As HIV spreads among injection drug users, treatment lags behind

Two studies show IDU therapy falling short

Two new studies indicate that although HIV rates continue to climb among injection drug users (IDUs) - who now account for more than one-third of reported cases - the majority are not receiving optimal drug therapy.1 In fact, a Baltimore study found that only one in seven patients received the most currently recommended therapy, even among patients who were seen at longstanding HIV specialty clinics.2

In a second study from Canada, where therapy is free under universal health care, only 40% (71) of 177 patients received any antiretroviral therapy (ART), and 66% (47) of those patients received double combinations of drug therapy.3

In Baltimore, where patients received care at Johns Hopkins and the University of Maryland, considered to be cutting-edge AIDS care providers, only half of HIV-infected IDUs obtained any kind of ART. Most surprising, though, was the finding that only 14% of patients received triple-combination therapy with a protease inhibitor.

The Baltimore study was a cross-sectional survey of self-reported ART use of 404 HIV-infected IDUs, conducted during 1996 and 1997. David D. Celentano, ScD, MHS, professor of epidemiology at Johns Hopkins School of Public Health in Baltimore, and colleagues found that 49% (199) had received no recent ART at all. Fourteen percent of patients (58) had received monotherapy, 23% (90) had received combination therapy without a protease inhibitor, and 14% (57) had received triple-combination therapy with a protease inhibitor. Recommenda tions from the International AIDS Society and the Department of Health and Human Services advocate at least triple-therapy regimens.4,5

"At this point, no one should be prescribed monotherapy with AZT," he says. "In the recommendations, it says do not prescribe [monotherapy]. Yet that's the most common treatment in the Baltimore sample."

Celentano says even more surprising was that most patients said they had obtained therapy at the "major centers of excellence" in the Baltimore area, such as AIDS clinics at Johns Hopkins and the University of Maryland.

"I think part of it is that physicians are very concerned about low adherence, the chaotic lifestyle of the patients, and [physicians] don't want to begin them on combination therapy until they're convinced that they're going to be able to take it as advised," he says. "There's a lot of worry about drug resistance, because if you develop resistance to one protease inhibitor, you've got resistance to the entire class of drugs."

The IDUs who were least likely to receive ART tended to be active drug users without clinical disease who had less contact with health care workers, says Celentano. That finding seems to indicate that physicians may not have provided therapy out of concern about compliance. But former drug users, even those who hadn't injected drugs in years, were not any more likely to receive ART than active drug users.

"In the eyes of the medical establishment, I think there is the belief 'Once a drug user, always a drug user,'" Celentano says. "I think that's a real problem. In somebody who stopped using five, six, seven years ago, there is no reason why they shouldn't be given the same chance everyone else gets."

Kenneth Mayer, MD, director of the Brown University AIDS Program in Providence, RI, says he also believes physicians discriminate against HIV-infected IDUs.

"We cannot [routinely] deny people life-saving medication because of some kind of ill-founded demographic bias where you think you can predict who is going to be adherent to [therapy] and who is not," he says. "Some [physicians] have this kind of simplistic view that if the person is asymptomatic and they're not going to be adherent, then you're wasting good drugs. You wait until the person is sicker and then they'll be more motivated. I think that's really a foolish idea, given that we tend to get our best results if we start [therapy] sooner."

If IDUs are noncompliant - they don't show up for appointments and they admit to not taking their ART, for example - not giving them medication may be justified, Mayer says. "I don't think clinicians should feel that they should give people medication no matter what when we are talking about the stakes being as high as this," he says. "But I think it's a cop-out for providers not to think of every single person who is HIV-infected who meets criteria as a potential candidate for antiretroviral therapy."

Mayer says there are "creative ways" to help IDUs remain adherent to ART. "You can get other health care providers and family members involved to try to motivate them, especially now that we have simpler regimens," he notes.

Renslow Sherer, MD, director of the Cook County HIV Primary Care Center in Chicago, treats many HIV-infected IDUs. There are about 2,000 HIV-infected patients at the facility, and 40% have a history of chemical dependency, he says. In an editorial accompanying the Baltimore and Canadian studies on IDUs, he makes the point that compliance with drug therapy is a problem for almost all HIV-infected patients. But the literature on hypertension indicates that patients are far more likely to take their medication if regimens are simplified.

"Many [HIV-infected patients] do require three-times-daily therapy, but a growing number can be given twice-a-day therapy, and increasingly, once a day," he says. "So there is actually quite a menu of options now. I haven't been using much three-times-daily medicine for that very fact."

For example, ritonavir/saquinavir (Norvir/ Invirase), nelfinavir (Viracept), and nevirapine (Viramune) can be used twice a day. Newer drugs such as adefavir can be used once a day, Sherer adds.

Look beyond stereotypes of IDUs

Sherer also says it is a mistake to categorize IDUs. "Oftentimes when physicians think of an injection drug user, they think of the stereotype of a criminally active, severely addicted person who is willing to do anything for the next fix," he says. "There clearly are such individuals. But there also are irregular or part-time users, users who are professionals such as stockbrokers and health care workers, among others. There are users who are holding down jobs and still using. It's a much more diverse group than is appreciated. So it's hard to generalize what their behavior is going to be."

Strangely, the high cost of ART doesn't appear to play a role in physicians' reluctance to prescribe ART to IDUs. The Canadian study found that physicians there were reluctant to prescribe ART to IDUs even though health care is free for Canadian citizens.

"There is universal health care, and all of the antiretroviral therapies are covered under this program, so that every HIV-positive person who is eligible according to the universal guidelines can receive triple therapy that works effectively," says the Canadian study's lead investigator, Steffanie A. Strathdee, PhD, associate professor of epidemiology at Johns Hopkins University. (Strathdee was formerly director of the epidemiology program at St. Paul's Hospital at the University of British Columbia in Vancouver, where the study was conducted.) "Yet these drug users who have been eligible on average for a year were still not receiving therapies."

Strathdee and colleagues looked at 177 HIV- infected IDUs who were eligible for ART. Patients were recruited through a prospective cohort study in 1996. Besides finding that 40% of eligible patients didn't receive ART, after adjusting for CD4 cell counts and HIV-1 RNA levels at eligibility, the odds of not receiving antiretrovirals were increased more than twofold for females and threefold for those not currently enrolled in drug or alcohol treatment programs. Younger drug users also were less likely to receive ART. Further findings were that physicians who had the least experience treating patients with HIV were more than five times less likely to prescribe ART to eligible patients.

"They were more likely to receive [ART] at all if the physician was experienced," says Strathdee. "But across the board, once patients were actually receiving therapy, 80% were receiving the therapy that was in accordance with the guidelines at the time they were prescribed. The problem isn't that they weren't getting the right therapy, the problem was that they weren't getting the therapy at all."

Strathdee says she is particularly troubled by those findings because there has been an outbreak of HIV in Vancouver in recent years.

"And when people are newly infected with HIV, they have a lot more virus in their bloodstream, and they're potentially a lot more infectious," Strathdee notes. "So if they had been receiving this combination therapy that was free, that would have dramatically lowered the amount of virus in their system, and potentially had an impact on this outbreak. So [ART] is not just about prolonging survival, it's also about preventing further transmission."

Why were women less likely to receive ART? Strathdee says one theory suggests a gender bias with females. "We know that exists with heart medications and other types of therapies in the general population," she says. "But it could be also more likely that females refuse therapy more often than men. That's something we need to explore further. If women aren't receiving antiretroviral therapy, there's also a risk to their fetus if they become pregnant."

But in general, compliance is a problem among IDUs. Many are homeless and may live chaotic lives that make it difficult to take five or six pills two or three times a day. "It's hard even for somebody with a stable lifestyle to be able to adhere to these regimens," Strathdee says.

Strathdee says the Vancouver study found that patients in drug or substance abuse treatment were more likely to receive ART, probably because they were exposed to the health care system.

"It gives us some indication that [substance abuse treatment] is a window of opportunity, and that we should be combining drug and alcohol treatment with antiretroviral therapy, because the two seem to go hand-in-hand," she explains.

Celentano says another opportunity for IDUs to receive ART is jail or prison. In the Baltimore study, being incarcerated meant IDUs were less likely to receive drug therapy.

"Incarceration is quite common in this population," he says. "Jails and prisons are really the opportune time to commence the medical care of these HIV-infected people. [Inmates are] generally not using [illicit] drugs in prison, and it's a situation where a nurse or physician assistant can provide directly observed therapy."

Perhaps the most important aspect of drug therapy in IDUs is the physician/patient relationship, Sherer says. He recommends spending two or more visits with patients before starting ART, providing informed consent, encouraging them to enter substance abuse treatment, and helping them stabilize chaotic factors in their lives such as homelessness, abuse, and mental illness.

"We're asking a lot," he says. "We're asking people to take five or 10 pills two or three times a day. Many of the patients feel perfectly fine, and we're asking them to take these pills life-long. Many of the drugs can make them quite sick, either temporarily or long-term. That's a tremendous challenge."

References

1. Centers for Disease Control and Prevention. Update: Syringe exchange programs - United States, 1997. MMWR 1998; 47:652-655.

2. Celentano DD, Vlahov D, Cohn S, et al. Self-reported antiretroviral therapy in injection drug users. JAMA 1998; 280:544-546.

3. Strathdee SA, Palepu A, Cornelisse PGA, et al. Barriers to use of free antiretroviral therapy in injection drug users. JAMA 1998; 280:547-549.

4. Carpenter CCJ, Fischl MA, Hammer SM, et al. Antiretroviral therapy for HIV infection in 1997: Updated recommendations of the International AIDS Society - USA panel. JAMA 1997; 277:1,962-1,967. [Updated July 1, 1998]

5. Department of Health and Human Services. Guidelines for the use of antiretroviral agents in HIV-infected adults and adolescents. MMWR 1998; 47(RR-5):43-82.