JAIDS Journal of Acquired Immune Deficiency Syndromes:
Is It Time for Treatment as Prevention Among People Who Inject Drugs?
Bruce, R. Douglas MD, MA, MSc
Yale University AIDS Program, New Haven, CT
The author has no funding or conflicts of interest to disclose.
Approximately 5% of the global population, or 230 million people have used drugs.1 An estimated 15.9 million individuals in 148 countries inject various drugs of abuse; 3 million of these are estimated to be HIV infected.2 Although injection drug use only impacts 0.34% of the global population, it represents approximately 10% of the global HIV epidemic! This disparity is due to the frequency with which individuals inject themselves and the efficiency with which injection transmits HIV. This link between drug injection and HIV has been well described since the beginning of the HIV pandemic.3 With this understanding, global efforts were (and are being) mobilized to address this through key HIV prevention interventions, including needle and syringe programs4 and medication-assisted treatment (e.g., buprenorphine and methadone).5
Initially, drug users were not provided with antiretroviral therapy (ART) at a similar frequency as other key populations such as men who have sex with men.6 This was the result of fears regarding nonadherence and the development of resistance.7 Although the 1990's were home to complex regimens with notable side-effect profiles (eg, full dose ritonavir) that were difficult for anyone to take, nonadherence seemed focused on people who inject drugs (PWID).8 Although such information resulted in the deferral of treatment for many drug users, it motivated some to develop interventions to improve adherence to ART among drug users who struggle with adherence.9,10 Others challenged the assumption of nonadherence and examined larger data sets to reveal that resistance was as common among PWID as those who do not.11 Today, ART has revolutionized the clinical course of HIV12–14 and HIV Prevention Trials Network 052 demonstrated that ART is both treatment for the infected person and effective HIV prevention for the uninfected sexual partner in serodiscordant couples.15 The data are so convincing that the HIV-infected partner in a serodiscordant couple should be offered treatment irrespective of CD4 count to reduce the risk of HIV transmission. Naturally, individuals speculate on the application of these results to other risk groups, such as injection risk. And, assuming similar efficacy among PWID, it would be time to ask, “Should PWID be considered a special population to provide immediate access to ART?” Gupta et al16 recently reviewed ART guidelines in 70 countries and found that none of the countries viewed PWID as requiring any special level of ART attention. Only 4 countries even mention ART for PWID (Guyana, Myanmar, Russia, and Vietnam), and all 4 apply the same criteria to start ART as for the general population, suggesting that thoughts on 052's application to PWID has not been considered in policy measures to date. Of critical importance is the realization that statements and their actual operationalization are not always concordant, as is evidenced by the obstacles in Russia for PWID that prevent access to HIV therapy despite officially qualifying for treatment.17
And this brief history sets the stage for the article by Kato et al in this issue of JAIDS that raises critical questions regarding the appropriate allocation of resources among key populations toward addressing the overall HIV epidemic. Kato M, Granich R, Duc Bui D, Tran HV, Nadol P, Jacka D, Sabin K, Suthar AB, Mesquita F, Lo YR, Williams B. The potential impact of expanding antiretroviral therapy and combination prevention in Vietnam: Towards elimination of HIV transmission. J Acquir Immune Defic Syndr 2013. Kato et al used mathematical modeling to gauge the impact of various strategies for HIV prevention on the largely PWID-driven HIV epidemic in the Can Tho province of Vietnam. The strategies examined include periodic HIV testing with immediate ART, targeting of specific populations, and the use of combined strategies, such as methadone and condom use. Their modeling argues that annual testing of key populations, such as PWID, with immediate access to ART, although expensive initially, is an investment with a substantial payoff in the future. That is, annual testing finds more patients than current testing models; therefore, more people start HIV therapy earlier (the cost). With more people starting HIV therapy, there is a reduction in the overall community viral load among PWID, thereby reducing HIV infection among that group (the payoff). Although not explored in the modeling, an additional benefit to early access to ART is reduction in morbidity and mortality and the resultant overall cost savings of ART in treated population. Understanding the high prevalence of hepatitis C virus among PWID, for example, immediate ART may help slow the progression of liver fibrosis among PWID infected with HIV/hepatitis C virus, further reducing morbidity and increasing cost savings.
The injection of drugs is related to HIV much like gasoline to fire—it takes a serious issue and logarithmically makes it worse. HIV in a PWID community is much like a fire engulfing an entire apartment complex. HIV treatment, following the metaphor, is much like firefighting. In such a situation, one marshals additional resources to meet the need—it is more complex and requires more extensive equipment than a house fire. Current HIV prevention strategies for PWID have marshaled some of the fire department (namely needle and syringe programs and methadone for those who use opioids) but have failed to bring the entire fire department to the rescue. As a result, the fire continues and spills over into other communities that do not inject drugs.
The proposition of testing all PWID for HIV and then immediately starting them on ART irrespective of CD4 count is sure to bristle many. These individuals will have several concerns that we must seriously consider. As with all infectious diseases, infection with HIV is dose dependent; the probability of HIV infection increases as the infective dose increases. The first concern then is, how much reduction in the risk of infection does a reduction in HIV viral load produce when injecting drugs contaminated with blood? Although this has not been formally quantified, it is logical to presume a reduction in HIV viral load would provide some degree of protection. Understanding that the quantitative efficacy is not known, the authors ran several models, varying the assumed efficacy downward to 70% and found that such reductions attenuate the efficacy but do not eliminate it. At 70% efficacy, Kato et al found an estimated 54% of cumulative new infections could be prevented with combination prevention scale-up with periodic HIV testing and immediate access to ART.
Second, there is the concern that the allocation of funds toward treatment will result in fewer funds for harm reduction. To deny ART to fund harm reduction measures is faulty logic and pits treatment and prevention against each other. We would not, in the treatment of diabetes, for example, argue to stop funding diabetes treatment to invest those funds in obesity prevention so as to reduce the incidence of diabetes. In a world with effective HIV therapy, the right to health is operative and all drug users, including PWID, should have access to life-saving treatment. Nations will need to prioritize their allocations based on budgetary constraints. Every nation, however, must bear in mind the clear benefits of ART among PWID, the overall cost benefit modeled by Kato et al, and the clear right to health that all people have irrespective of their use of drugs.
Third, some may ask if drug users should be a priority population given they placed themselves at risk. Although asked in darker corners of policy meetings, it must be brought into the open. Of course, the majority of people in the world with HIV placed themselves at risk of HIV and we continue to offer them ART. Why should drug use be any different? The allocation of resources should not be based on any moralizing regarding the behaviors that may have resulted in the acquisition of HIV. The allocations of resources must be calculated toward what investment can reap the greatest benefit toward preventing other HIV infection and reducing morbidity and mortality from HIV. Although the World Health Organization has not provided clear guidance on this issue relative to PWID,16 the study by Kato et al, and a growing body of literature on this topic,18 argues that PWID, as a driver of the HIV epidemic in many locations, should be a priority population to address HIV through combination prevention strategies and immediate access to HIV treatment irrespective of CD4 count.
Fourth, some will agree with the focus on PWID but will be concerned about state involvement in such interventions where such testing and treatment is punitive rather than voluntary and humane. The fear of unintended negative consequences to the few cannot drive policy that can save the many. Gay men, for example, did not argue to postpone HIV testing and treatment until all gay men were free from stigma and punishment from society. Rather they faced such issues with courage and used such issues as a platform to decry the system and advocate for change. Where such punitive systems arise for drug users, it is the job of advocacy to correct.
The final objection I fear will be the age-old fear that drug users will not be adherent to ART and so there is no need to even consider immediate treatment. As previously discussed above, PWID can be adherent to treatment.11 A recent paper by Choopanya et al. demonstrated that PWID were able to adhere to enough tenofovir disoproxil fumarate to reduce their risk of HIV by 48.9%.19 Clearly PWID are capable of taking medications. For individuals who struggle with adherence, interventions have been and can be created to provide sufficient support to help even the most difficult patient succeed in treatment if such support is needed.5,10 The fear of nonadherence is not a justification to deny treatment. Knowing that treatment is effective, it is the responsibility of healthcare systems to provide treatment in a manner in which those in need may benefit—that is the true implication of a right to health.
Kato et al have provided an important mathematical model with data that must be considered seriously. The time has come to set aside the stigma of injection and to appropriately allocate resources to address HIV among PWID, which includes needle and syringe programs, medication-assisted treatment (eg, methadone), HIV testing, and, now, immediate access to ART.
1. UNODC, World Drug report 2012 (United Nations publication, Sales No. E.12.XI.1). Malta, June 2012.
2. Nelson PK, Mathers BM, Cowie B, et al.. Global epidemiology of hepatitis B and hepatitis C in people who inject drugs: results of systematic reviews. Lancet. 2011;378:571–583.
3. Hart GJ, Sonnex C, Petherick A, et al.. Risk behaviours for HIV infection among injecting drug users attending a drug dependency clinic. BMJ. 1989;298:1081–1083.
4. Wodak A, Maher L. The effectiveness of harm reduction in preventing HIV among injecting drug users. New South Wales Public Health Bulletin. 2010;21:69–73.
5. Altice FL, Bruce RD, Lucas GM, et al.. HIV treatment outcomes among HIV-infected, opioid-dependent patients receiving buprenorphine/naloxone treatment within HIV clinical care settings: results from a multisite study. J Acquir Immune Defic Syndr. 2011;56(suppl 1):S22–S32.
6. van Asten LC, Boufassa F, Schiffer V, et al.. Limited effect of highly active antiretroviral therapy among HIV-positive injecting drug users on the population level. Eur J Public Health. 2003;13:347–349.
7. Palepu A, Yip B, Miller C, et al.. Factors associated with the response to antiretroviral therapy among HIV-infected patients with and without a history of injection drug use. AIDS. 2001;15:423–424.
8. Lucas GM, Chaisson RE, Moore RD. Highly active antiretroviral therapy in a large urban clinic: risk factors for virologic failure and adverse drug reactions. Ann Intern Med. 1999;131:81–87.
9. Altice FL, Maru DS, Bruce RD, et al.. Superiority of directly administered antiretroviral therapy over self-administered therapy among HIV-infected drug users: a prospective, randomized, controlled trial. Clin Infect Dis. 2007;45:770–778.
10. Berg KM, Litwin A, Li X, et al.. Directly observed antiretroviral therapy improves adherence and viral load in drug users attending methadone maintenance clinics: a randomized controlled trial. Drug Alcohol Depend. 2011;113:192–199.
11. Wood E, Hogg RS, Yip B, et al.. Rates of antiretroviral resistance among HIV-infected patients with and without a history of injection drug use. AIDS. 2005;19:1189–1195.
12. Altice FL, Kamarulzaman A, Soriano VV, et al.. Treatment of medical, psychiatric, and substance-use comorbidities in people infected with HIV who use drugs. Lancet. 2010;376:367–387.
13. Friedland G, Vlahov D. Integration of buprenorphine for substance-abuse treatment by HIV care providers. J Acquir Immune Defic Syndr. 2011;56(suppl 1):S1–S2.
14. Bruce RD, Eiserman J, Acosta A, Gote C, Lim JK, Altice FL. Developing a modified directly observed therapy intervention for hepatitis C treatment in a methadone maintenance program: implications for program replication. The American journal of drug and alcohol abuse 2012;38: 206–212.
15. Cohen MS, Chen YQ, McCauley M, et al.. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011;365:493–505.
16. Gupta S, Granich R, Suthar AB, et al.. Global Policy Review of ART Eligibility Criteria for treatment and prevention of HIV and TB in adults, pregnant women, and serodiscordant couples: ART recommendations by national guidelines. J Acquir Immune Defic Syndr. 2013;62:e87–e97.
17. Sarang A, Rhodes T, Sheon N. Systemic barriers accessing HIV treatment among people who inject drugs in Russia: a qualitative study. Health Policy Plan. 2013; In press.
18. Bruce RD. Methadone as HIV prevention: high volume methadone sites to decrease HIV incidence rates in resource limited settings. Int J Drug Policy. 2010;21:122–124.
19. Choopanya K, Martin M, Suntharasamai P, et al.. Antiretroviral prophylaxis for HIV infection in injecting drug users in Bangkok, Thailand (the Bangkok Tenofovir Study): a randomized, double-blind, placebo-controlled phase 3 trial. Lancet. 2013;381:2083–2090.
© 2013 by Lippincott Williams & Wilkins
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