Providers of medical care to people who are HIV-infected and who abuse alcohol and other drugs (AODs) face several significant challenges: overcoming the systemic and emotional barriers that keep many of these patients out of the healthcare system, empowering patients who enter the system to be active participants in their own care, and keeping abreast of the latest recommendations concerning the care of HIV-infected individuals at a time when knowledge of the nature and course of HIV infection is evolving rapidly.
Both HIV and AOD abuse are chronic diseases, and there are many similarities between HIV care and AOD abuse treatment. Yet, an uneasy relationship frequently exists between the fields of medicine and AOD abuse treatment. Staff of AOD abuse treatment programs may see a focus on medical care for HIV infection as counterproductive to patients' recovery from AOD abuse. Medical providers may harbor judgmental attitudes about AOD abusers. In turn, AOD abusers may distrust their medical care providers (Gerbert et al., 1991).
Clinical experience demonstrates, however, that patients with both AOD addiction and HIV infection need integrated care to attain satisfactory outcomes. The need for integrated treatment of HIV infection and AOD abuse must be continually emphasized to both patients and healthcare providers. Providers in medical care and AOD abuse treatment settings have a responsibility to overcome their differences in the interests of their patients.
Bringing AOD abusers with HIV infection into the healthcare system is a significant challenge. Several studies have shown that most HIV-infected AOD abuse patients delay seeking medical care. In one study, 24 percent of HIV-positive patients waited more than a year after learning of their status to present for primary care. The median CD4+ cell count of these patients at presentation was in the 300s, below the threshold at which HIV-related medical therapy should be considered (Samet et al., 1992b).
Why patients wait so long to seek treatment is not well understood. Factors such as lack of financial resources, lack of health insurance, shortage of treatment slots, and the difficulty of navigating the treatment system probably play a part. In addition, individuals may be reluctant to enter a healthcare system they perceive as unsympathetic.
The structure of many healthcare systems and the behavior of many healthcare providers can reinforce AOD abusers' view of themselves as failures. Individuals' feelings of helplessness about addressing their AOD abuse may feed into a general sense of helplessness about taking care of their health problems. Denial may also cause individuals to minimize their medical problems in general, and HIV infection in particular. When HIV-infected AOD abusers do seek medical attention, they tend to make excessive use of acute and emergency care services and to underuse primary care medical services.
To achieve integration of care for HIV-infected AOD abuse patients, linkages must be developed and communication maintained between providers of AOD abuse treatment and HIV medical care. Existing links between primary medical care and substance abuse treatment (such as those that have been established in some managed care organizations) must be built upon to expand services and improve access to care (Selwyn et al., 1989, 1993; O'Connor et al., 1992).
The 1993 Substance Abuse Prevention and Treatment Block Grants: Interim Final Rule reinforces the importance of linkages between AOD treatment and primary care services, particularly in the provision of services to injecting drug users (IDUs). For example, the regulations require that IDUs on a waiting list for AOD treatment receive interim services within 48 hours of requesting them. Interim services must include referrals to HIV healthcare services as well as HIV counseling and education. (See summary of interim block grant regulations in Appendix B. See also list of resources in Appendix G.)
All AOD abuse treatment programs should be capable of conducting HIV risk assessments and providing basic HIV education and counseling to patients. In addition, all programs should provide access to HIV testing and pre- and posttest counseling. If programs cannot provide testing and related counseling onsite, they must have formal relationships with other agencies that will provide these services for patients referred by the program.
For guidance on structuring HIV counseling programs, providers should consult the U.S. Centers for Disease Control and Prevention (CDC) Technical Guidance on HIV Counseling (CDC, 1993f.)
Staff of primary care facilities serving HIV-infected AOD abuse patients should understand and be responsive to these patients' needs (Libman et al., 1992;Samet et al., in press). They should be aware that a patient's relapse into AOD abuse may result in noncompliance with medical care. In addition, staff must be sensitive to cultural variations and issues surrounding race and ethnicity, sexual orientation, life experiences, and gender. (See section on cultural competence of providers in Chapter 1.)
Providers of primary care for HIV-infected persons should ask questions about the status of their AOD abuse. Patients need continual reinforcement of the message that, by continuing to abuse AODs, they are further damaging their own health as well as placing others at risk of HIV infection. Many of the skills used in HIV treatment are also inherent in AOD abuse treatment. For example, treatment of both disorders should emphasize survival, assertiveness, and patients' empowerment to address their illnesses.
Chapter 2 of this Treatment Improvement Protocol (TIP) provides an overview of AOD abuse treatment settings and modalities. Exhibit 3-1 contains a description of the various models for the provision of medical care in AOD abuse treatment programs.
Few well-defined models exist for providing primary care to HIV-infected AOD abuse patients within AOD abuse treatment programs. Unfortunately, much of this population's medical care occurs in hospital emergency departments. Finding primary care physicians or clinics willing to accept HIV-infected AOD abuse patients can be a major problem.
There is a need to evaluate existing models of primary care to identify how they can be modified and expanded to address the special needs of the HIV-infected AOD abuse population (O'Connor et al., 1992;Selwyn et al., 1993). There have been no studies of outcomes for patients referred to available community primary care resources. One study that compared onsite with offsite primary care for a small group of subjects found that onsite care provided in an AOD treatment setting had significant advantages (Umbricht-Schneiter et al., 1994).
From 1989 to 1992, the Health Resources and Services Administration (HRSA) and the Center for Substance Abuse Treatment (CSAT) funded 15 demonstration projects linking primary care services and AOD abuse treatment. Information about the Ryan White Comprehensive AIDS Resources Emergency Act of 1990 (the CARE Act) is provided in Appendix E.
AOD abuse treatment programs that have developed onsite provision of primary care medical services have tended to be hospital- or university-affiliated programs able to benefit from a close association with affiliated medical specialists. Experience with such onsite systems demonstrates them to be beneficial where the resources exist to establish and maintain them. (See Exhibit 3-2 and accompanying box outlining the services at Substance Abuse Services, the clinic for HIV-infected AOD abuse patients at the San Francisco General Hospital.)
Few AOD abuse treatment programs have sufficient resources to provide onsite HIV primary care services. It is recommended that programs without such resources establish referral systems to provide primary healthcare services through linkages with community healthcare centers, public health clinics, private providers, or hospitals. Boston City Hospital has operated an exemplary program with well-established linkages since 1990; see accompanying box.
The practice of distributing patients to various clinical sites for primary care has been referred to as a distributive care system (Samet et al., in press). Optimally, such a system should be multidisciplinary, with social workers, physicians, physicians-in-training, nurses, and counselors included among the treatment staff. A case manager may be helpful in facilitating a referral system.
Communication. When patients are sent to referral sites for primary medical care, a communication system should be in place to ensure that appointments are kept and that information about patients' medical care is sent back to the referral point. A memorandum of understanding (MOU) between the referral site and the primary care provider is recommended to ensure that this feedback occurs systematically.
The 1993 Substance Abuse Prevention and Treatment Block Grants: Interim Final Rule requires States to coordinate AOD prevention and treatment activities with other services, including HIV services. MOUs may be cited as evidence that such coordination is being sought. (See summary of block grant interim regulations in Appendix B.)
Some HIV services may be provided by contractual arrangement with other healthcare facilities. For example, patients with identified health problems, such as positive tuberculin skin test results, may be sent to a local hospital or other facility with which the referring facility has a contractual arrangement. The contractual arrangement guarantees that the patient will be seen and specifies the services to be rendered. Unlike referrals, contractual arrangements contain a built-in mechanism that ensures continuity of care.
Recommended elements of a contractual arrangement for primary medical care services are described in Exhibit 3-3.
As noted in the introduction to this chapter, knowledge about the nature and course of HIV infection is evolving rapidly. There remain, however, many unanswered questions concerning what constitutes optimal treatment for HIV disease itself and some of its manifestations. As a result, a range of acceptable clinical practice exists.
The purpose of this section of the Treatment Improvement Protocol (TIP) is to describe that range of practice endorsed by the CSAT consensus panel members. This is not a treatment handbook, however. Where specific treatment recommendations exist, or where data strongly indicate that a particular intervention is superior to alternative treatments, that information is clearly stated. Where there are arguments for and against a particular intervention, both the advantages and disadvantages are discussed.
The panel's intent is to provide clinicians treating HIV-infected AOD abuse patients with current information on which to base clinical decisions that are in the best interests of their patients. The reader is also referred to several excellent sources of information on current HIV/AIDS care, with special reference to primary care and outpatient management (Advisory Group on HIV Early Intervention, 1994; Agency for Health Care Policy and Research, 1994; Broder et al., 1994; Gallant et al., 1994; Jewett and Hecht, 1993; Hecht and Soloway, 1992-1993; Libman and Witzburg, eds., 1993).
In 1993, CDC established a new classification system for HIV infection and AIDS, replacing earlier systems. The new classification system includes a matrix of clinical and laboratory parameters that enable physicians to categorize patients according to disease severity. CDC also expanded its list of AIDS-defining conditions to include a CD4+ cell count of less than 200, cancer of the cervix, pulmonary tuberculosis, and recurrent bacterial pneumonia (CDC, 1992a) as AIDS-defining conditions in HIV-seropositive persons (see Exhibit 3-4).
These changes were intended in part to remedy the underestimation of AIDS incidence in IDUs, people of color, and women that occurred under previous classification systems. Preliminary analysis of the impact of these definitional changes on the reporting of AIDS cases indicates that these groups are better represented in the newly included clinical categories than formerly.
Clinicians should become familiar with the new HIV/AIDS classification system, not only because of its clinical implications, but also because patients' eligibility for social service entitlements may be linked for certain conditions to the revised HIV/AIDS case definition.
The natural history of HIV infection suggests that the great majority of infected persons will eventually develop AIDS. Although there are wide individual variations, current epidemiological data suggest that the average time from initial infection with HIV to the development of clinical AIDS -- in the absence of preventive interventions -- is at least 10 years. It has also been clearly shown that both antiretroviral therapy (i.e., anti-HIV therapy) and prophylactic regimens against opportunistic infections such as Pneumocystis carinii pneumonia (PCP) can increase the length of the asymptomatic period and in some cases have a favorable impact on survival once patients become symptomatic (Graham et al., 1991, 1992; Lundgren et al., 1994;Moore et al., 1991; Osmond, 1994).
Although there has been much recent controversy concerning the appropriate timing of initiation of antiretroviral therapy, it is clear that a fundamental change has taken place over the last decade in the medical approach to HIV infection and disease. It is now appropriate to think of HIV infection and AIDS as chronic conditions requiring ongoing care and management. This approach contrasts sharply with the situation in the early years of the HIV epidemic, when AIDS frequently presented as a fulminant illness with high short-term mortality.
This change has important implications for AOD treatment programs, which can expect to see an increasing proportion of patients with HIV infection, both asymptomatic and symptomatic, in treatment over long periods of time. The rationale for incorporating comprehensive HIV care into AOD treatment programs will only grow stronger in coming years. (See Exhibit 3-5.)
As noted in Chapter 1 of this TIP, wide variations exist in the prevalence of HIV infection among AOD abusers with respect to geographic region, demographic factors, and sampling context. It is clear, however, that chemically dependent persons -- particularly IDUs -- are at high risk for acquiring HIV. In addition to the central role of shared needle use as a vector for HIV transmission, substance use increases the risk of infection with HIV by reducing individuals' inhibitions and increasing the likelihood that they will engage in high-risk sexual practices. Half of all AIDS cases diagnosed in women in the United States to date have been in female AOD users.
Many AOD abusers may be unaware that they are HIV-infected. Individuals at risk of HIV infection are often reluctant to be tested because of denial, fear of stigmatization, or a belief that "nothing can be done." However, early identification of HIV-infected persons is important both for public health reasons and because patients can benefit from early medical intervention:
Risk reduction education can prevent transmission of HIV by encouraging infected individuals to adopt safer sex and drug-using practices.
TB screening and prophylaxis can prevent progression to active TB and transmission of this highly infectious condition to others. IDUs are at risk of being coinfected with HIV and TB.
Vaccinations recommended in HIV-infected persons (for pneumococcal pneumonia, influenza, and hepatitis B) are more effective when administered early in the course of HIV infection, before patients' immune systems are severely compromised.
Zidovudine therapy and, increasingly, therapy with other antiretroviral medications may play a role in helping to prevent disease progression and improving immune function. Zidovudine is now recommended for HIV-infected pregnant women because it has been shown to reduce perinatal transmission of HIV from mother to infant.
Prophylaxis against opportunistic infections, particularly PCP has clearly been shown to be an effective, safe, and simple strategy for reducing morbidity and mortality from certain common HIV-related diseases.
AOD abuse treatment programs should encourage their patients to be tested for HIV infection. If onsite testing is not feasible, programs should develop linkages with HIV testing facilities. However, patients have a right to refuse HIV testing and cannot legally be denied AOD treatment if they so refuse. (See Chapter 7.)
CD4+ T-lymphocytes (also referred to as CD4+ cells, T-cells, or T-4 helper cells) are the subset of white blood cells in the immune system specifically targeted by HIV. Although HIV also infects other types of cells, it is the virus's effects on CD4+ cells that cause most of the immunosuppression characteristic of HIV disease.
CD4+ cell counts are generally relied upon as surrogate markers for the stage of a patient's HIV disease. A normal CD4+ count is in the range of 800 to 1,500. However, for several reasons, it is advisable that clinicians not attach excessive importance to CD4+ counts. Although they reflect the overall status of the immune system and are presumed to reflect the stage of illness, CD4+ counts can fluctuate over time. Results can also vary among different laboratories and be affected by factors such as intercurrent (coexisting or intermittent) illness and time of day. Measuring CD4+ counts during acute intercurrent illness is generally not recommended.
Also, CD4+ counts are only an indirect measure of viral activity. They measure the effects of the virus on the target cell, not the activity or virulence of the virus itself. Within the next 1 or 2 years, commercial blood tests that measure HIV viral activity more directly should become available. These new tests, which will be able to quantify viral levels in blood and determine strain type and other indicators of virulence, should have great clinical utility. For the time being, however, CD4+ lymphocyte counts are the best available measure of the extent of HIV-related immune suppression and disease progression. To obtain the most accurate information about trends in a patient's CD4+ levels over time, counts should be taken twice initially at intervals a few days apart and periodically thereafter. Long-term therapy can be based on the results of these tests. Exhibit 3-6 shows recommended CD4+ testing frequencies and thresholds for initiating antiretroviral therapy.
The CD4+ percent, or the percentage of lymphocytes that are CD4+ helper cells, is an additional measurement often performed as part of basic CD4+ lymphocyte subset studies which include the CD4+ helper cell count. The CD4+ percent may display less variability than the CD4+ count.
In seeing HIV infection as a chronic rather than a terminal illness, clinicians need to be sensitive to the emotional overtones of CD4+ counts for HIV-infected patients. Patients may become overly invested in the meaning of a particular CD4+ count, distorting its importance within the context of their overall condition. Patients with low CD4+ counts can be relatively healthy and stable, while those with high counts can be clinically ill. It is recommended that information about a patient's CD4+ count be conveyed sensitively and within the context of the patient's overall clinical picture.
Despite their limitations, CD4+ measurements are useful in indicating points at which treatment decisions must be made (for example, when counts are declining faster than expected or when they reach certain set points). The average yearly decline of CD4+ cell counts in HIV-infected patients -- particularly during the long period after primary infection and before the very late stages of illness, when absolute CD4+ declines may be greater and smaller, respectively -- is 60 to 85 cells per year.
However, the rate of decline is variable. Some patients' CD4+ counts decline rapidly while others remain stable for long periods. There is no evidence that CD4+ counts decline more rapidly in HIV-infected AOD abusers than in other HIV-infected populations (Graham et al., 1992; Margolick et al., 1992; Saag, 1994a).
Medical care provided to HIV-infected individuals will vary depending on the stage of the infection, but all patients should receive a minimum level of evaluation and followup (Jewett and Hecht, 1993). An assessment of behavior associated with transmission of HIV is an important part of the initial patient assessment. Medical providers need to be aware of the risks associated with activities, such as unsafe sex and drug practices, in which patients may engage.
At initial presentation and periodically thereafter, all AOD abuse patients should receive risk assessments and comprehensive medical examinations. These examinations may be performed onsite or at another facility through referral or a contractual arrangement. (See above, Models of Medical Care for an AOD Abuse Population, p. 20.)
As mentioned in the introduction to this chapter, staff of primary care facilities serving HIV-infected AOD abuse patients need to understand and be responsive to these patients' needs. They should be aware that a patient's relapse into AOD abuse may result in noncompliance with medical care. In addition, staff need to be sensitive to cultural variations and issues surrounding race and ethnicity, sexual orientation, life experiences, and gender. (See data regarding cultural sensitivity and competence, Chapter 1, Appendix D.)
A thorough medical history is an important first step that enables the provider to proceed to clinical evaluation and formulation of a treatment plan. Taking the history may occupy an entire patient visit, particularly when it is combined with education and counseling. If the HIV test occurred elsewhere, it might be helpful to begin by inquiring when the patient took the test and why. This query may elicit some information about the patient's medical history and risk behaviors. Questions about drug use and sexual practices should be explicit and clear. Documentation of the HIV-positive test result, if performed elsewhere, should also be obtained and noted in the record.
Sometimes the risk history will provide an indication of the duration of the patient's infection. If so, the provider may wish to discuss the usual latency period of HIV and implications of the patient's history for determining the stage of the disease and the prognosis. Patients should be thoroughly counseled on risk reduction and encouraged to notify past and present sexual or drug use contacts of their HIV status. Contact notification is a difficult issue for many patients, but most people can be persuaded to cooperate once they understand that their contacts may be at serious risk.
The next step in the history taking may be to ask questions about specific symptoms of HIV infection (for example, fevers, night sweats, diarrhea, weight loss, lymphadenopathy, thrush, vaginitis, or skin changes) or symptoms suggesting undiagnosed AIDS-defining conditions (for example, mental status changes, visual changes, severe headaches, chronic diarrhea, shortness of breath, or difficulty swallowing).
Questioning about past medical history should particularly cover previous diagnoses and/or treatment of tuberculosis, syphilis, genital herpes, and (in women) abnormal Pap smears. It is important to address sexual behavior in HIV-infected AOD abusers because of the prevalence of sexual disinhibition related to AOD use. Sexually transmitted diseases (STDs) are common in AOD abusers, particularly among women involved in commercial sex work or the exchange of sex for drugs.
The patient's immunization history should be recorded.
Specific information should be collected about the patient's social situation, including functional status, housing, employment, health insurance, and social support from family members or significant others. These questions may identify urgent social needs and prompt immediate referral to a social service agency or provider.
At the conclusion of the visit, a tuberculin skin test should be done, a set of laboratory tests performed or ordered, and one or more needed immunizations given. (See Exhibit 3-7 and text.) At the next visit, a full physical examination can be done and lab results reviewed.
A careful physical examination is an essential part of the initial evaluation of HIV-infected patients. The physical exam can result in the diagnosis at an asymptomatic stage of a variety of complications that present a significant risk in this patient population. The exam also provides baseline data on which future clinical decisions may be based.
Fevers are common in HIV-infected patients and may be an indication of opportunistic infection. Weight loss greater than 10 percent of body weight, combined with chronic fever or diarrhea, establishes the AIDS-defining "wasting syndrome."
Cytomegalovirus retinitis is a common complication associated with changes in or loss of vision that is almost always seen in patients whose CD4+ counts are below 100.
Thrush and other oral lesions are also exceedingly common. Thrush should be treated with antifungal agents, for example, nystatin, clotrimazole, or fluconazole; it is also an indication for starting PCP prophylaxis, even if the CD4+ count is above 200.
Regular examination of lymph nodes should be considered. Lymphadenopathy in persons with HIV infection is not always caused by HIV alone. Fine-needle aspiration of lymph nodes in patients with marked or rapidly increasing adenopathy may lead to a treatable diagnosis.
Skin abnormalities are common. A regular examination of the entire skin surface may reveal treatable conditions ranging from seborrheic dermatitis to Kaposi's sarcoma.
Because women with HIV infection may have a high prevalence of cervical abnormalities, regular Pap smears -- every 6 months or at least annually -- are advised. In sexually active women, the pelvic exam should include testing for gonorrhea and chlamydia because these infections may increase the risk of pelvic inflammatory disease.
Limited information is available on which to base recommendations for the routine use of most laboratory studies in HIV-infected patients. These suggestions should be adapted to the particular circumstances of the individual patient and physician.
CD4+ counts. As noted above, CD4+ counts at present remain the standard laboratory test to assess the level of immune dysfunction in HIV-infected patients. As mentioned, it is preferable if possible to perform two CD4+ tests a few days apart to help determine a baseline and assess patients' eligibility for antiretroviral therapy more accurately.
Blood counts. A complete blood count (CBC) can alert the clinician to blood abnormalities common in HIV-infected patients, including anemia, leukopenia, and thrombocytopenia. In patients receiving zidovudine, the frequency of CBCs is determined by the need to monitor for hematologic toxicity. In symptomatic patients not on zidovudine, CBCs can be repeated at 3- to 6-month intervals; in asymptomatic patients not on zidovudine, repetition every 6 to 12 months is advised.
Screening chemistries. Routine screening chemistries are recommended annually. Testing at 2- to 4-month intervals is indicated in patients receiving medications with potential liver, kidney, and muscle toxicity.
Syphilis. Annual serologic screening for syphilis is recommended.
Toxoplasmosis. Baseline testing is useful to identify patients with past exposure to toxoplasma, who may benefit from prophylaxis against this infection. Without prophylaxis, such patients have about a 30 percent chance of developing cerebral toxoplasmosis in the course of their HIV infection (especially when CD4+ counts drop below 100). Annual testing is advised in patients without prior exposure.
Hepatitis B virus (HBV). The prevalence of past exposure to HBV approaches 90 percent in many HIV-infected AOD populations in the United States. Because of the cost of the HBV vaccine, it may be cost effective to screen patients for exposure to this virus to determine if vaccination is necessary; vaccination is indicated for HIV-infected patients without previous exposure (i.e., all markers negative).
Hepatitis A and C. Injection drug users (IDUs) are also at risk for hepatitis A infection (although the reason for this has not been determined) and hepatitis C infection, which is parenterally transmitted like hepatitis B. While no effective treatment exists for either one of these conditions (hepatitis A is usually benign and self-limited, and hepatitis C may be treated with injected interferon-alpha, but this treatment is expensive and impractical and often causes unpleasant side effects), it may be helpful to determine the presence of prior viral hepatitis in patients likely to be exposed to increasing numbers of hepatotoxic medications used to treat HIV disease. This determination may be particularly important for hepatitis C, which appears to persist as a chronic, active infection much more commonly than is the case for hepatitis B.
Chest x-ray. A chest x-ray is optional in the initial patient evaluation. Routine chest x-rays have been advocated to provide a "baseline" when patients present with respiratory symptoms, but there are no studies to support this recommendation. CDC suggests performing routine chest x-rays in anergic patients to look for signs of latent TB. Chest x-rays may also be useful in patients with a past history of pulmonary disease or heavy smoking.
Clinicians providing care to HIV-infected AOD abusers must be familiar with the clinical manifestations of HIV disease and aware that these manifestations can be difficult to distinguish from common medical complications of substance abuse. Differential diagnoses in HIV-infected AOD abusers can be challenging because both HIV infection and substance abuse have clinical effects on a wide range of organ systems. To provide optimal care to this population, clinicians must be fully aware of the medical effects of both substance abuse and HIV infection (O'Connor et al., 1994). Exhibit 3-8 lists common symptoms that may be related to either HIV infection or AOD abuse.
Anorexia, weight loss, and fatigue may be a complication of chronic cocaine use, may be caused by HIV infection, or may be symptoms of specific AIDS-related opportunistic infections (for example, Mycobacterium avium complex, cytomegalovirus, tuberculosis). Tachycardia, flu-like illness, fatigue,abdominal pain, and diarrhea may be symptoms of drug withdrawal, particularly opioid withdrawal, or they may be symptoms of acute or chronic HIV-related conditions.
Chest pain, coughing, and shortness of breath may be symptoms of "crack" cocaine use or of HIV-related pulmonary infections such as PCP. Bacterial endocarditis with fever, night sweats, and chest pain or other pulmonary effects may result from unsterile intravenous injection or may indicate HIV-related opportunistic infection. Heavy cigarette smoking in IDUs may also make it difficult to interpret symptoms such as shortness of breath or the results of pulmonary function tests.
HIV and its related opportunistic infections commonly affect the nervous system, resulting in conditions such as HIV-related dementia, central nervous system cryptococcoses and toxoplasmosis, and HIV-related peripheral neuropathy. Drug intoxication or withdrawal can also have direct effects on consciousness, cognition, and behavior. Heroin and cocaine use may be responsible for stroke syndromes and other cerebrovascular disease. Alcoholic, nutritional, and traumatic peripheral neuropathy syndromes may also be more common in substance abusers than in the population as a whole.
As previously noted, HIV disease now fits the pattern of a chronic disease (with exacerbations and remissions) rather than a fulminant illness presenting suddenly and progressing rapidly to death. Patients require periodic use of acute care services and inpatient resources, especially in the latter stages of the disease. Over the last decade, however, as patients have experienced longer asymptomatic periods between illnesses, there has been an increasing emphasis on outpatient management and primary care for HIV infection.
Care strategies have incorporated both antiretroviral therapy and a wide range of prophylactic regimens to effectively prevent opportunistic infections. A recent study found, however, that preventive interventions such as TB prophylaxis and pneumococcal vaccine were used by only about 30 percent of eligible patients; use of preventive interventions was lowest among HIV-infected IDUs (Glassroth et al., 1994). (See Exhibit 3-9.)
Zidovudine (AZT) remains the first-line drug of choice in treating HIV infection; it is also the agent with which clinicians and researchers have the most experience. Zidovudine (one of a class of medications known as reverse transcriptase inhibitors) first entered clinical practice in 1987, when it was shown to decrease disease events and prolong survival in patients with symptomatic HIV infection and AIDS (Fischl et al., 1987).
In 1989, based on a multicenter trial in the United States conducted through the NIH-funded AIDS Clinical Trials Group, it was recommended that all patients with CD4+ counts of less than 500 should receive zidovudine, whether they were symptomatic or not. This recommendation was based on the observation that patients who received zidovudine progressed to AIDS more slowly than patients on placebo.
However, the drug had no impact on mortality. The overall burden of morbidity and mortality was low in the asymptomatic group, even among placebo recipients, compared with previous observations in patients with late-stage disease (Volberding et al., 1990;Fischl et al., 1990).
Conflicting study results. Subsequent studies also demonstrated zidovudine's efficacy in delaying HIV disease progression in mildly symptomatic patients. Several other studies, however, including the United States Veterans Administration trial and the more recent European "Concorde" trial, showed no clearcut benefit to zidovudine therapy in asymptomatic patients. Specifically, in the Concorde trial, immediate versus delayed therapy with zidovudine in asymptomatic patients conveyed no clearcut long-term survival benefit (Hartigan, et al., 1992;Aboulker and Swart, 1993).
However, a recent collaborative European-Australian trial did find benefit from the use of zidovudine in patients with CD4+ counts above 400. In this study, patients receiving zidovudine had a decreased rate of disease progression compared with a placebo group (Cooper et al., 1993 ). Further, there have been consistent clinical observations that zidovudine may be of greatest benefit in the first 1 to 2 years after initiation of therapy. Patients frequently show evidence that the medication's effectiveness declines over time (for example, CD4+ counts increase but later decline; new opportunistic infections occur, etc.) (Lundgren, et al., 1994;Osmond, et al., 1994).
Given these varying observations, it is understandable that there has been confusion concerning the appropriate use of zidovudine. However, recent studies suggest that withholding therapy in the asymptomatic phase may have potentially adverse consequences, just as there may be adverse consequences to initiating therapy before patients become clinically symptomatic. It has been observed, for example, that active HIV replication occurs within lymph nodes during the clinically latent phase of disease. Although the patient is asymptomatic, the total viral burden of HIV is growing steadily, with increasing destruction of lymph node elements in the immune system (Fauci, 1993;Pantaleo et al., 1993).
Benefits of therapy. Despite the conflicting conclusions reached in different trials, evidence is generally consistent that once zidovudine therapy is initiated, patients experience a longer asymptomatic period and reduced frequency of disease events during the first year or several years they use the medication (Osmond et al., 1994;Lundgren, et al., 1994). It is also clear that use of zidovudine in the later stages of HIV disease confers a survival benefit.
The initiation of antiretroviral therapy should be presented to the patient as a choice and its potential advantages and disadvantages discussed fully. Many patients and clinicians would still opt for the use of a medication that is likely to result in several years' reduced morbidity in the hope that additional therapies become available to supplement or ultimately replace zidovudine. Clinicians and patients making decisions about initiating antiretroviral therapy with zidovudine may wish to consider that development and approval of additional types of antiretroviral agents are expected within 2 to 4 years (Saag, 1994b).
Other antiretroviral agents. Three other medications from the reverse transcriptase inhibitor class are now available for clinical use: didanosine (ddI), zalcitabine (ddC), and stavudine (d4T). Zidovudine has been shown to be the most effective agent for initial antiretroviral therapy, but several recent studies have examined the use of didanosine and/or zalcitabine, either alone or in combination with zidovudine after an initial period of zidovudine use (Abrams, 1994;Collier et al., 1993;Spruance et al., 1994).
It has become increasingly common for clinicians to use one of these agents either in combination with or as an alternative to zidovudine when patients develop zidovudine intolerance or when their HIV disease continues to progress while they are taking zidovudine. Clinical practice in this area is continually evolving.
Preliminary data support the rationale for combination therapy. This approach is consistent with therapeutic approaches to tuberculosis and other chronic infections for which the emergence of drug resistance is decreased by the use of multiple agents.
Unfortunately, the currently available antiretroviral agents are all reverse transcriptase inhibitors, i.e., they all act at the same stage of the viral life cycle of HIV. The development of protease inhibitors, which attack viral replication at a later stage in the cycle, is soon expected to provide an additional class of agents that may work effectively in combination with the reverse transcriptase inhibitors.
Recommendations. A National Institute of Allergy and Infectious Diseases (NIAID) consensus panel recommended in late 1993 that zidovudine therapy be considered for asymptomatic patients with CD4+ counts between 200 and 500 and recommended to symptomatic patients and those with CD4+ counts of less than 200 (Sande et al., 1993). (See accompanying Quick Reference Summary.)
The current dosage of zidovudine generally recommended in the literature is 100 mg five times daily as a chronic regimen. However, alternative regimens, such as two capsules (100 mg) three times daily (i.e., 600 mg/day), are frequently prescribed and may be preferable if patients find it easier to comply.
Recent data indicate that zidovudine therapy may play a key role in preventing the perinatal transmission of HIV from mothers to infants (CDC, 1994a).
The NIAID panel also recommends substituting didanosine or zalcitabine for zidovudine in patients whose disease is progressing or who are intolerant to zidovudine. In a recent study, didanosine and zalcitabine demonstrated comparable efficacy when used as single agents in patients who were either not responding to or could not tolerate zidovudine (Abrams, 1994). In practice, as noted above, clinicians frequently prescribe one of these agents in addition to zidovudine.
No formal NIAID recommendation exists concerning the use of stavudine, which was licensed by the Food and Drug Administration (FDA) in August 1994. In practice, however, stavudine is used to treat advanced HIV disease in patients who are intolerant to or worsening on other antiretroviral medications. It is not yet routinely used in combination therapy.
Side effects. Side effects of zidovudine include headaches, nausea, myalgias, and insomnia. Because side effects may affect adherence to the prescribed regimen, clinicians should discuss them with patients before initiating therapy. For many AOD abusers, the side effects of zidovudine mimic those of withdrawal from substances of abuse, especially opioids. Lowering the dosage may decrease side effects and achieve better patient adherence. The lowest effective daily dose is probably close to 300 mg/day; at this dosage level, full adherence to therapy becomes critical. More serious complications of zidovudine therapy include anemia, granulocytopenia, myopathy, and (rarely) hepatitis. Most of these complications are dose related.
Significant side effects of didanosine are gastrointestinal distress (for example, abdominal pain and diarrhea) and numbness and tingling in the extremities. Didanosine may cause pancreatitis, at times severe, and, less frequently, peripheral neuropathy.
Side effects of zalcitabine are numbness and tingling in the extremities, painful swallowing, and abdominal pain. Zalcitabine is less likely than didanosine to cause pancreatitis, but more likely to cause peripheral neuropathy and oral or esophageal ulcerations.
Because current data do not suggest a clear-cut therapeutic benefit for either of these agents, it is appropriate for the clinician to base his or her choice at least in part on the medication's side effects profile.
For example, when considering the addition or substitution of another antiretroviral agent for zidovudine, zalcitabine should be offered to patients who may be at greater risk for pancreatitis or gastrointestinal symptoms. Didanosine should be offered to patients who may be at greater risk for peripheral neuropathy and/or oral ulcers.
In patients with preexisting pancreatitis or peripheral neuropathy, both didanosine and zalcitabine should be used with extreme caution.
Stavudine can cause numbness and tingling in the extremities, as well as peripheral neuropathy, liver function abnormalities, and pancreatitis. Because this drug was licensed relatively recently, clinical experience with it is more limited than with the other reverse transcriptase inhibitors. It is used in advanced HIV disease that is not responding to other antiretroviral therapy. Stavudine is not yet routinely used in combination therapy.
A new medication in the reverse transcriptase inhibitor class, 3TC, is currently in clinical trials and is available through compassionate release protocol. Preliminary data suggest that it may be effective when used in combination with zidovudine.
(TB screening is required by law in many AOD programs. For legal requirements regarding TB screening and treatment, see Chapter 7.)
Injecting drug users are at particularly high risk of TB. This observation preceded the AIDS epidemic but has been noted even more dramatically in recent years as a result of HIV infection. IDUs are the population group at highest risk of coinfection with Mycobacterium tuberculosis and HIV; TB incidence has increased alarmingly in this population and its contacts.
AOD abuse treatment programs are ideal sites for implementing effective screening, case finding, and supervised therapy and prophylaxis regimens for patients identified as having TB infection. Ideally, because of the growing importance of TB in the HIV epidemic, all AOD treatment programs should provide TB screening and prophylaxis onsite. If an AOD program does not offer onsite TB treatment, patients should be referred to a local health department.
TB may be transmitted to patients and staff at AOD treatment programs. In certain areas, there is a risk of transmission of multidrug-resistant (MDR) TB. Effective TB screening, surveillance, and followup programs are therefore critical.
NOTE: Under the 1993 Substance Abuse Prevention and Treatment Block Grants: Interim Final Rule, programs receiving block grant funds must either provide TB services onsite or make arrangements for patients to obtain them at another facility. (See summary of block grant interim regulations in Appendix B.)
TB screening. The standard technique for determining the presence of TB infection (which usually exists in latent form) is the tuberculin skin test. Typically, this test involves the intradermal injection of 0.1 ml of 5-TU purified protein derivative (PPD) of tuberculin, which is placed on the forearm and examined for induration (firmness or hardness of the skin at the injection site) 48 to 72 hours later. HIV-infected patients in AOD abuse treatment programs should be screened by PPD skin testing at least annually and possibly every 6 months, depending on the prevalence of TB or the risk of it among the population in the surrounding community. See Quick Reference Summary on TB screening, prophylaxis, and treatment.
It is likely that patients with HIV infection will not react in the normal manner to the tuberculin skin test because of diminished skin test reactivity resulting from immunosuppression. For this reason, the standard for a positive test of $10 mm of induration has been changed to $5 mm of induration for patients with known or suspected HIV infection.
There are several recent publications that clearly describe current guidelines for TB screening, including:
Treatment of Tuberculosis and Tuberculosis Infection in Adults and Children. (Bass et al., 1994.)
Tuberculosis and Human Immunodeficiency Virus Infection: Recommendations of the Advisory Committee for the Elimination of Tuberculosis (ACET). (CDC, 1989.)
Screening for Tuberculosis and Tuberculosis Infection in High Risk Populations and the Use of Preventive Therapy for Tuberculosis Infection in the U.S. Recommendations of the Advisory Committee for the Eliminations of Tuberculosis. (CDC, 1990.)
Some patients who are coinfected with HIV and TB will not respond at all to PPD skin testing; this false negative reaction is caused by a weakened immune system. For this reason, companion skin testing for cutaneous anergy is recommended for all patients with known or suspected HIV infection. Patients with cutaneous anergy are unable to react to any skin test antigens. (See Anergy Testing, below.)
TB prophylaxis. The standard anti-TB prophylaxis in patients with positive tuberculin tests is isoniazid (INH) 300 mg orally once daily, accompanied by 25 to 50 mg of vitamin B6. Other possible regimens include a twice-weekly regimen of INH (15 mg per kilogram of body weight, to a maximum of 900 mg), plus 25 to 50 mg of B6.
Ideally, these regimens should be administered in a supervised manner, i.e., the patient should be observed ingesting the medication. AOD treatment programs are ideally suited to providing such supervised therapy and have become increasingly important for both TB prophylaxis and therapy of active TB.
Recent increases in the incidence of MDR-TB have further highlighted the important role of directly observed therapy (CDC, 1992b). MDR-TB results in part from inadequate or partial completion of therapy and subsequent emergence of TB bacteria that are resistant to pharmacologic therapy. Directly observed therapy significantly reduces the risk of developing MDR-TB by ensuring that patients complete the course of treatment.
The lifetime risk that a PPD-positive, non-HIV-infected individual will develop active TB is approximately 10 percent. However, the 1-year risk of active TB in PPD-positive HIV-infected patients is 7 to 10 percent (Moreno et al., 1993;Selwyn et al., 1989). Given this significantly increased risk of active TB in HIV-infected individuals, a more aggressive treatment approach is justified in these patients.
For this reason, the standard practice of not prescribing INH to persons over age 35 (because of the danger of liver toxicity) is inappropriate for HIV-infected patients. INH prophylaxis should be offered to these patients with very few exceptions. Individuals receiving INH who have chronic alcoholic liver disease or active viral hepatitis should be closely monitored for liver toxicity.
The minimal necessary duration of INH prophylaxis in HIV-infected patients has not been established. INH prophylaxis should be offered to HIV-infected patients for at least 12 months; there is some indication that a period of less than 9 months may not be adequate. Whether it is necessary to continue beyond 12 months has not been determined; preliminary data suggest that 12 months may be sufficient.
In TB-endemic areas, some clinicians may opt to offer continued INH prophylaxis to patients as long as they are tolerating the regimen, even if they exceed the initial 12-month course. The management of HIV/TB coinfected patients should be undertaken with current information from infectious disease and public health experts. Patients known to be HIV-negative who have positive tuberculin skin tests should receive 6 months of INH prophylaxis.
Anergy testing. As discussed above, companion skin testing for cutaneous anergy is recommended for all patients with known or suspected HIV infection because patients with weakened immune systems may have false negative reactions to tuberculin testing. Anergy is most common at CD4+ counts below 200 but may be found even in patients with CD4+ counts above 500.
Anergy testing is usually most efficiently done at the same time as tuberculin testing. The preferred method of anergy testing uses several single intradermal antigens, for example, at least two of mumps, tetanus, and candida. The multiple-puncture tine test device (Multi-test-CMI, Merieux, Lyon) may be used, but separate single-antigen tests are preferable.
The antigen tests are read 48 to 72 hours after placement, at the same time the tuberculin skin test is read. Any induration at the site of the antigen test is considered indicative of the presence of a delayed type of hypersensitivity (DTH) skin test reactivity (i.e., that the patient's immune system is capable of responding to skin test antigens).
A negative reaction to all skin test antigens is considered indicative of cutaneous anergy. A negative PPD test in the presence of one or more reactive antigen tests is considered a true negative PPD. If all tests are negative, the patient is anergic; the PPD may be a false negative, and the patient should be evaluated for active TB. (See below.)
Management of anergic patients. Patients with cutaneous anergy should be evaluated for the presence of active TB with a chest x-ray and symptom screen (for example, persistent cough, fever, weight loss, night sweats). If any symptoms suggestive of TB are present, further diagnostic evaluation should be aggressively pursued.
Anergy not only indicates the possibility of a false-negative PPD, but also identifies patients at high risk for active TB. Several recent studies have documented that the risk of active TB may be as high as 5 to 10 percent per year among IDUs with cutaneous anergy and HIV infection -- similar to the risk in patients with HIV/TB coinfection (Selwyn et al., 1992b; Moreno et al., 1993). This risk may vary greatly by geographic region, depending on the background prevalence rate of TB in the population to which the AOD users belong (CDC, 1991b).
CDC recommends that 12 months of INH prophylaxis be considered for anergic HIV-infected patients in populations in which the estimated prevalence of M. tuberculosis infection is greater than 10 percent (CDC, 1991b). Most populations of IDUs in the northeastern United States, as well as in certain other regions, are in this category.
Medical care and drug treatment providers should consult actively with public health authorities to determine the estimated prevalence of M. tuberculosis infection in their population before considering whether INH prophylaxis is appropriate for all anergic HIV-infected patients. The effectiveness and minimal necessary duration of prophylaxis in anergic HIV-infected patients has not been determined.
Management of patients with active TB. Active TB may progress more rapidly in HIV-infected patients. Patients who are coughing should be evaluated as soon as possible for active TB. Facial tissues should be readily available at treatment programs and patients should be instructed to use them to cover their mouths and noses if they cough or sneeze. Medical staff of AOD abuse treatment programs should consider asking patients who are coughing persistently to wear masks until they have been fully evaluated for TB.
Patients with active TB should be hospitalized and isolated for approximately 2 weeks of pharmacotherapy. They may be seen in AOD treatment programs after 2 weeks of treatment, once they are determined to be no longer contagious, but they must continue daily, observed TB treatment. Patients with TB and those at high risk for contracting it should be housed in a facility with adequate ventilation and respiratory isolation capability.
For guidance on the control of TB, programs should consult CDC's TB control recommendations, published in the Federal Register (CDC, 1994b).
Current strategies for HIV care include the more widespread use of prophylactic regimens to help prevent specific opportunistic infections. As patients survive for longer periods with lower CD4+ counts, it will become increasingly important to develop additional prophylactic regimens for infections that occur at more advanced stages of immunosuppression. An excellent recent review summarized current practice regarding prophylaxis of opportunistic infections in HIV-infected patients (Gallant et al., 1994). (See Exhibit 3-10 and the following Quick Reference Summary box on prophylactic regimens).
Pneumocystis carinii pneumonia (PCP) prophylaxis. The first and most important opportunistic infection for which prophylactic regimens were developed was PCP, which was previously the most common opportunistic infection in patients with AIDS. The widespread use since the late 1980s of prophylaxis against PCP has resulted in a dramatic decrease in the incidence of this opportunistic infection during the last 5 years (Hoover et al., 1993).
The risk of PCP increases significantly when a patient's CD4+ count declines to about 200. It is recommended that all patients with CD4+ counts of 200 or below receive ongoing PCP prophylaxis. HIV-infected patients who have histories of oral candidiasis, recurrent bacterial infections, tuberculosis, and chronic constitutional symptoms should also be offered PCP prophylaxis regardless of their CD4+ cell levels because of their high risk of progression to AIDS.
In addition, anyone who has already had PCP, regardless of CD4+ cell count, should receive prophylaxis because of the high rate of recurrence of PCP (more than 30 percent within 1 year).
Trimethoprim-sulfamethoxazole (TMP-SMX) (Bactrim DS, Septra) is the most effective anti-PCP prophylaxis regimen (Gallant et al., 1994). The minimum effective dose of TMP-SMX is not known with certainty. A single daily dose of one double-strength tablet (160 mg of TMP and 800 mg of SMX) is most commonly prescribed.
A regimen of one double-strength tablet three times per week has also been recommended as adequate. Given concerns about adherence, however, many clinicians continue to recommend daily dosing. A daily single-strength tablet (80 mg of TMP and 400 mg of SMX) may also be effective (Schneider et al., 1992).
The incidence of PCP falls to less than 5 percent per year in patients who comply with this prophylactic regimen. Interesting preliminary data suggest that the incidence of both cerebral toxoplasmosis and pyogenic bacterial infections may also be decreased in persons taking TMP-SMX for PCP prophylaxis. This latter observation may be especially important for HIV-infected AOD users who are at high risk for bacterial pneumonia and endocarditis.
For patients unable to tolerate TMP-SMX, dapsone (a drug used in the treatment of leprosy) is a reasonable alternative. Because dapsone can cause hemolytic anemia in patients (especially people of African descent) who are deficient in the enzyme glucose 6-phosphate dehydrogenase (G6PD), patients must be screened for this deficiency before beginning therapy.
The minimal effective dose of dapsone is unknown; regimens of 50 mg per day, 100 mg per day, and 100 mg three times per week are common.
Aerosolized pentamidine, delivered through the RespirGard II nebulizer in a single dose of 300 mg per month, is another option for PCP prophylaxis. The advantages of aerosolized pentamidine are that it has little if any systemic toxicity, and it may be the only agent a patient can tolerate. However, it is clearly inferior to TMP-SMX.
Breakthrough rates of PCP in patients on pentamidine may exceed 15 percent a year. In addition, the syndrome of extrapulmonary pneumocystosis has been described in which patients show evidence of PCP infection outside the lung. These manifestations can be expected to occur more commonly in patients receiving only inhaled pentamidine rather than systemic prophylaxis with TMP-SMX or dapsone.
Pentamidine should be administered only in designated settings with adequate ventilation consistent with CDC standards. Not only can pentamidine administration produce bronchospasm and cough, but the induction of coughing has been associated with the transmission of TB in inadequately ventilated settings. Some AOD treatment programs offering onsite aerosolized pentamidine have used specially designed sputum induction and pentamidine administration booths equipped with strong exhaust systems and high-efficiency particulate air (HEPA) filters to decrease the risk of contamination.
Side effects. TMP-SMX as a single daily tablet is well tolerated, with a low incidence of side effects. However, patients with HIV infection have a higher risk of allergy to sulfonamides than other patient populations and need to be monitored for adverse effects. Side effects, which tend to be dose related, may include rash, leukopenia, nausea and vomiting, liver function abnormalities, and fever. Serious reactions such as Stevens-Johnson syndrome, mucous membrane ulceration, hepatitis, and serum sickness are infrequent but potentially serious.
Patients on dapsone may experience rash, gastrointestinal upset, and anemia. Less common side effects include mental status changes and peripheral neuropathy. Sulfa allergy is generally not a contraindication to dapsone. Many patients who have developed rashes on TMP-SMX are able to tolerate dapsone without adverse effects; however, they should be monitored as part of routine followup.
Pregnancy. The current standard of care is to offer a pregnant woman PCP prophylaxis if she would be so treated if not pregnant (for example, CD4+ count < 200, or preexisting HIV-related disease). Although the treatment's possible risks or benefits to the fetus are uncertain, it has become standard to use TMP-SMX until 36 weeks gestation and then change to aerosolized pentamidine to prevent neonatal exposure to sulfonamides (which can cause jaundice in the newborn).
Toxoplasmosis. Cerebral toxoplasmosis, another common opportunistic infection in patients with AIDS, occurs most commonly in people who have previously had a positive antitoxoplasma antibody test. Serologic testing for toxoplasma antibody is recommended as part of the basic primary care approach to HIV infection, in order to detect patients at high risk of development of this complication.
A positive antitoxoplasma antibody test is an indication to consider toxoplasmosis prophylaxis, especially in patients with CD4+ counts below 200 and/or a history of HIV symptomatic disease. Patients with a history of toxoplasmic encephalitis and other diseases from toxoplasmosis are maintained on chronic suppressive therapy with sulfadiazine and pyrimethamine plus folinic acid. Although not officially recommended, prophylaxis is appropriate for patients without prior disease who have latent infection with Toxoplasma gondii as indicated by a positive serum antibody test.
No specific regimens have been universally approved for prophylaxis against toxoplasmosis. It has been observed in several studies that anti-PCP prophylaxis with TMP-SMX may also offer protection against the development of toxoplasmosis. For patients who are unable to tolerate TMP-SMX, it has been suggested that dapsone plus pyrimethamine may provide effective prophylaxis against toxoplasmosis as well as against PCP (Girard et al., 1993).
Mycobacterium avium complex. Patients with AIDS are also at risk for infection with atypical mycobacteria, especially Mycobacterium avium complex (MAC). This is a late-stage complication of HIV disease that generally occurs in its disseminated form (for example, in the blood) only in patients with a CD4+ count of less than 50. As patients survive for longer periods with low CD4+ counts, prevention and treatment of this common complication will be increasingly important.
The rifampin-like drug rifabutin is approved for prophylaxis against disseminated MAC infection in patients with fewer than 100 CD4+ cells. At a dose of 300 mg per day, rifabutin was demonstrated in two clinical trials to protect against the development of bacteremia from MAC (Nightingale et al., 1993; CDC, 1993).
However, clinicians must be aware that rifabutin may cause adverse interactions with other HIV disease medications, including fluconazole and clarithromycin.
It is not known with certainty whether rifabutin, like rifampin, causes accelerated metabolism of methadone; as a result, caution should be exercised in prescribing rifabutin to methadone-maintained patients.
Because of the potential for adverse drug interactions with rifabutin, clinical approaches to MAC prophylaxis vary. Some clinicians opt to wait until the CD4+ count drops to 50 before initiating prophylaxis. Others choose not to pursue prophylaxis, using the rationale that the disease is generally treatable (although treatment usually requires the use of three medications, and prophylaxis only one) and that patients should not be unnecessarily exposed to drug toxicity.
Another possible rationale for not pursuing MAC prophylaxis is that the use of a rifampin-like drug may promote the emergence of rifampin-resistant M. tuberculosis, especially in TB-endemic areas. Active TB should be ruled out in all patients taking rifabutin.
Clarithromycin and azithromycin, the two new macrolide antibiotics that are useful in the treatment of disseminated MAC, may also have a role in MAC prophylaxis. As of early 1995, however, these drugs were still being studied in clinical trials for this indication. There is currently no official recommendation for their use as prophylactic agents.
Cryptococcosis. Cryptococcal meningitis is a relatively infrequent complication of HIV infection, although it is one of the more common AIDS-defining opportunistic infections of the central nervous system. The treatment of cryptococcal meningitis has been greatly aided in recent years by the introduction of new systemic triazole antifungal medications such as fluconazole and itraconazole. These agents have made it possible to shorten the initial course of intravenous therapy with amphotericin B for crytococcosis and certain other systemic fungal infections (for example, histoplasmosis) and have allowed chronic suppressive therapy with oral agents that do not require chronic intravenous administration.
Although it has been observed that patients receiving fluconazole may be less likely to develop cryptococcosis, it has been suggested that because cryptococcosis is not a common infection (occurring in fewer than 10 percent of patients with AIDS), routine prophylaxis is not cost effective.
There is a risk that routine prophylaxis of cryptococcosis would promote the development of resistant organisms, including resistant candida and other fungal species. In addition, in parts of the country where histoplasmosis and coccidioidomycosis are more common fungal complications of AIDS, the use of fluconazole has not been associated with decreased risk of occurrence of these infections.
Herpes simplex virus and cytomegalovirus. HIV-infected patients with recurrent genital HSV infection (and, less commonly, recurrent infection at other sites) should receive chronic prophylaxis with acyclovir (generally from 800 to 2,400 mg daily in two or three doses), as might be done in patients without HIV infection.
The likelihood of recurrent HSV infection increases with a declining CD4+ count. There is no strict threshold for the initiation of prophylaxis. Recent evidence suggests that acyclovir taken together with antiretroviral therapy may confer a survival benefit in late-stage AIDS patients (Stein et al., 1994;Youle et al., 1994).
There has been much recent interest in potential prophylactic agents against cytomegalovirus (CMV), which, like MAC, has been an increasingly common finding in patients surviving for longer periods of time at very low CD4+ counts. CMV most commonly causes retinitis, which can lead to blindness if untreated, and may also cause gastrointestinal, adrenal, pulmonary, and other systemic disease. At present, however, there are no clinically available options for primary prevention of this complication.
Currently, the only treatment options for CMV are intravenous gancyclovir or intravenous foscarnet; these agents must be continued indefinitely as suppressive therapy following initial treatment. Clinical trials valacyclovir, are under way an acyclovir-like oral agent that may offer some prophylactic benefit against the development of CMV disease, as well as an oral form of gancyclovir, which has shown promise in preliminary trials as a prophylactic against CMV.
AOD users are at risk for a somewhat different spectrum of HIV-related disease than other HIV-infected populations. The following box summarizes the clinical spectrum of HIV-related disease and complications of drug use. The following description of conditions that clinicians are likely to encounter in treating an HIV-infected AOD abuse population is adapted from two articles describing treatment for this population (Selwyn and O'Connor, 1992;O'Connor et al., 1994).
Bacterial Infections. Bacterial pneumonia and sepsis were clearly described in IDUs before the AIDS epidemic, but they have been found to occur more frequently in HIV-infected AOD users. Bacterial pneumonia in this population is most often caused by Streptococcus pneumonia and Hemophilus influenzae. Both bacterial pneumonia and related bacteremia in HIV-infected AOD abusers tend to occur first in the earlier stages of immunosuppression and to be predictors of subsequent HIV-related illness in previously asymptomatic patients.
CDC currently recommends offering the pneumococcal polysaccharide vaccine to all HIV-infected patients. This vaccine is of questionable efficacy in patients with severely weakened immune systems, but it has been found to provide moderate immunity when given in the earlier stages of HIV infection. H. influenza vaccine may also be considered in HIV-infected patients, who are at increased risk for H. influenzae pneumonia.
Bacterial endocarditis is a well-recognized complication of injection drug use. Several studies have suggested that HIV infection may aggravate the frequency and severity of endocarditis, while others have shown a similar course in HIV-seropositive and HIV-seronegative drug uses with endocarditis. Active IDUs are also at risk for a variety of serious bacterial infections involving the skin, soft tissues, bones, joints, central and peripheral nervous systems, and other anatomical sites. Proper needle hygiene and skin disinfection prior to drug injection may help prevent some of these complications of nonsterile needle use.
Tuberculosis. (See above, pages 39-42.)
Sexually transmitted diseases. STDs are common in AOD abusers, particularly among women involved in commercial sex work or the exchange of sex for drugs. Users of cocaine (especially "crack") have also been found to be at increased risk of STDs.
Baseline assessment should include taking the patient's history of STDs and involvement in sex-for-sale or sex-for-drugs transactions. Inspection for genital and perianal lesions should be part of the baseline physical examination. Serologic testing for syphilis (including both treponomal and nontreponomal tests, for example, VDRL and FTA-Abs) should be included in the initial laboratory testing screen.
Female AOD users should be offered a complete pelvic examination and testing for gonorrhea, chlamydia, and herpes simplex virus (as well as Pap smears at least annually because of the women's increased risk of cervical cancer). (See section on Women's Health Issues below.)
Incidence of syphilis. Between 1985 and 1990, the reported incidence of primary and secondary syphilis in the United States increased by more than 75 percent, with more than 50,000 cases being reported. A large proportion of the increase was attributable to substance use, especially the use of crack cocaine.
Treatment of syphilis. HIV-infected patients with primary and secondary syphilis should receive at least one intramuscular injection of benzathine penicillin (at least 2.4 million units). Multiple weekly doses of benzathine penicillin (up to a total of 7.2 million units), or treatment with supplemental antibiotics (amoxicillin or ampicillin with or without probenecid) may be advisable in some cases.
CDC recommends that, prior to treatment, HIV-infected patients with latent syphilis undergo lumbar puncture and cerebrospinal fluid (CSF) examination to rule out neurosyphilis. Patients whose CSF test results are normal should receive three weekly intramuscular injections of benzathine penicillin (2.4 million units). Those with evidence of neurosyphilis should receive a more prolonged course of 10 to 14 days of intravenous penicillin.
Clinicians treating HIV-infected AOD abusers with latent syphilis may encounter practical difficulties in trying routinely to follow the recommendation above for lumbar puncture. It is logistically difficult to perform lumbar puncture in the setting of an AOD treatment program, and asymptomatic patients are often unwilling to undergo the procedure.
Some alternative approaches, while not formally recommended, may be more practical for treatment of an HIV-infected AOD abuse population:
Treat all latent-syphilis HIV-infected patients
Reserve lumbar puncture and CSF examination for patients who have neurological complications or whose followup serologic tests do not indicate a clear response to antibiotic therapy.
Have a low threshold to refer patients aggressively for further diagnostic workup or treatment as indicated.
For further guidance on treatment of STDs, please refer to Sexually Transmitted Diseases Treatment Guidelines (CDC, 1993e).
Hepatitis. Evidence of infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) has been found in more than two-thirds of long-term IDUs (Donahue et al., 1991; Esteban et al., 1989; Stimmel et al., 1975). Chronic AOD users are also at increased risk for infection with hepatitis A virus (HAV) and hepatitis delta virus (HDV), which coexists with HBV. Underlying liver disease in AOD abusers may complicate the diagnosis of liver-function abnormalities and aggravate the liver toxicity of medications used to treat HIV infection, including TMP-SMX, pentamidine, dapsone, rifampin, INH, didanosine, and zalcitabine (O'Connor et al., 1994).
There is no consistent evidence that coexisting chronic hepatitis B infection adversely affects the course of HIV disease or, conversely, that HIV disease adversely affects coexisting HBV infection. However, individuals who are coinfected with HIV and HBV may have higher blood levels of HBV than individuals who are not HIV infected. Consequently, these coinfected individuals may be at higher risk of transmitting HBV infection.
CDC recommends that all susceptible HIV-infected individuals and the healthcare workers who provide their care should receive the HBV vaccine. A complete HBV serologic profile should be part of the baseline assessment of all AOD abusers with or at risk for HIV infection; patients found to be negative for HBV antibody markers should be considered eligible for HBV vaccine.
See Quick Reference Summary on the screening and prevention of infectious disease.
Nervous system disease. Clinicians caring for HIV-infected patients must frequently assess patients for altered mental status and other neurologic and neuropsychiatric syndromes. Differential diagnosis in such patients may include HIV-related dementia or encephalopathy, specific opportunistic infections affecting the central nervous system, metabolic or toxic encephalopathy, and the effects of substance abuse.
Underlying neurologic conditions associated with AOD use can obscure or complicate the diagnosis of the varied causes of peripheral nervous system disease in HIV-infected patients.
HTLV-I and HTLV-II. These retroviruses are "cousins" of HIV. Human T-lymphotropic retrovirus type 1 (HTLV-I) has been associated with adult T-cell leukemia/lymphoma and with certain chronic degenerative neurologic diseases. HTLV-II is less clearly associated with specific disease outcomes.
In the United States, infection with HTLV-I and HTLV-II is concentrated among IDUs. Seroprevalence studies in the mid-1980s found that more than one-third of AOD users in selected groups sampled in the New York metropolitan area and in the southeastern United States were infected with HTLV-I and/or II. (Current antibody tests cannot readily distinguish between the two viruses.)
Recent data suggest that most AOD users who are coinfected with HIV and HTLV-I and/or II in fact have HTLV-II (Khabazz et al., 1992). In at least one study, HTLV-II coinfection was associated with rapid progression of HIV disease in AOD users infected with both viruses (Page et al., 1991).
Clinicians caring for HIV-infected AOD abusers should suspect coexisting HTLV-I or HTLV-II infection and consider serologic testing in patients with degenerative neurologic disease, T-cell leukemias, or rapidly progressing HIV disease.
Malignancies. Three types of cancer -- Kaposi's sarcoma, malignant lymphoma including different subtypes, and cervical cancer -- are considered AIDS-defining conditions under the classification system for HIV infection and AIDS established by CDC in 1993.
HIV-infected AOD abusers are at relatively low risk for Kaposi's sarcoma; however, malignant lymphomas have been documented in this population. Persistent generalized lymphadenopathy is common in HIV-infected patients and palpable lymphadenopathy is frequently seen in IDUs. Nevertheless, the presence of large (>2 cm), firm, tender, or rapidly growing lymph nodes in an HIV-infected IDU patient should always prompt further diagnostic evaluation.
Women who are current or former AOD users comprise approximately 50 percent of AIDS cases in women to date in the United States. Clinicians treating AOD-abusing women should therefore be particularly alert to the possibility of cervical cancer in this population.
In addition to these AIDS-defining cancers, other malignancies have been found to occur with greater
frequency in HIV-infected AOD abusers. These non-AIDS-defining cancers (reported in several case series and one population-based study) have included solid tumors of the lung, head and neck, and gastrointestinal tract. Lung tumors are the most common (O'Connor et al., 1994).
Although such malignancies are rare, and HIV infection as their cause is unproven, primary care providers should be aware that HIV-infected IDUs who also smoke and drink alcohol heavily may be at increased risk for these cancers.
The following is condensed from an article on preventive healthcare by Hecht and Jewett (1993).
CDC recommends that HIV infection be considered an indication for pneumococcal vaccination because of the markedly increased risk of pneumococcal pneumonia among HIV-infected patients. Vaccination against H. influenzae type B should also be considered because HIV-infected individuals, particularly IDUs, are at increased risk for H. influenzae pneumonia.
CDC recommends the influenza vaccine for all HIV-infected persons. Vaccination for influenza is potentially useful for two reasons:
HIV-infected patients are known to be at increased risk of pulmonary infection with bacteria that commonly complicate influenza.
Because symptoms of influenza may mimic those of opportunistic infections, a reduction in the incidence of influenza may prevent unnecessary diagnostic evaluations for other HIV-related conditions.
Persons providing care of HIV-infected individuals should also be advised to be vaccinated against influenza.
CDC recommends that all susceptible HIV-infected individuals and the healthcare workers who provide their care should receive the HBV vaccine. Patients with HIV infection, if they have not already been exposed to HBV, are at high risk of acquiring it. HIV-infected individuals are at considerably greater risk than non-HIV-infected individuals of becoming chronic HBV carriers. Further, HIV-infected HBV carriers may be more infectious because they are likely to have higher blood levels of HBV. (See information under Laboratory Tests on pp. 31-34.)
All of the above-mentioned vaccines are more effective when administered early in the course of HIV infection. There is little evidence that they are harmful to HIV-infected persons.
Other immunizations. Few data exist on the safety or efficacy of vaccination of HIV-infected adults for diphtheria, tetanus, mumps, rubella, polio, and measles. Inactivated polio, diphtheria, and tetanus vaccines are likely to be safe. Because these infections may cause illness in patients with suppressed immune systems, vaccination appears warranted according to standard guidelines for their use in non-HIV-infected adults.
Vaccination with the live, attenuated mumps, rubella, and measles vaccines may pose a greater risk to HIV-infected persons, and the benefit is less certain. However, these vaccines are routinely used in HIV-infected children whose immune systems are not suppressed, and in recent years, the measles vaccine has been safely given to HIV-infected adults during local measles epidemics. Measles vaccination should be considered for HIV-infected AOD abusers at risk of contracting measles. (See Quick Reference Summary, Immunizations in HIV-Infected Patients.)
Primary care providers should be aware that, in general, the incidence of gynecological disorders is likely to be higher among female substance abusers than among non-AOD-abusing women. Some disorders (such as STDs) result directly or indirectly from substance use, while others may result from lifestyle factors that influence the overall health status of women in this population, such as poverty and lack of regular medical care.
Candidiasis. HIV-infected women may have more frequent and severe vaginal candidiasis than women who are HIV negative. The risk of severe or refractory vaginal candidiasis increases with a declining CD4+ count. Less severe cases of candidiasis should be treated with antifungal creams or suppositories. Severe or chronic cases may require treatment with systemic fluconazole.
Cervical abnormalities. HIV-infected women are at increased risk for cervical dysplasia and possible invasive cervical cancer. Human papillomavirus (HPV) infection is significant in HIV-infected women because of its association with cervical dysplasia and cancer. Since 1993, invasive cervical cancer has been considered an AIDS-defining condition. Women who are current or former AOD users comprise approximately 50 percent of AIDS cases in women to date in the United States. Clinicians treating AOD-abusing women should therefore be particularly alert to the possibility of cervical cancer in this population.
HIV-infected women should receive Pap tests at least annually. Every 6 months, Pap tests should be considered in HIV-infected women at particularly high risk for cervical cancer, such as women with low CD4+ counts and women who smoke. Facilities treating HIV- infected women must either provide Pap smears and gynecologic followup on site or have contractual arrangements for the provision of these services. The efficacy of routine colposcopy as an additional means of screening high-risk HIV-infected women for cervical pathology is under evaluation.
STDs. Treatment of sexually transmitted disease in AOD patients was discussed on page 47. For further guidance on treatment of STDs, please refer to Sexually Transmitted Disease Treatment Guidelines (CDC, 1993e).
The HIV status of an infant born to an HIV-infected mother may not be known with certainty for up to 18 months after birth. All infants will initially have a positive HIV antibody test because of the presence of maternal antibodies in their blood. However, only 20 to 30 percent of infants will be found on followup to be HIV-infected. New diagnostic techniques may soon be able to diagnose HIV infection in infants earlier than is currently possible.
This information must be shared with the HIV-infected pregnant woman; her options should be presented in a nondirective fashion that empowers her to make her own decision about whether to continue her pregnancy with optimal prenatal care or seek a termination.
NOTE: The 1993 Substance Abuse Prevention and Treatment Block Grants: Interim Final Rule requires AOD programs to link pregnant patients with prenatal services. (See summary of block grant interim regulations in Appendix B.)
Zidovudine therapy in pregnancy. Recent data indicate that zidovudine therapy may have a key role in preventing perinatal transmission of HIV from mothers to infants. A double-blind, placebo-controlled trial conducted by the National Institutes of Health AIDS Clinical Trials Group (ACTG), in collaboration with French researchers, found that only 8 percent of infants born to women treated with zidovudine were infected with HIV, compared with 26 percent of infants born to women treated with a placebo (CDC, 1994).
Women entering the ACTG study were between 14 and 34 weeks pregnant and had CD4+ cell counts above 200 (median CD4+ counts were approximately 550 in both treatment and placebo groups). Preliminary results of a second study found a similar protective effect for zidovudine among infants born to women with CD4+ counts below 200 (Boyer et al., 1994).
Participants in the ACTG study received an average of 12 weeks of therapy (200 mg zidovudine 3 times a day). Their newborn babies also received zidovudine during an initial postnatal followup period. Zidovudine did not appear to result in significant toxicity or differences in obstetrical outcomes between the treatment and placebo groups.
While the long-term effects on fetuses and infants of intrauterine exposure to zidovudine are unknown, these data represent the first evidence that the medication can reduce the risk of perinatal transmission of HIV. CDC now recommends that pregnant HIV-infected women receive zidovudine therapy. Given the large number of childbearing women among patients in substance abuse treatment programs, these data indicate an immediate need for expanded HIV counseling, testing, and education for women who are pregnant or likely to become pregnant.
HIV-infected AOD-abusing women are frequently the sole care providers for young children. Issues such as child care and transportation often must be addressed to bring these women into medical care and ensure that they continue to receive care. The children of HIV-infected women may be HIV-infected themselves and may have complex care needs. It is important that their care be coordinated with that of their mothers.
For uninfected children of HIV-infected women, decisions concerning custody and guardianship may be necessary. (See box, Chapter 5 on Custody of Children of HIV-Infected Parents.)
Because women AOD abusers are at higher than average risk of physical and sexual abuse, healthcare workers should inquire directly about these issues. Partner notification of a woman's HIV status needs to be considered sensitively, and healthcare workers should be aware that women may fear victimization by a sexual partner. (See section on Partner Notification in Chapter 7.)
The box on the next page provides a Quick Reference Summary of health issues for HIV-infected women with AOD abuse problems.
AOD abuse treatment personnel must be aware of the special nutritional needs of HIV-infected AOD abuse patients. They should also be familiar with guidelines concerning nutritional supplements and with interventions to address the causes of inadequate food consumption. (See Exhibit 3-11 for a summary of factors that must be considered in relation to the patient's food consumption.) Patients who are losing weight and for whom nutritional supplements are inadequate or ineffective should be referred to an HIV specialist (Gorbach et al., 1993). Clinicians must recognize that the overwhelming concern of many active AOD abusers may be obtaining substances of abuse rather than food. In an AOD abuser infected with HIV, this priority can exacerbate nutritional problems.
Managing acute and chronic pain in HIV-infected AOD abuse patients can be a challenging clinical problem (Selwyn and O'Connor, 1992). Although providers may have well-founded concerns about potential drug-seeking behavior, these concerns may interfere with clinical judgment about the appropriateness of narcotic analgesics. Like other patients, AOD abusers are often undertreated for acute pain. Medication for pain control, including narcotics, should never be withheld merely because a patient has a history of AOD abuse. (See Quick Reference Summary on pain management in HIV-infected AOD abuse patients.)
As in all patients with pain, the provider's primary goal is to maximize comfort while minimizing side effects. Local measures (rest, heat, ice, analgesic rubs) should be used as a first line of pain treatment where appropriate. If these measures fail to adequately control the pain, a systematized pharmacologic approach is recommended. Initially, over-the-counter medications such as aspirin, acetaminophen, and nonsteroidal anti-inflammatory agents should be used, with dosages increased as needed.
If these medications prove inadequate for of their tolerance for narcotics, opiate addicts generally require higher doses of narcotic analgesia and more frequent dosing intervals for effective pain control. This is especially true for patients maintained on methadone.
Agents used for persistent neuropathic pain include anticonvulsants (phenytoin, carbamazepine); tricyclic antidepressants (amitriptyline, desipramine);and clonazepam (with caution regarding its abuse potential). These agents may be used alone or in combination with other analgesics. Acupuncture may be particularly helpful in some cases of neuropathic pain.
The treatment plan and the reason for using narcotics for pain control must be clear to both provider and patient when analgesic therapy for acute pain is initiated. It is important not only that patients feel their pain is taken seriously, but also that narcotic use not be extended beyond a time-limited period required for analgesia. (An exception to this general principal may be evaluated in late-stage patients with AIDS who may have chronic, severe pain syndromes requiring ongoing analgesia).
Chronic pain management in AOD abuse patients is most effective in a setting of close primary care followup and coordination of a treatment plan with substance abuse treatment professionals. Pain management specialists should be consulted as needed to examine alternative management strategies (Selwyn and O'Connor, 1992).
Reducing the risk of medication abuse. Setting clear limits and devising a consistent treatment plan help reduce the risk of medication abuse by AOD-abusing patients. The following strategies are recommended:
Designate one care provider to dispense prescriptions for controlled drugs.
Dispense limited amounts of controlled drugs (e.g., 1 week's supply or less).
Advise patients that lost or stolen prescriptions will not be replaced.
(See also Abuse of Psychiatric Medications, Chapter 4)
Special considerations in methadone-maintained patients. This above-mentioned agents may be used in patients maintained on methadone, but providers should be aware of their pharmacokinetic effects. (See next section and quick summary of pharmacologic interactions, above.) Attempting to manage pain in methadone-maintained patients by increasing their daily dose of methadone is a common error. Instead, if narcotic analgesics are indicated, providers should continue the patient's usual methadone dose and add a shorter-acting narcotic for pain control.
Pentazocine and other mixed opiate agonist-antagonists should not be used for analgesia in methadone-maintained patients because they may precipitate withdrawal.
HIV infection does not change the indications for medication to treat AOD abuse. The most common medications used to treat substance abuse are methadone, disulfiram, and naltrexone. In addition, benzodiazepines,barbiturates,clonidine hydrochloride, and other medications are commonly used in detoxification. These medications can be used in HIV-infected AOD abuse patients the same way they are used in noninfected patients. The detoxification process need not be altered by the presence of HIV infection.
Interactions with methadone. The best-documented interaction between medications for substance abuse and those for HIV infection or related conditions is methadone/rifampin, used to treat tuberculosis or, less commonly, M. avium complex (Kreek et al., 1976). Rifampin causes more rapid breakdown of methadone in the liver and more rapid elimination of methadone in general, lowering the plasma methadone level. This results in the rapid onset of classic opioid withdrawal symptoms, usually within several days of rifampin initiation.
Dispense limited amounts of controlled drugs (for example, 1 week's supply or less).
Advise patients that lost or stolen prescriptions will not be replaced. (See section, Abuse of Psychiatric Medications, in Chapter 4.)
Special considerations in methadone-maintained patients. The above-mentioned agents may be used in patients maintained on methadone, but providers should be aware of their pharmacokinetic effects. (See next section and Quick Reference Summary of pharmacologic interactions.) Attempting to manage pain in methadone-maintained patients by increasing their daily dose of methadone is a common error. Instead, if narcotic analgesics are indicated, providers should continue the patient's usual methadone dose and add a shorter-acting narcotic for pain control.
Pentazocine and other mixed opiate agonist-antagonists should not be used for analgesia in methadone-maintained patients because they may precipitate withdrawal.
Increasing patients' daily methadone doses will prevent this outcome. Typically, the dosage is increased by 10 mg every 1 to 2 days, beginning on the day rifampin is started and increasing as needed to prevent symptoms of opioid withdrawal, titrated to prevent oversedation. It is often necessary to continue this pattern until the dosage is at least 50 percent greater than the original daily dose.
Phenytoin and phenobarbital have a similar but less dramatic effect on plasma methadone levels, causing opioid withdrawal symptoms over a period of days to weeks (Tong et al., 1981). Methadone dosage increases may be necessary but usually need not be as great or as rapid as is necessary when patients are given rifampin.
When therapy with rifampin or phenytoin is discontinued, methadone doses should in most cases gradually be lowered to avoid oversedation. Patients will usually arrive at a final stable dose higher than their original dosage level before the other medications were introduced (Selwyn and O'Connor, 1992).
Rifabutin is a medication structurally related to rifampin and is frequently used for prophylaxis and treatment of M. avium complex in HIV-infected patients (Nightingale et al., 1993). Rifabutin may have a similar pharmacologic interaction with opioids. One small study found that, unlike rifampin, rifabutin did not predictably result in accelerated metabolism or elimination of methadone in chronic opiate addicts (Sawyer et al., 1993). Definitive data are lacking, however, and clinicians should consider this possibility.
Interactions with zidovudine. No clinically significant interactions have been found between methadone or disulfiram and zidovudine. One study suggested, however, that elimination of zidovudine may be decreased in methadone-maintained patients compared with a control group not receiving methadone (Schwartz et al., 1992). However, this study found no evidence of worse clinical toxicity from zidovudine in the methadone-maintained group. Several studies confirm that zidovudine is well-tolerated in HIV-infected opiate addicts (Broers, 1994;Samet et al., 1992a;Samuels et al., 1990;Selwyn et al., 1989;Selwyn et al., 1993).
Interactions with other antiretroviral agents. Little information is currently available about the toxicity profiles of the newer HIV antiretroviral agents (didanosine,zalcitabine, and stavudine) in AOD abusers. Because of the high risk of underlying alcoholic liver disease, hepatitis B and/or C virus infection, and pancreatitis in AOD abusers, it is important that patients taking these newer agents be closely monitored and evaluated for additive toxicity (O'Connor et al., 1994).
Good physician-patient relationships can foster patient participation in clinical trials. Ongoing efforts are needed to educate patients about the utility of clinical trials and to alleviate their longstanding suspicion of the medical profession. Clinicians must be aware that HIV-infected AOD abusers who are recovering in abstinence-based treatment programs may be reluctant to participate in clinical trials of nonapproved medications because such participation reminds them of taking illicit drugs. Recovering AOD abusers who are involved in abstinence-based treatment programs may not wish to take drugs of any kind.
Specific efforts should be made to incorporate more AOD abuse patients, women, and minorities into HIV clinical trials. All of these groups are currently underrepresented. Medical staff of AOD programs also should be educated about the importance of clinical trials.
To avoid conflicts of interest, it is recommended that, as far as possible, the clinician responsible for the clinical trial not be the patient's primary care provider. When a patient enters a trial, mechanisms for followup of results must be established so that this information is available to AOD abuse treatment staff.
HIV-infected AOD abuse patients are likely to experience crisis points in their HIV treatment that place them at increased risk for drug-seeking behavior or relapse. Events that may trigger such a crisis include:
Confirmation of positive HIV status
A drop in the CD4+ count
The illness or death of a friend or loved one
A bout of PCP or other serious HIV-related illness.
Patients facing crises need close monitoring and enhanced intervention strategies. An increased level of contact with established support systems is essential during these stressful times to avoid or mediate relapse. For example, when a patient is hospitalized for HIV treatment, it may be helpful to arrange visits from staff of the patient's AOD abuse treatment program.
When crises occur, patients may demand higher doses of psychotropic medication. Medical providers should anticipate such crises and engage their HIV-infected patients in appropriate relapse prevention planning.
When disclosing diagnostic test results, clinicians must be sensitive to patients' counseling needs. For example, it may be helpful to alert counseling staff when a patient is told that his or her CD4+ count has fallen. Clinics should refrain from disclosing HIV antibody test results on Fridays unless staff are available on weekends to deal with patients' anxiety. (See section on HIV Disease and Risk of Relapse in Chapter 4.)
In the face of a life-threatening, chronic illness in which optimal care is still undefined, many patients will seek out unapproved medications and alternative therapies. Care providers must be aware that many HIV-infected patients may not be adhering to prescribed regimens or may be taking additional prescribed or nonprescribed medications in an inappropriate or non-FDA-approved manner. Patients may also be involved in the use of alternative or complementary therapies (for example, acupuncture, meditation, and vitamin and herbal dietary supplements).
Clinicians have a responsibility to find out, in a nonjudgmental manner, what alternative or unapproved therapies patients are using and to obtain as much information as possible about these treatment modalities. This information should be shared with patients, emphasizing that the risks and benefits of these therapies cannot always be predicted.
Unsupervised antibiotic use, in particular, can complicate the diagnosis and treatment of bacterial infections in HIV-infected AOD abuse patients. Clinicians should inquire specifically about unsupervised antibiotic use because patients may not consider the information relevant to their medication or drug use histories unless they are asked about it (Selwyn and O'Connor, 1992).
The use of alternative or adjunctive therapies varies according to locale and cultural characteristics. Their use is generally less widespread among HIV-infected AOD abusers than among non-AOD-abusing HIV-positive individuals. Data support the use of some alternative therapies, but others have no proven benefits. Unless a therapy is known to be harmful, however, patients need not be discouraged from trying it. Certain alternative therapies (for example, acupuncture, meditation, and herbal teas) may actually play a very useful role in decreasing patients' reliance on or need for controlled substances, narcotic analgesics, sleeping medication, and so forth.
Clinicians should assess drug-using patients' compliance and responsibility in handling prescribed medications. Medications should be dispensed consistently, with clear limits set on drug-seeking behaviors (Selwyn and O'Connor, 1992). As noted above, in the discussion of pain management, special controls need to be placed on the prescription of medications with high abuse potential (for example, narcotics, benzodiazapines), including explicit rules that medications reported lost or stolen will not be replaced, only small numbers of pills will be dispensed at one time, prescription refills will only be obtainable through one designated care provider, and so forth.
Exhibit 3-12 lists uses of alternative therapies and unapproved medications of which clinicians caring for HIV-infected AOD abusers should be aware.
The AIDS epidemic poses a number of challenges for infection control policy and practice in substance abuse treatment programs. Effective institutional infection control is more relevant for preventing the transmission of TB than for preventing the spread of HIV, although the latter often has received a greater amount of attention.
Adherence to universal precautions for exposure to blood and body fluids -- as recommended by CDC, the National Institute of Occupational Safety and Health (NIOSH), and a wide range of other associations and organizations -- has been well established as the necessary standard of practice for all settings in which exposure to blood and body fluids is a potential hazard. Substance abuse treatment programs should apply the same standards of universal precautions that are in place in hospitals and other healthcare facilities (CDC, 1988). (See Exhibit 3-13.)
Programs should seek guidance on adhering to universal precautions from local public health authorities or infection control staff of an affiliated institution. In settings such as freestanding community-based treatment programs, safe disposal of infectious wastes may require a deviation from standard waste disposal practices.
The transmission of HIV infection is highly unlikely within institutions such as healthcare facilities, residential facilities, correctional facilities, residences, and substance abuse treatment programs when universal precautions are observed. By contrast, transmission of TB (including MDR-TB) has been proven to occur in all of these settings. Both epidemiologic and molecular genetic studies have documented the transmission of TB among immunosuppressed contacts within these environments, with high attack rates and high mortality rates, especially for MDR-TB (Daley et al., 1992;Fischl et al., 1992b;CDC, 1991a). TB infection control precautions should be developed with the guidance of infection control experts from affiliated institutions or public health agencies. (See Exhibit 3-14.)
As noted in the introduction to this chapter, many barriers prevent HIV-infected AOD abusers from receiving appropriate, timely medical care. According to one study, HIV-infected IDUs tend to delay seeking treatment, but once in treatment their compliance is no worse than that of other HIV-infected patients (Broers et al., 1994). Another study showed that patients' belief in the efficacy of zidovudine therapy is positively associated with adherence to treatment (Samet et al., 1992a). This finding underscores the need to educate patients and include them in all aspects of the treatment process.
Primary care providers need to be aware that a patient's relapse into AOD use may result in noncompliance with medical care. It is important that linkages be maintained between primary care and substance abuse treatment providers so that primary care providers are aware of such relapses when they occur.
Techniques to aid compliance. Techniques developed for use in geriatric psychiatry may be helpful in achieving better compliance among HIV-infected patients. These methods include:
Repetition of instructions
Written protocols
Support persons who reinforce the importance of keeping appointments and adhering to medication regimens
Use of a timing device to ensure that medications are taken at the proper time
Existing indications for supervised therapy that are already part of AOD abuse treatment need not be changed solely because of HIV infection. The need for supervision becomes more critical, however, with the additional diagnosis of TB in an HIV-infected AOD abuse patient. The possible emergence of MDR-TB in HIV-infected patients presents additional risks and complications. Close monitoring (directly observed therapy) of TB patients is necessary to prevent the development of MDR-TB.
To improve patient adherence to medical care, AOD abuse treatment programs must enhance their ability to provide supervised therapy. This supervision is especially important for patients with TB, but it is also a significant issue for those patients receiving antiretroviral and PCP prophylactic regimens but who have difficulty following prescribed regimens because of problems such as homelessness, cognitive impairment, or lack of health insurance or money to obtain medications.
The dispensing of TB medications along with methadone at a methadone treatment program is an example of enhanced supervised therapy.
Medications such as prophylactic antibiotics may also be given on a daily observed basis for patients with cognitive impairment or disorganized lifestyles; this supervision is particularly useful for medications that can be given only once daily or less (for example, TMX-SMX, fluconazole, and dapsone). AOD abuse treatment programs, because of their relatively intense interaction with patients, are in a unique position to help deliver such medication-related services. Different models for supervised therapy can be effective and should be developed for specific AOD treatment settings.
Adherence to medical care means more than simply taking medications as prescribed. The foremost challenge in providing HIV and AOD abuse treatment is engaging patients and empowering them to be active participants in their own care. Many HIV-infected AOD abuse patients may be deeply distrustful of medical providers. Some will refuse or resist treatment for fear that their HIV status will be disclosed.
Strict observance of patient confidentiality is an essential element of creating an atmosphere of trust in which patients can make the choices that are best for them. Encouraging patients to discuss their fears can help build trust between patients and providers. Patient education facilitates patient engagement and empowerment, and empowerment results in better adherence to medical care.
The following list of elements of a comprehensive patient education program is adapted from HIV-1 Guidelines for Chemical Dependency Treatment and Care Programs in Minnesota (Minnesota Department of Human Services, 1992.) All AOD abuse patients, whether HIV-infected or not, should receive education about:
The fundamentals of HIV and AIDS
Strategies for personal risk reduction
Relevant treatment program policies regarding HIV
Confidentiality rules and expectations
Benefits of HIV antibody testing
Overview of local HIV resources, including hotlines.
Patients who are HIV infected, whether they are symptomatic or not, should receive education about:
Their disease status, prognosis, and treatment options
Available medical and social service resources and entitlements and how to obtain them.
Linkages with other patients facing similar problems through support groups can promote empowerment by helping individuals feel less isolated and overwhelmed by their problems. Specific strategies for empowering and engaging patients may include:
Holding support group meetings at the AOD treatment facility
Offering educational sessions for HIV-positive AOD abusers in HIV and AOD treatment settings.
Most primary care services for HIV patients are provided within established AOD abuse treatment systems. It is crucial, therefore, that AOD abuse treatment professionals understand HIV-related issues and integrate them into existing services. Cross-training, consultation, referral, and mutual inservice training agreements between the staffs of HIV primary care treatment programs and AOD treatment centers can help achieve this integration.
Under the 1993 substance abuse block grant interim rule, employees of AOD treatment services must receive continuing education; education about HIV meets this requirement. (See summary of block grant interim rule in Appendix B.)
Healthcare staff at all levels who work with AOD abuse patients -- from administrators to maintenance staff handling infected waste -- need education about HIV-related issues. The following list of elements of a comprehensive HIV education program for AOD program staff is adapted from HIV-1 Guidelines for Chemical Dependency Treatment and Care Programs in Minnesota (Minnesota Department of Human Services, 1992:
Fundamentals of HIV and AIDS
Strategies for personal risk reduction
Infection control in the workplace
Harm reduction and abstinence models of care
Overview of laws regarding confidentiality and access to services
Program policies and procedures regarding HIV
Overview of resources available to HIV-infected individuals
Strategies for engaging patients to become active participants in their care.
Clinicians working with HIV-infected AOD abuse patients need to know how to set personal limits without abandoning patients. All healthcare workers, especially those who are themselves recovering AOD users, should be aware of the possibility that they may develop strong emotional ties to patients, which can influence their clinical care decisions.
Provision of services and care related to TB should be emphasized in the education and training of nurses, who should be able to perform skin testing and read test results. In many facilities, the ratio of nurses to patients is low; resources are needed to improve it. Clinical staff need to be educated about the dangers of TB so that they understand the importance of preventive interventions.
The concept of continual quality improvement (CQI) involves the continual review of program components and service delivery to ensure that defined levels of service are met. Mechanisms must be in place to identify when service delivery falls short of targets so that adjustments can be made. It is particularly important to have a CQI system in place in settings such as AOD abuse treatment programs that have not previously been oriented toward providing care for HIV-infected patients.
The ability to offer TB screening and CD4+ monitoring, supervised TB and PCP prophylaxis therapies, antiretroviral therapy, and postreferral followup are necessary components of any program treating HIV-infected AOD abusers. Every program should have a mechanism to ensure that patients who are appropriate candidates for prophylactic therapies receive them; this mechanism should include thresholds that trigger evaluation of the system of care. For example, if fewer than 90 percent of patients who are appropriate candidates for PCP prophylaxis are receiving it, a system problem may exist that requires evaluation.
Additional personnel and resources are needed to properly implement CQI evaluation and adjustment of services. It is inappropriate to add CQI responsibilities to the job description of a staff member who is already fully committed to other duties. The resources required to implement CQI will vary in different models of AOD abuse treatment.
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