Our greatest weakness as a community of AIDS physicians is that we have approached our "own" epidemic with great naiveté, when we might have looked to our colleagues in tuberculosis (TB) and sexually transmitted disease (STD) clinics for tools and advice.

For example, it took us years to find out that combination therapy was the right thing to do for a highly mutable pathogen. TB physicians learned this difficult lesson more than 4 decades ago. We also were unable to see the long reach of AIDS into marginalized communities for many years -- until Paul Farmer^[1] and Jonathan Mann^[2] forced us to open our eyes. We have only recently implemented partner notification, a system long employed by STD clinics to arrest the spread of STDs in the community. And we have continued, with great optimism, to hand our patients piles of pills to take on a daily basis for the rest of their lives, ignoring lessons already learned in the context of multidrug-resistant (MDR) TB. Directly observed therapy (DOT) was the answer to the problem of MDR TB in the early 1990s. Clarke and colleagues^[3] provide proof that this ancient tool of the TB trade can also be adapted to the management of HIV infection in patients who are in recovery from substance abuse. Appropriate implementation of DOT in selected patients may delay the emergence of MDR HIV in the future.

TB and HIV infection are similar in many ways. HIV infection, like TB, is a chronic and contagious infection that predominantly affects marginalized communities, members of which have been traditionally difficult to engage in long-term care and may have coinfections (such as hepatitis C virus [HCV] infection) that complicate the management of their illness. HIV, like Mycobacterium tuberculosis, will mutate to resistant forms if multidrug therapy is not given on a daily basis. HIV infection, like TB, is managed using drugs that have many unpleasant side effects and that may be associated with serious medical complications. HIV infection, like TB, is a public health crisis that demands leadership and vision. One need not look much further than the extensive literature on DOT for TB to learn how necessary and successful DOT has been for the management of that disease.^[4]

HIV providers who wish to initiate DOT have much to learn from DOT expert John A. Sbarbaro, who is one of the most colorful and outspoken characters in the TB field. Would that we had listened to him at the beginning of our epidemic. In 1985, Sbarbaro^[5] wrote:

The failure of patients to comply with their therapeutic regimen has an extensive impact on the costs and strategies of medical care. Compliance with long-term regimens can be improved by linking the timing of the medication to existing daily habits, reducing the number of times that a medication is to be taken each day, and identifying the side effects that a patient attributes to the treatment. . . . The establishment of a strong patient/physician relationship is central to long-term therapeutic success.

It is amazing that we have had to rediscover these truths as they relate to HIV. Recently, Sbarbaro and colleagues^[6] have shown, in a study of TB patients performed in an urban setting, that substance (alcohol) abuse and homelessness were predictive of failure of DOT. Similar problems with DOT for management of HIV disease have been observed as well.^[7]

Several important caveats about DOT for HIV infection bear reinforcement. First, simplification of HAART regimens will be critical to the success of this approach. Recent clinical information on once-daily dosing regimens and combination therapy will facilitate the adaptation of HAART to DOT.^[8] Some of these regimens were implemented by Clarke and associates in their study. One new drug that was not available to the authors at the time is tenofovir, a potent nucleotide reverse transcriptase inhibitor that is given once daily. Fixed-dose combination formulations are also simplifying regimens, although the US pharmaceutical industry has failed, thus far, to combine drugs made by several different pharmaceutical companies. It may be high time for the industry to set intercompany "competition" aside so that we can have fixed-dose combinations that will work for DOT. One obvious cross-company combination that would be useful would be stavudine-tenofovir-efavirenz.

A second concern mentioned by the authors is that HCV infection complicated the management of HIV infection in their patient population. Thus, it may be important to consider treating HCV infection before treating HIV infection in selected patients.^[9] Treatment of HCV infection also lends itself to DOT, although treatment of active substance abusers or recently recovered persons is still very controversial because of their chance of reinfection.

A third concern for physicians wishing to implement DOT is interaction with methadone therapy. Many antiretroviral drugs decrease the blood level of methadone, while others increase it. The authors review these interactions here and have also reviewed the subject in greater detail elsewhere.^[10] Another concern, not addressed by the authors, might be what happens after methadone treatment -- for those patients who choose to terminate methadone -- and what to do about patients who relapse. Should DOT be tapered in preparation for therapeutic independence, as methadone treatment is tapered?

Furthermore, it is clear that DOT for TB delivers more than just medication. Patients are able to access TB treatment and expert advice on their care at specialty centers at little or no cost to themselves. Should we not also plan to set up specialty treatment centers for AIDS, where patients who would not normally have access to care can be given treatment, regardless of their substance abuse status? Peering into the future, it seems likely to this writer that we will need to learn how to provide DOT to all persons who might benefit, regardless of their current position in the continuum of substance use. Thus, more studies on the interactions between HAART and crack cocaine and heroin, and in communities of persons in recovery from substance abuse, are desperately needed.

Another final concern that was not addressed by the authors is who will pay for DOT? Again, we need to draw on past lessons and look to the future: AIDS is a public health problem of global dimensions. DOT is just one small part of a much larger picture. We need to put clinical systems in place that will engage the estimated 200,000 HIV-infected Americans who have yet to be identified,^[11] many of whom are likely to be members of substance-abusing communities. We need to enable these persons to access care; devise drug treatment regimens that they can adhere to; and address the many other issues in their lives, such as homelessness and substance abuse, that may affect their willingness and ability to adhere to treatment. To put these systems in place, we need leadership at the highest levels of government. We also need to reach out to our TB colleagues in this country and in the developing world to combine forces.

Making DOT part of our approach to HIV management for patients in recovery from substance abuse is a small step forward in the new history of HIV. How long will it take us to learn the next obvious lesson from our TB colleagues -- that everyone in the global community who is affected by HIV must be treated if we hope to see a future without AIDS?

Anne S. De Groot, MD
Assistant Professor of Community Health and Medicine
Brown University School of Medicine
Providence, RI

References

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2. Mann J, Wilson ME. AIDS: global lessons from a global epidemic. BMJ. 1993;307:1574-1575.
3. Clarke S, Keenan E, Ryan M, et al. Directly observed antiretroviral therapy for injection drug users with HIV infection. AIDS Reader. 2002;12:305-316.
4. Sbarbaro JA. Tuberculosis in the 1990s: epidemiology and therapeutic challenge. Chest. 1995;108(2 suppl):58S-62S. Available at: http://www.chestjournal.org/cgi/reprint/108/2/58S.
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11. Fleming PL, Byers RH, Sweeney D, et al. HIV prevalence in the United States, 2000. In: Program and abstracts of the 9th Annual Retrovirus Conference; February 24-28, 2002; Seattle. Abstract 11.