Being Alive; March 1992
Nancy MacNeil

The clinical picture of HIV in drug using populations is significantly different from HIV in other populations.For example, there are almost no cases of Kaposi's Sarcoma in male IDUs who are also HIV+, but there is a five-fold risk of bacterial infection morbidity in HIV+ drug users vs. HIV+ non-drug users. IDUs are dying of bacterial pneumonia as a result of HIV infection, and yet do not meet the criteria for the CDC's definition of AIDS.

An epidemiology data base was established to look at this population and its particular manifestations of HIV. Many of the diseases found to be most common are not included in the CDC's AIDS definition: bacterial infections, pulmonary tuberculosis, sexually transmitted diseases, malignancies other than KS and lymphomas, HTLV I and II, and hepatitis. Clinicians and technicians must look beyond this limiting definition at the whole spectrum of diseases which drug users with HIV infection get. When IDUs develop pneumonia, it is more often bacterial pneumonia or TB-related, not PCP. (Bacterial pneumonia cannot be treated with bactrim or pentamidine.)

Certain malignancies, not considered AIDS-defining but definitely life-threatening, are occurring, mostly in male IDUs. These include lung cancer and cancers of the GI tract. In HIV+ women, cervical diseases and superimposed HPV infection are important clinical phenomena that must not be underestimated, whether the woman is a drug user or not. The diseases that women are presenting are likewise not encompassed by the CDC definition of AIDS.

CO-INFECTION IN HIV

Co-infection in HIV+ people may confuse the outcome of some clinical trials. Although hepatitis, delta-hepatitis (which can accompany hepatitis-B) and hepatitis-C show serologic abnormalities in the presence of HIV, they do not become clinically more active or more severe in people with HIV infection. However, HIV+ drug users are more likely to carry the hepatitis infection longer and thus remain infectious for a longer period of time.

40% OF METHADONE POPULATION HIV POSITIVE

There is a 40% HIV seroprevalence in the entire methadone-taking population. In a study of HIV+ asymptomatics in this group, it was found that a large proportion presented initially with clinical diseases such as bacterial pneumonia, endocarditis/sepsis, herpes zoster, and pulmonary TB. Of these, only herpes zoster is typically viewed as an early physical manifestation of immune decline. The study also showed that using CD4 counts is probably not the best way to determine whether or not these diseases will occur in this population. Another surrogate marker of HIV progression, beta-2 microglobulin levels in the blood, is also not useful in HIV+ drug users, because beta-2 levels are high in all drug users.

CLINICAL TRIALS

Many study participants use primary care services for medical complications caused by a mixture of substance abuse and HIV infection itself. Therefore, the ability to provide an array of social services, along with comprehensive medical care, including pediatric care, is a crucial, inseparable component in successful recruitment and retention of patients in clinical trials. This is a population that has been disenfranchised and marginalized, and is without access to health care of any kind. HIV comes with overall neglected health in these individuals. The single most crucial element in clinical trials is the inclusion of primary care services on site one-stop health care. Providing social services, as well as transportation back and forth for study visits, and a warm and non-judgmental research team are also key. There has also been a suggestion that incentive payments to participants be incorporated into the study protocol.

If researchers want to enroll IDUs in trials, they must first accept their life style, which for most IDUs is not abstinence. Whether individuals are using drugs intravenously or not, they can still participate in clinical trials. To get vital information on AIDS therapy in this population, as well as to ensure some equity of access to care, exclusion criteria should be carefully constructed so as not to rule out people on the basis of "active use" or any other aspect of life style.

UNDERSTANDING ADDICTION

Tolerance and dependence are two specific characteristics of drug addiction. Addiction occurs when a substance is required to maintain basic functioning. The compulsive, habitual, repeated use of a substance is continued in spite of harmful consequences, which the person involved recognizes fully. In other words, addicts know they're doing something which is self-destructive. Researchers must realize that addiction is something that the addicted individual cannot simply stop. The drug users' awareness of doing something destructive, and their perception of their ability to stop, are clearly clouded by denial and avoidance. The notion of repetitive, continued self destructive behavior, even in the face of adverse consequences, is important to the understanding of the phenomenon of addiction. Drug addiction itself, and the pathophysiology of how drugs affect the central nervous system, drive people to do unsafe things, such as use contaminated needles. There is vast documentation of people able, in a sense, to stand outside their addiction and tell you that they have destroyed their families and their lives, and yet they can't stop. It is not a simple question of morality or failure or lack of character. Drug addiction and abuse should be viewed as clinical phenomena.

DRUG WITHDRAWAL

Drug withdrawal in itself creates symptomatic nervous disorders, and a person's functioning is normalized when the drug is re-introduced. So it is not surprising that most addicts return to using drugs, even after significant periods of abstinence. However, there are individuals who are able to overcome addiction and take charge of their lives, and certainly those people deserve respect. To overcome addiction and to share experiences with others is an enormous and heroic endeavor. The notion of "Just Say `NO'" is naive and over-simplified. Twelve step programs, detox, residential programs, and sometimes methadone, are effective for addicts who want to get better. But first, the pain of continuing to do what they're doing has to be greater than the pain of giving it up.

URINE TOXICOLOGY

Observation of the arms for tracks, awareness of attitude problems, financial difficulties and perhaps frequent unexplained accidents are indications of substance abuse. Urine toxicology testing, though not standard practice, is used to determine if someone is a substance abuser, and perhaps it should be as routine as CT scans and other emergency room tests.Increasingly, researchers are faced with the compounding factor of cocaine or crack use. They are finding these drugs in their study participants through urine toxicology tests in both "on methadone" and "not on methadone" patients, and are interested in the interaction of AZT with methadone, of crack with AZT, and crack and methadone with AZT. Obviously, doctors can't prescribe or administer crack, and they don't routinely screen for cocaine because laws require that doctors report findings of illicit drug use to the Health Department. Screening urine to confirm drug use would be helpful in trial studies, and most researchers and clinicians admit that they have no intention of reporting cocaine or crack in the urine of study participants.

OVERLAPPING SYMPTOMS

Many of the medical problems that care providers see in drug users are due to the substances themselves, and some are due to HIV infection. There definitely is an overlapping of symptoms; the clinical manifestations of HIV infection can be combined with, masked by, or mimicked by the effects of drugs and alcohol. Certainly fever, infection and diarrhea are quite common in drug users. The bacterial infections they get are more severe when HIV is present. Constitutional symptoms of HIV such as weight loss, diarrhea, and fever may be caused either by drug use or withdrawal. Often so-called behavioral problems are misdiagnosed disorders associated with brain lesions or central and peripheral nervous system toxicities. (Often addicts will be labeled A.S.P. anti-social personality). It is absolutely imperative that clinicians look beyond stereotypes and prejudices that some people have, when treating drug addicts and recognize co-existent, parallel pathophysiology that may be occurring.

DRUG INTERACTION

In a study, scientists suggest starting drug users on 60mg to 65mg of methadone and steadily increasing the dose every one or two weeks, to a stabilized opiate dosage (which usually takes six weeks with an average dose of 90mg of methadone, and a maximum dose of 120mg). Medications and methadone exhibit interesting drug interaction. When prescribing rifampin (used to treat TB), one must double the dose of methadone within two or three days because there is an increase in the metabolism of methadone (due to the induction of certain enzymes) which can cause serious, immediate opiate withdrawal. Rifampin not only increases the metabolism of methadone, it also decreases the half life, so it is important to not only double the dose of methadone, but also to divide it. One should give two-thirds dose in the morning and one-third at night, because a person may experience the symptoms of withdrawal before the end of the usual 24 hour period. Another very important thing to be aware of when using rifampin is that drug users are very aware of the effects that drugs and medications have on their bodies, and when they realize that rifampin is causing withdrawal, they stop taking it. Prescribing rifampin alone is a set-up for drug resistant TB. Furthermore, the use of dilantin or phenobarbital with AZT can cause opiate withdrawal but at a slower rate. With dilantin, then, methadone dosages should be increased but not necessarily doubled.

Studies of AZT/methadone interaction have had mixed, if not conflicting, results. A higher level of AZT has been detected in patients on methadone receiving the same dose of AZT as patients not on methadone. AZT does not absorb methadone or cause opiate withdrawal, though the side effects of AZT mimic opiate withdrawal symptoms. Increasing methadone dosages does not make the side effects of AZT less severe. Also there does not appear to be any increased toxicity with comparable doses of AZT in drug users taking methadone or another opiate compared to those who are not. Although people on methadone tend to retain more AZT in their systems, researchers do not attribute this phenomenon to pharmacokinetic interactions of the two drugs. Some researchers think that there is absolutely no interaction between AZT and methadone, that the two medications work independently, without interfering with one another.

PAIN MEDICATIONS

When prescribing pain medications, one must keep in mind that a narcotics addict having pain needs more narcotic, not less. Dosages that may be considered dangerous for other people, may be required for IDUs, because of their astounding capacity and tolerance for narcotics. Methadone has absolutely no analgesic effect. It does not kill pain. For example, one should continue the same methadone dose but give higher, more frequent dosages of Demerol. There is a valid fear among HIV+ drug users that when they are in pain, they will not be medicated. Many in the medical community are of the opinion that if a patient is already on an opiate, they do not need pain medication; but nothing is further from the truth. When a person is on methadone maintenance, more methadone will not kill their pain. It is best to administer pain medication around the clock when a person is in the hospital. (When taking a patient off of medication, taper off gradually, not abruptly.) Often a struggle ensues between patient and care provider if the patient has to ask for pain-relieving medications.

A street practice of buying and selling antibiotics, that existed even before the AIDS pandemic, is relevant to clinical trials. In our culture there is a lot of self-medication, with illicit drugs as well as prescription drugs such as antibiotics. A drug addict can get any drug on the street, including penicillin, ampicillin, etc. (In some locations AZT is referred to as "Horse Pills" on the streets because of the Burroughs Wellcome unicorn logo.) So when clinicians ask if patients are taking "any other drugs," they should ask specifically about antibiotics and the use of AIDS-related therapies as well as marijuana or LSD and other so-called recreational drugs.

In summary: If you give dope fiends their juice, they will participate in clinical trials and if you pay them $20 they will return for their appointments. If researchers get over being judgmental, they might learn something from drug users. And totally disregard the CDC's definition of AIDS when treating OI's in this population.
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