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Care of Injection Drug Users with HIV
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Introduction
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Treatment for Substance Use Disorders
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transparent imageSelf-Help Programs
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transparent imageResidential Treatment Programs for Substance Use Disorders
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transparent imageMedical Treatments for Substance Use Disorders
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transparent imageMethadone Treatment of Opiate Dependence
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transparent imageOther Medical Treatments for Injection Opiate Use
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Integrating Substance Abuse and HIV Care
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transparent imageThe Example of Methadone Treatment Programs
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transparent imageAdherence To HIV Medications
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transparent imageCounseling
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Ancillary Services Provided Through Drug Abuse Treatment Settings
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Stimulant Use
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transparent imageCocaine Use
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transparent imageAmphetamines
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transparent imageMedical Treatments for Stimulant Abuse
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HIV Medical Care in Drug Users: Behavioral Aspects
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HIV Medical Care Settings for Drug Users
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References
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Related Resources
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Introduction
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This chapter reviews approaches to the care of HIV-infected drug users. Injection drug users (IDUs) are a growing group of patients with HIV disease. Injection drug use is an important HIV transmission route, particularly affecting minorities, women, and children. Providing drug abuse treatment to HIV-infected individuals is crucial because it can prevent HIV transmission by reducing needle use and needle sharing.(1,2) In addition to reducing needle sharing, drug abuse treatment has the potential to prevent HIV transmission by reducing the number of impulsive and possibly unsafe sex acts associated with the intoxication and disinhibition that results from drug use. Drug abuse treatment can also provide a setting to deliver other services needed by HIV-infected patients, including HIV medical care, psychiatric treatment, social services, and education about HIV disease. Furthermore, drug abuse treatment may be helpful in reducing the morbidity associated with HIV infection(3) and may have the potential to reduce utilization of medical services by HIV-infected drug users.

This chapter reviews some of the major types of treatment approaches for substance use disorders, their relevance to the care of HIV-infected drug users--focusing on the treatment of opiate and stimulant users--and briefly describes various models for integrating the treatments for HIV disease and substance abuse.

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Treatment for Substance Use Disorders
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In order to provide adequate treatment for HIV-infected patients with substance use disorders, health care providers must first assess the presence and severity of substance use. Substance use will be common among many HIV clinic populations, although prevalence and drug choice will vary widely by region. In general opiates and stimulants are the most common drugs of abuse, and have the most impact on HIV transmission. Although alcohol and tobacco use are also important sources of additional morbidity in the HIV-infected patient, due to space limitations these drugs will not be addressed in this chapter. Once drug use is established, referral can be made to specialized treatment for substance use disorders.

Drug abuse intervention approaches can be broadly grouped into three types: self-help, psychosocial treatments, and medical treatments. Treatment settings are usually outpatient, but can be residential.(4) Treatment of HIV-infected patients in any of these modes presents a number of opportunities as well as problems and requires novel strategies.

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Self-Help Programs
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Self-help groups, while not treatment as such, probably offer the most widely accessible form of assistance to patients with substance use disorders. They are free and available in virtually all metropolitan areas. The most common types of self-help programs are the so-called Twelve Step groups, such as Alcoholics Anonymous (AA) and Narcotics Anonymous (NA). NA is particularly relevant to HIV-infected drug users because many participants are IDUs or former IDUs. These groups are extremely valuable in offering support for sobriety and abstinence. Twelve Step programs have a strong abstinence orientation and a philosophy that emphasizes medication-free treatment. While they are very helpful to motivated drug users, the Twelve Step programs may not be able to offer interventions intensive or potent enough to stop or reduce needle use among many IDUs. Specialized Twelve Step groups for HIV-infected drug users may be particularly helpful, and may be available in large metropolitan areas where HIV prevalence among drug users is high.

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Residential Treatment Programs for Substance Use Disorders
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Residential programs are usually based on the therapeutic community model. These programs offer treatment in a long-term residential setting, usually lasting 6 to 18 months. Therapeutic communities provide an intensive peer milieu designed to produce behavioral changes in the drug user. Principles of treatment include the use of peer support, confrontation, and behavior shaping, which uses milieu-based rewards and punishments. Relatively few IDUs are motivated enough to voluntarily seek entry to these long-term and demanding programs, although many enter because of legal coercion. Of those who enter treatment, only a minority stay until completion. However, for those IDUs who do stay in treatment, residential therapeutic communities offer a powerful tool for change.

Residential programs have in recent years begun to address the special problems of treating HIV-infected clients.(5) Patients with HIV disease, especially if their symptoms are advanced, may be reluctant to commit themselves to very long periods of residential substance abuse treatment. Residential programs have recently responded by lowering the threshold to admission and employing greater flexibility in dealing with HIV-infected clients-- for example, by shortening the duration of residential treatment.

Residential programs that attempt to work with HIV-infected clients must also come to terms with the medical aspects of HIV disease. Such programs are usually not set up to provide the medical monitoring, evaluation, and treatment sick residents require. Related problems include the question of when to move residents from a therapeutic community to a hospital or hospice and, more generally, to what degree the needs of the residential treatment community should be subordinated to the medical needs of the individual resident.

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Medical Treatments for Substance Use Disorders
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Medical treatments for drug abuse employ a medical model involving physicians and other health-care professionals and frequently use medication. Pharmacologic approaches are usually specific for each class of drugs--for example, benzodiazepines for alcohol withdrawal, disulfiram or naltrexone for alcohol dependence, clonidine or methadone for opiate detoxification, and naltrexone or methadone for maintenance treatment of opiate dependence.

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Methadone Treatment of Opiate Dependence
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Significant numbers of IDUs in the United States are primary opiate users whose drug of choice is generally heroin. While nonmedical treatments such as self-help programs and residential therapeutic communities play important roles, by far the most common form of treatment is methadone maintenance treatment. Methadone maintenance focuses on the pharmacotherapy of chronic opiate dependence by utilizing daily observed oral dosing with methadone hydrochloride combined with outpatient individual and/or group counseling. Methadone is usually given in single doses ranging from 60 to 100 mg per day. The usually effective dose is at or above 60 mg per day. Methadone dosing may be affected by interactions with other medications used in HIV disease. Methadone is extensively metabolized by cytochrome P450 3A4, and the methadone level may decrease when methadone is used together with P450 3A4 inducers such as carbamazepine and rifampin -- necessitating higher doses. Conversely, methadone levels could be raised by P450 3A4 inhibitors such as the protease inhibitor ritonavir.(6) In turn, methadone inhibits the metabolism of zidovudine (AZT) and can elevate AZT levels.(7)

It is essential to note that additional analgesics are needed to treat acute or chronic pain in the HIV-infected drug user who is on methadone maintenance treatment, because patients do not obtain adequate pain relief from their usual daily dose of methadone, to which they have become tolerant.

Methadone treatment is generally associated with improved health status in heroin users. In addition, the methadone treatment setting is useful for providing medical services, such as tuberculosis prevention, to patients with HIV disease. Furthermore, methadone treatment may have the potential to reduce utilization of medical services by HIV-infected drug users.(8)

More than 100,000 patients currently receive methadone treatment in the United States.(9) Of these, about 80,000 are in methadone maintenance programs. Most of the rest are in 21-day methadone detoxification programs. Methadone detoxification consists of progressive, gradual, daily tapering of methadone over a 21-day period, generally on an outpatient basis. A small number of patients receive methadone during inpatient hospitalization, and a few others are in longer detoxification programs lasting up to 180 days. Methadone maintenance treatment is often used as a last resort for patients who have failed other treatments or who cannot or will not enter other forms of treatment. Methadone treatment is generally highly effective in reducing injection opiate use and its associated criminality.(1) However, methadone detoxification is probably inappropriate for HIV-infected patients because the 21-day course of detoxification is rarely successful in stopping injection drug use even in "healthy" IDUs and probably has less chance of success among more highly stressed patients with HIV infection.

Methadone maintenance treatment programs offer a number of benefits including a long-term, stable treatment setting and a variety of other medical, psychiatric, and social services.(10) HIV medical care may be more effective if it is situated on site in methadone treatment programs.(11-13) The demonstrated effectiveness of methadone maintenance treatment in reducing injection drug use along with its utility as a medical service delivery platform give it a special role in the treatment of IDUs at risk for HIV disease.

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Other Medical Treatments for Injection Opiate Use
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Other medical treatments for heroin addiction include clonidine, naltrexone, and levo-alpha-acetyl methadol (LAAM). Clonidine is useful as a nonaddictive agent to counteract acute opiate withdrawal symptoms but has little, if any, role in long-term treatment of HIV-infected IDUs. Naltrexone, a long-acting oral opioid antagonist, is useful only in patients sufficiently motivated to comply with its use and take medication regularly. Unfortunately, relatively few injection heroin users appear willing to try naltrexone. Some IDUs are reluctant to take naltrexone as it has no perceptible psychoactivity and because they fear the possibility of opiate withdrawal symptoms during initiation of treatment.

LAAM may be a useful alternate to methadone for the treatment of opioid dependence, because its longer half-life requires only thrice weekly rather than daily attendance.

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Integrating Substance Abuse and HIV Care
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The Example of Methadone Treatment Programs
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The Opiate Treatment Outpatient Program (OTOP) is a specialized outpatient substance abuse treatment program at San Francisco General Hospital (SFGH) for patients with HIV disease. OTOP provides combined treatment for HIV drug abuse and other chronic medical and psychiatric problems for more than 150 HIV-infected IDUs. Patients attending the program are a heterogeneous group, although minorities (chiefly African-American and Latino) are overrepresented. Nearly 40% are women, 15% are homosexual, bisexual, or transgender, and some are the parents of HIV-infected children. HIV-infected IDUs are preferentially admitted to OTOP methadone treatment services in an attempt to remove IDUs from the pool of needle users and possible needle sharers.

Methadone treatment of HIV-infected injection opiate users requires a number of changes from usual treatment approaches. Greater flexibility and tolerance of slower or incomplete treatment response is needed in the substance abuse care of HIV-infected patients, who generally have more severe psychosocial problems than other drug users.(14) Psychological distress is high and manifests itself particularly as depression and suicidal thoughts. In a study of HIV-infected methadone maintenance treatment patients, 79% were found to have current DSM-III-R Axis I psychiatric disorders. Nearly two thirds of these individuals had two or more current Axis I disorders.(14) Although this high rate of current psychiatric disorders is similar to rates found among in-treatment opioid-dependent patients in studies done prior to the AIDS epidemic, it is much higher than the rates documented among HIV-infected homosexual and bisexual men.(15) This high level of psychological distress can make substance abuse treatment more difficult. HIV-infected substance-abusing patients may therefore need more time than other drug abusers to recover from their drug use.

Methadone treatment programs have traditionally encouraged patients to taper off methadone and eventually live abstinent or "drug-free" lives. Unfortunately, discontinuing methadone treatment for extended periods is rarely successful; more than 80 percent of addicts resume drug use within 1 year after stopping methadone treatment.(1) For HIV-infected patients, the health risks of discontinuing methadone treatment and returning to injection drug use may be too high. There are public health costs also, because HIV-infected patients who resume using injection drugs may return to other high-risk behaviors that spread HIV, such as unsafe sex and needle sharing.

Finally, although all substance abuse treatment requires some forms of limit setting to address unacceptable behavior, the behavioral problems of HIV-infected IDUs may require greater than usual tolerance. It is important to find ways to avoid terminating a patient's treatment. The OTOP clinic attempts to intensify treatment through providing extra counseling sessions rather than discharge patients whose continued drug use might have led to termination of treatment from traditional treatment programs for substance use. Unfortunately, even HIV-infected patients may need to be discharged if their continued treatment is judged harmful to the program--for example, in cases of violent behavior.

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Adherence To HIV Medications
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State-of-the-art treatment of HIV offers substantial health benefits. However, the current pharmacotherapeutic arsenal includes an increasing number of antiretroviral agents and other treatments. Consequently, medical treatment for HIV disease may include a wide range of prescriptions that require patients to take medications several times a day on a complex schedule. For medications to be effective, patients need to adhere to their prescribed treatment regimens. Current understanding of HIV pathogenesis indicates that missing even one or a few doses of antiretroviral medication may have severe detrimental effects because resulting decreased medication blood levels allow rapid selection of drug-resistant HIV strains. Concern with enhancing treatment for HIV disease has prompted investigators to develop interventions to augment adherence.(16)

Some research shows that drug injectors have poorer adherence to medications for HIV disease than other groups(17,18) and that patients frequently skip taking their medicine because of alcohol ingestion or drug use. Others have found that IDUs may be less willing to begin zidovudine (ZDV) therapy, but they can adhere just as well to ZDV regimens as AIDS patients in other risk groups.(19) In the OTOP methadone maintenance program at San SFGH described above, adherence to medications has been a problem for about half the patients with HIV disease.(20) Two techniques to improve medication adherence have been applied for patients in the methadone maintenance program at SFGH. The first technique provided on-site dispensing of antiretroviral ZDV, the main treatment for HIV disease at the time this study was performed in 1993-1994. On-site dispensing enhanced medication adherence, but its effects did not endure.(20) Second, to develop a more long-lasting intervention, the program is experimenting with more individualized medication management,(21) in which a staff member provides assessment and problem-solving to help improve medication adherence. Both techniques encourage patients to be pro-active in managing their treatment regime and overall health care.

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Counseling
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Counseling specific to HIV disease is a necessary part of substance abuse treatment. Counseling HIV-infected IDUs includes educating them about the importance of safer sex and avoiding needle sharing. Counseling at OTOP departs from usual substance abuse treatment in a number of ways. Family and couples'-counseling may help patients and their families come to terms with the changes associated with HIV disease. Grief counseling helps patients adjust to the deaths of friends or spouses and to fears of their own deterioration or death. Counseling may also help patients cope with grief about other sorts of losses, such as disability. Referring patients to special support groups for HIV-infected patients, such as those for heterosexual drug users, women, or minorities, supplements individual counseling.

Substance abuse treatment programs for HIV-infected patients are necessarily complex because of the number and severity of these patients' problems. Perhaps the most serious of these difficulties is motivating HIV-infected patients to abstain from drug use even though they frequently suffer from anxiety, depression, or demoralization, possibly combined with physical discomfort. Motivation is difficult to instill, but it can be enhanced by motivational counseling that aims to address each patient's own stage of readiness for change.

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Ancillary Services Provided Through Drug Abuse Treatment Settings
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IDUs with HIV disease have far greater needs for medical, psychiatric, and social services than IDUs who are not HIV infected. Because of funding limitations, methadone maintenance treatment programs traditionally provide only a minimum of such services, an approach that is inadequate now that HIV increasingly affects IDUs.

HIV-infected IDUs have a difficult time making and keeping their many appointments with the health-care and social-service providers involved in their treatment. Drug programs must establish liaisons with psychiatric evaluation, psychiatric medical treatment, and HIV-related medical care as well as be prepared to establish such on-site ancillary services at methadone maintenance treatment units.(11,12) Methadone maintenance treatment programs and other drug abuse treatment programs should provide tuberculosis monitoring and treatment. One reason to provide these services is the hope that better day-to-day care for HIV-infected IDUs can reduce in number or severity medical and psychiatric crises requiring hospitalization.

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Stimulant Use
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Cocaine Use
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Cocaine and other stimulant use is common among HIV-infected patients. Cocaine abuse is associated with a high risk of HIV infection because of greater frequency of cocaine injections as compared with opiate use. Because of its shorter half-life and lack of depressant effects, cocaine can be injected ten or more times per day, in contrast to the usual three to five times per day in heroin addiction. The link between cocaine use and HIV transmission may be especially strong among heroin addicts because they may be more likely to inject cocaine than smoke it, thus increasing the chances for infection with shared needles.(22)

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Amphetamines
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Methamphetamine abuse is a serious and growing problem in the United States. Deaths involving methamphetamine use have increased by 61% to 73% between 1992 and 1993.(23,24) Methamphetamine has been closely tied to increased high risk HIV behaviors; in fact, methamphetamine users have the highest rates of HIV seroconversion of any group of drug users in San Francisco.(25)

The risk for HIV infection is due to several factors. Methamphetamine's activating effects may enhance sexual behavior for some individuals and increase impulsivity and sexual risk-taking.(26) Among the reported sexual effects of methamphetamine use are prolonged intercourse and more frequent sex with casual partners.(27) In cities such as San Francisco and Seattle, injection is the dominant route of administration.(28) When methamphetamine is injected, it can lead to the exchange of blood if syringes or other injection materials are shared. Moreover, methamphetamine use appears to be especially popular among gay men, who already have higher rates of HIV risk behaviors than the population at large.(26,29)

Studies have shown that among gay and bisexual men, those individuals who use methamphetamine have significantly higher levels of HIV seroprevalence than other groups at risk.(27,30) In the study by Harris et al, for example, HIV infection was three to four times higher among methamphetamine injectors than among those who did not use methamphetamine. Methamphetamine is prominent among substance-abusing men who reported a close association between drug use and high-risk sexual behaviors, such as unprotected receptive anal intercourse.(31) Methamphetamine use may also serve as a conduit for the spread of HIV from gay men to heterosexual drug users as the latter come into needle-sharing contact with gay or bisexual men.(27)

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Medical Treatments for Stimulant Abuse
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Because stimulant abuse, particularly of cocaine, appears to be an important cofactor in HIV infection for IDUs, adequate medical treatments are essential. There is, however, no generally accepted pharmacologic treatment for cocaine abuse. Although a number of medications for treating stimulant abuse have been proposed or tried in recent years, none has achieved the widespread use of methadone treatment for opiate addiction.

Numerous pharmacotherapeutic treatments have been suggested for stimulant abuse, such as the use of tricyclic antidepressants, particularly desipramine. While some studies have been promising, others have failed to demonstrate the benefits of using desipramine for cocaine-abusing methadone maintenance treatment patients. Other investigators have looked to dopamine agonists, like the antiparkinsonian drugs amantadine and bromocriptine, that decrease the craving for cocaine at the onset of abstinence. Although antidepressants and antiparkinsonian drugs may have some efficacy, there is at this time no firm evidence to support their use or the routine use of any other specific medication for cocaine abuse.(32) The basis for treatment remains psychosocial.

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HIV Medical Care in Drug Users: Behavioral Aspects
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Little evidence exists for significant differences between drug users and other HIV-infected patients in the rate of progression of HIV disease. There are, however, a number of behavioral issues presented by drug users that affect HIV medical care. Patients with drug and alcohol use tend to suffer from behavioral problems associated with their substance use. Behavioral problems associated with substance use include intoxication and withdrawal states, homelessness or unstable housing, criminal activity and misuse of prescriptions, mood disturbances with possible irritability or hostility. Also, disorganization in the face of multiple demands leads to difficulties with appointment keeping and prescription filling. These problems may at times interfere with the ability of a patient to adhere to medical regimens.(20)

In the absence of routine HIV antibody screening, HIV infection is often diagnosed later in the course of illness among drug users than in other HIV-infected patients--typically after the onset of AIDS.(33) Injection drug users may also delay initiating medical treatment, such as antiretroviral medications.(19) This delay may contribute to greater use of expensive emergency medical services and hospitalization rather than to the use of more cost-effective routine outpatient care.(34) AIDS patients who are drug users are more likely to be without a source of primary care and more likely to use emergency medical services than AIDS patients who are not drug users.(35) These problems have led to the use of innovative treatment approaches to provide integrated medical and substance abuse services.

No consistent evidence exists that HIV disease progresses more rapidly in drug users that in non-drug users, although some evidence exists to the contrary.(36) If drug users receive the same level of HIV care in the same clinic as non-drug using HIV patients, there are no differences in disease progression or survival.(37)

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HIV Medical Care Settings for Drug Users
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It is often difficult to adequately coordinate medical services for HIV-infected IDUs, who may have a variety of medical problems. A number of current models are employed to provide primary medical care for HIV patients who are in addiction treatment. One model is to provide medical care by referral of patients to a nearby HIV clinic. This approach may be most effective for patients who are stable, but it may be less appropriate for more complex patients, such as those actively using drugs, who may have minimal or strained relationships with health care providers. Also, IDUs often require ongoing adjunctive care for coexisting psychiatric problems.(38,39) Untreated behavioral problems can interfere with medical care. Drug users may have difficulty keeping appointments, and may be fearful of or ambivalent about medical care.(34) Medical staff in HIV or primary care clinics may not be fully equipped to manage the psychiatric and substance use problems that can interfere with adherence to medical care. If the medical clinic is conveniently and closely situated, however, the referral model can work effectively.(40)

A second model of primary medical care for HIV-infected drug users consists of establishing a substance abuse treatment component at an AIDS clinic. This model would allow HIV-infected IDUs to obtain methadone or other treatment for substance use disorders on-site in a primary care HIV medical clinic. One limitation of this model, however, is the difficulty of responding to the regulatory requirements for methadone treatment.

A third model is to provide on-site primary medical care for IDUs in an addiction treatment facility, such as a methadone maintenance treatment program.(11-13) The methadone treatment setting is efficient for providing medical services in a "one-stop shopping" approach. Referral of patients to off-site primary care clinics can sometimes result in patients failing to reach medical care. In one study,(41) 92% of IDUs in methadone maintenance who were assigned to on-site primary care actually received ongoing medical care, compared to only 35% of patients assigned to a referral. Continued primary medical care for IDUs with HIV infection is critical. For example, Selwyn et al(42) found that the incidence of AIDS was 62% lower among IDUs receiving antiretroviral treatment than among those patients who did not receive such therapy.

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References

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1.   Ball JC, Lange WR, Myers CP, et al. Reducing the risk of AIDS through methadone maintenance treatment. J Health Soc Behav 1988;29:214-226.
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2.   Metzger DS, Woody GE, McLellan AT, et al. Human immunodeficiency virus seroconversion among intravenous drug users in- and out-of-treatment: An 18-month prospective follow-up. J Acquir Immune Defic Syndr Hum Retrovirol 1993;6:1049-1056.
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3.   Weber R, Ledergerber B, Opravil M, et al. Progression of HIV infection in misusers of injected drugs who stop injecting or follow a program of maintenance treatment with methadone. Br Med J 1990;301:1362-1365.
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4.  Center for Substance Abuse Treatment: Selwyn P, Batki, SL. Consensus Panel Co-Chairs. Treatment for HIV-infected alcohol and other drug users. DHHS Publication No. (SMA) 95-3038, Washington DC: U.S. Government Printing Office, 1995.
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5.   Goldstein MJ, Yuen FM. Coping with AIDS: An approach to training and education in a therapeutic community--The Samaritan Village Program. J Subst Abuse Treat 1988;5:45-50.
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7.   Schwartz EL, Brechbul AB, Kahl P, et al. Pharmacokinetic interactions of zidovudine and methadone in intravenous drug using patients with HIV infection. J Acquir Immune Defic Syndr Hum Retrovirol 1992;5:619-626.
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8.  Batki SL, Sorensen JL, Young V. Hospital utilization by HIV+ and HIV- injection drug users before and during methadone treatment. In: Program and Abstracts of the XI International Conference on AIDS, June 1996. Abstract Mo.B.1173.
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9.  United States General Accounting Office. Methadone maintenance: Some treatment programs are not effective; greater federal oversight needed. Report to the Chairman, Select Committee on Narcotics Abuse and Control, House of Representatives. Washington, DC: U.S. Government Printing Office, 1990.
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10.   Batki SL. Treatment of intravenous drug users with AIDS: The role of methadone maintenance. J Psychoactive Drugs 1988;20:213-216.
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11.   Selwyn PA, Feingold AR, Iezza A, et al. Primary care for patients with human immunodeficiency virus (HIV) infection in a methadone maintenance treatment program. Ann Intern Med 1989;111:761-763.
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12.  Goosby E, Batki SL, London J, et al. Medical care of HIV disease in methadone maintenance treatment. In: Harris LS, ed. Problems of Drug Dependence, 1991. Washington, D.C.: NIDA Research Monograph Series, 1992;119:431.
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13.   Selwyn PA, Budner NS, Wasserman WC, et al. Utilization of on site primary care services by HIV-seropositive and seronegative drug users in a methadone maintenance program. Pub Health Rep 1993;108(4):492-500.
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14.  Batki SL, Ferrando SJ, Manfredi LB, et al. Psychiatric disorders, drug use, and medical status in injection drug users with HIV disease. Am J Addict 1996;5:249-258.
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15.   Lyketsos CG, Federman EB. Psychiatric disorders and HIV infection: Impact on one another. Epidemiol Rev 1995;17:152-164.
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16.   Chesney MA, Lurie P, Coates TJ. Strategies for addressing the social and behavioral challenges of prophylactic HIV vaccine trials. J Acquir Immune Defic Syndr Hum Retrovirol 1995;9:30-35.
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17.  Fischl MA. Adherence in the safety and efficacy study of zidovudine in the treatment of subjects with mildly symptomatic HIV. Presented at the Conference of Adherence in AIDS Clinical Trials, San Francisco, CA, April 1991.
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18.   Samet JH, Libyan H, Stager KA, et al. Compliance with zidovudine therapy in patients infected with human immunodeficiency virus, type I: A cross-sectional study in a municipal hospital clinic. Am J Med 1992;92:495-502.
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19.   Broers B, Morabia A, Hirschel B. A cohort study of drug users' compliance with zidovudine treatment. Arch Intern Med 1994;154:1121-1127.
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20.   Wall TL, Sorensen JL, Batki SL, et al. Adherence to zidovudine (AZT) among HIV-infected methadone patients: A pilot study of supervised therapy and dispensing compared to usual care. Drug Alcohol Depend 1995;37:261-269.
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21.  Sorensen JL, Mascovich A, Wall TL, et al. Medication adherence strategies for drug abusers with HIV disease. AIDS Care, In press.
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22.   Chaisson RE, Bacchetti P, Osmond D, et al. Cocaine use and HIV infection in intravenous drug users in San Francisco. JAMA 1989;261:561-565.
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23.  U.S. Dept. of Health and Human Services (USDHHS), Substance Abuse and Mental Health Service Administration (SAMSHA): Annual Medical Examiner Data 1993: Data from the Drug Abuse Warning Network (DAWN), Series I, No. 13-B: DHHS Pub. (SMA)95-3019. Washington DC: U.S. Government Printing Office, 1995.
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24.  National Institute on Drug Abuse (NIDA). Statistical Series: Annual Emergency Room Data 1991 -- Data from the Drug Abuse Warning Network (DAWN). DHHS Pub. (ADM)92-1955. Washington, DC: U.S. Government Printing Office, 1992.
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25.  San Francisco Department of Public Health Community Substance Abuse Services (SF DPH/CSAS): Stimulant Abuse in San Francisco: Status Reports on Cocaine and Methamphetamine Problems. Department of Public Health, Community Substance Abuse Services, 1996.
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26.   Gorman M. Speed use and HIV transmission. Focus, June 1996;:4-6.
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27.   Harris NV, Thiede H, McGough JP, et al. Risk factors for HIV infection among injection drug users: Results from blinded surveys in drug treatment centers, King County, Washington, 1988-1991. J AIDS 1993;6(11);1275-1282.
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28.  U.S. Dept. of Health and Human Services (USDHHS), Substance Abuse and Mental Health Service Administration (SAMSHA): Methamphetamine abuse increases. SAMSHA News 1996;Winter/Spring:29-30.
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29.  Gorman EM, Morgan P, Lambert E. Qualitative research considerations and other issues in the study of methamphetamine use among men who have sex with other men. NIDA Research Monograph Series 1995;157:156-171.
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30.   Sorvillo F, Kerndt P, Cheng KJ, et al. Emerging patterns of HIV transmission: The value of alternative surveillance methods. J Acquir Immune Defic Syndr Hum Retrovirol 1995;9(6):625-629.
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31.   Paul J, Stall R, Davis F. Sexual risk for HIV transmission among gay/bisexual men in substance abuse treatment. AIDS Educ Prev 1993;5(1):11-24.
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32.   Mendelson JH, Mello NK. Management of cocaine abuse and dependence. N Engl J Med 1996;334(15):965-972.
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33.   Hu DJ, Byers Jr R, Fleming PL, et al. Characteristics of persons with late AIDS diagnosis in the United States. Am J Prev Med 1995;11:114-119.
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34.   Solomon L, Frank R, Vlahov D, et al. Utilization of health services in a cohort of intravenous drug users with known HIV-1 serostatus. Am J Public Health 1991;81:1285-1290.
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35.   Mauskopf J, Turner BJ, Markson LE, et al. Patterns of ambulatory care for AIDS patients, and association with emergency room use. Health Serv Res 1994;29:489-510.
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36.   Eskild A, Magnus P, Sohlberg C, et al. Slow progression to AIDS in intravenous drug users infected with HIV in Norway. J Epidemiol Community Health 1994;48:383-387.
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37.   Chaisson RE, Keruly JC, Moore RD. Race, sex, drug use, and progression of human immunodeficiency virus disease. N Engl J Med 1995;333:751-756.
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38.   Brettle RP, Nelles B. Special problems of injecting drug-misusers. Br Med Bull 1988;44:149-160.
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39.   Batki SL. Drug abuse, psychiatric disorders, and AIDS -- Dual and triple diagnosis. West J Med 1990;152:547-552.
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