP regimen compared to regimens for treatment of HIV infection and PEP; and 4) the lack of evidence for diverted ARVs being used for self-treatment. At the same time, the scale-up of treatment as prevention will potentially increase the supply of divertable ARVs.
As high risk MSM become more aware of the use of ARVs for PrEP, illicit markets may expand based on this new source of demand. In this informal illicit market sector, knowledge gaps, inconsistent ARV supplies and adherence, and lack of frequent testing and ongoing behavioral support may lead to sporadic use, unmonitored restarts, use when unknowingly infected, and, potentially, the use of counterfeit, ineffective, or compromised ARVs. Confusion over which drugs and dosages are approved for PrEP is also a concern (Weber et al., 2010). For PrEP to succeed in reducing HIV infections among at risk populations, expanded health care coverage, robust outreach programs, and access to services not directly related to HIV, including mental health and substance abuse treatment, will be critical.
Our findings point to the need for more research on the scope and magnitude of ARV diversion, with a particular focus on how the rollout of treatment as prevention and PrEP impact illicit markets for these medications. Moreover, it is important that clinicians be aware of ARV street markets, and the potential for such markets to result in patients’ low adherence and increased risk for health problems, ARV resistance, and onward disease transmission. At the same time, care must be taken not to restrict patients’ supplies such that office visits are too frequent to be manageable, or that patients are at risk for non-adherence because of running out of medication. Most importantly, ARV diversion - and related risks of treatment failure, resistance, disease transmission, and PrEP failure – should be considered in developing policy and behavioral supports to scaling up treatment as prevention and PrEP.
Acknowledgments
This research was supported by DHHS Grant Number 5 R01 DA024579 from the National Institute on Drug Abuse. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute on Drug Abuse or the National Institutes of Health.
References
- Associated Press. AIDS drugs surface on black market. New York Times. 1995 Dec 25;:43. [Google Scholar]
- Bangsberg DR, Perry S, Charlebois ED, Clark RA, Robertson M, Zolopa AR. Non-adherence to highly active antiretroviral therapy predicts progression to AIDS. AIDS. 2001;15(9):1181–1183. doi: 10.1097/00002030-200106150-00015. [DOI] [PubMed] [Google Scholar]
- Centers for Disease Control and Prevention. Interim guidance for clinicians considering the use of pre-exposure prophylaxis for the prevention of HIV infection in heterosexually active adults. Morbidity and Mortality Weekly Report. 2012;61:586–589. [PubMed] [Google Scholar]
- Curran JW, Crosby RA. Pre-exposure prophylaxis for HIV: Who will benefit and what are the challenges? American Journal of Preventive Medicine. 2013;44(1S2):S163–S166. doi: 10.1016/j.amepre.2012.10.005. [DOI] [PubMed] [Google Scholar]
- Dennis ML, Titus JC, White MK, Unsicker JI, Hodgkins D. Global Appraisal of Individual Needs - Initial (GAIN-I) Bloomington, IL: Chestnut Health Systems; 2002. [Google Scholar]
- Dorschner J. Activists: HIV care scam uses homeless. Miami Herald. 2005 Jun 30;:1A. [Google Scholar]
- Flaherty MP, Gaul GM. Florida Medicaid fraud costs millions, report says. Washington Post. 2003 Dec 19;:E03. [Google Scholar]
- Food and Drug Administration. Truvada for PrEP fact sheet: Ensuring safe and proper use. 2012 Retrieved from http://www.fda.gov/downloads/newsevents/newsroom/factsheets/ucm312279.pdf.
- Glasgow K. The new dealers: They’re poor, black, and HIV-positive. Their product? The AIDS medications intended to cure them. Miami New Times 1999 Oct 21; [Google Scholar]
- Grelotti DJ, Closson EF, Mimiaga MJ. Pretreatment antiretroviral exposure from recreational use. The Lancet Infectious Diseases. 2013;13(1):10–12. doi: 10.1016/S1473-3099(12)70294-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hurt CB, Eron JJ, Cohen MS. Pre-exposure prophylaxis and antiretroviral resistance: HIV prevention at a cost? Clinical Infectious Diseases. 2011;53(12):1265–1270. doi: 10.1093/cid/cir684. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Inciardi JA, Surratt HL, Kurtz SP, Burke JJ. The diversion of prescription drugs by health care workers in Cincinnati, Ohio. Substance Use and Misuse. 2006;41(2):255–264. doi: 10.1080/10826080500391829. [DOI] [PubMed] [Google Scholar]
- Inciardi JA, Surratt HL, Kurtz SP, Cicero TJ. Mechanisms of prescription drug diversion among drug-involved club and street-based populations. Pain Medicine. 2007;8(2):171–183. doi: 10.1111/j.1526-4637.2006.00255.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Juusola JL, Brandeau ML, Owens DK, Bendavid E. The cost-effectiveness of preexposure prophylaxis for HIV prevention in the United States in men who have sex with men. Annals of Internal Medicine. 2012;156:541–550. doi: 10.1059/0003-4819-156-8-201204170-00001. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kippax S. Effective HIV prevention: The indispensable role of social science. Journal of the International AIDS Society. 2012;15(2):17357. doi: 10.7448/IAS.15.2.17357. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Koenig LJ, Lyles C, Smith DK. Adherence to antiretroviral medications for HIV pre-exposure prophylaxis: Lessons learned from trials and treatment studies. American Journal of Preventive Medicine. 2013;44(IS2):S91–S98. doi: 10.1016/j.amepre.2012.09.047. [DOI] [PubMed] [Google Scholar]
- Krakower DS, Mimiaga ML, Rosenberger JG, Novak DS, Mitty JA, White JM, et al. Limited awareness and low immediate uptake of pre-exposure prophylaxis among men who have sex with men using an internet social networking site. PLoS ONE. 2012;7(3):e33119. doi: 10.1371/journal.pone.0033119. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Liu AY, Kittredge PV, Vittinghoff E, Raymond HF, Ahrens K, Matheson T. Limited knowledge and use of HIV post- and pre-exposure prophylaxis among gay and bisexual men. Journal of Acquired Immune Deficiency Syndrome. 2008;47(2):241–247. [PubMed] [Google Scholar]
- Mansergh G, Koblin BA, Colfax GN, McKirnan DJ, Flores SA, Hudson SM. Preefficacy use and sharing of antiretroviral medications to prevent sexually-transmitted HIV infection among us men who have sex with men. Journal of Acquired Immune Deficiency Syndrome. 2010;55(2):e14–e15. doi: 10.1097/QAI.0b013e3181f27616. [DOI] [PubMed] [Google Scholar]
- Mimiaga MJ, Case P, Johnson CV, Safren SA, Mayer KH. Preexposure antiretroviral prophylaxis attitudes in high-risk boston area men who report having sex with men: Limited knowledge and experience but potential for increased utilization after education. Journal of Acquired Immune Deficiency Syndrome. 2009;50(1):77–83. doi: 10.1097/QAI.0b013e31818d5a27. [DOI] [PMC free article] [PubMed] [Google Scholar]
- O’Grady C, Surratt HL, Kurtz SP. Antiretroviral Medication Diversion in South Florida: Prescription Types and Motivations. Poster presented at the 75th Annual Meeting of The College on Problems of Drug Dependence; San Diego, California. 2013. Jun 15, [Google Scholar]
- Philpott S. Social Justice, Public Health Ethics, and the Use of HIV Pre-Exposure Prophylaxis. American Journal of Preventive Medicine. 2013;44(IS2):S137–S140. doi: 10.1016/j.amepre.2012.09.029. [DOI] [PubMed] [Google Scholar]
- Smith D, Grant R, Weidle P, Lansky A, Mermin J, Fenton K. Interim guidance: Preexposure prophylaxis for the prevention of HIV infection in men who have sex with men. MMWR Morbidity and Mortality Weekly Report. 2011;60(3):65–68. [PubMed] [Google Scholar]
- Surratt HL, Kurtz SP. Paper presented at the Nova Southeastern University Facutly Symposium. Nova Southeastern University; 2013. A national perspective on the abuse and diversion of prescription drugs. Retrieved from http://arsh.nova.edu/presentations/forms/a_national_perspective_on_the_abuse_and_diversion_of_prescription_drugs.pdf. [Google Scholar]
- Surratt HL, Kurtz SP, Cicero TJ, O’Grady C, Levi-Minzi MA. Antiretroviral medication diversion among HIV-positive substance abusers in South Florida. American Journal of Public Health. 2013;103(6):1026–1028. doi: 10.2105/AJPH.2012.301092. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weber J, Tatoud R, Fidler S. Postexposure prophylaxis, preexposure prophylaxis or universal test and treat: The strategic use of antiretroviral drugs to prevent HIV acquisition and transmission. AIDS. 2010;24(suppl 4):S27–S39. doi: 10.1097/01.aids.0000390705.73759.2c. [DOI] [PubMed] [Google Scholar]