The efficacy of the new combination antiretroviral therapies for treating HIV-positive individuals is unprecedented. Treatment has produced sustained suppression of viral replication and decreases in virus load to a level at which viral particles are undetectable in the blood of HIV-positive individuals. These therapies have resulted in a dramatically improved clinical outcome.

An important current issue is the ability of recovering drug abusers who are HIV-positive and living in poverty to adhere to these new complex and demanding regimens. Many clinicians believe that this group is too unreliable to take these medications, particularly in the early stage of their recovery from drug abuse when they are vulnerable to relapse (1).

The promise of highly effective antiretroviral therapy depends entirely on adherence to regimens that require at least 18 pills or capsules—some requiring refrigeration—taken on structured time lines, with food in some instances and on an empty stomach in others. If rigid adherence to medication schedules and food intake is not maintained, the virus may mutate and drug resistance or cross-resistance may develop (2), a devastating consequence for the individual. Less than excellent adherence can also have serious consequences for the community due to the transmission of drug-resistant HIV by nonadherent individuals and the increased virulence of the mutated strains. With the widespread introduction of these combination therapies into mainstream medical practice, nonadherence introduces an increasing risk of a second epidemic of more virulent, drug-resistant HIV strains.

Because of the recent development of combination antiretroviral therapies, the literature on adherence to HIV antiretroviral adherence focuses largely on AZT adherence. In non-drug-dependent populations, AZT adherence has ranged from 26 to 94 percent (3,4,5,6). Adherence rates are likely to be lower with the more complex combination therapies. One recent study found that adherence to HIV medications (including AZT), which was defined as the patient's refilling more than 80 percent of pharmacy prescriptions, was 63 percent in a multiethnic sample of veterans (7). Adherent patients tended to be other than black (p<.10), with lower scores on the Beck Depression Inventory (p<.04) and on the Profile of Mood States Total Mood Disturbance scale (p<.02). They used more adaptive coping skills (p<.03) and had more social support.

In another study, treatment nonadherence to antiretroviral medications (including AZT) among AIDS patients was associated with more distress and feelings of helplessness (8). Moreover, adherence was associated with better physical health status, based on Karnovsky scores collected at a 12-month follow-up.

A recent literature review suggested that the study of adherence to combination therapies among HIV-positive drug abusers has been largely neglected (9). In the few studies of this group, AZT adherence was reported to be greater among those whose medication ingestion was supervised and those with fewer psychiatric problems (10,11). Another research group found that better adherence to an AZT regimen was associated with greater social stability, greater perceived social support, increased perceived benefits of AZT use, and fewer perceptions of barriers to use (12). Our research group in Miami has reported that inconvenience and lack of access may play an important role in medication nonadherence among street-recruited HIV-positive drug abusers in Miami (13).

This column summarizes two preliminary studies that we conducted in 1997 to guide our effort to develop a brief intervention to enhance adherence to combination antiretroviral therapies among predominantly poor drug-abusing men.

Study 1

The first study, which was designed to better understand barriers to adherence to combination antiretroviral therapies among predominantly African-American, inner-city, drug-abusing men, involved multiple focus groups with 36 members of this population who had known their HIV-positive status for an average of five years. Thirty-two of the 36 participants (88 percent) were currently on the triple-drug-combination antiretroviral regimen. All men understood that these medication regimens could help HIV-AIDS patients improve dramatically, but only 46 percent knew what would happen if they did not strictly adhere to the regimen.

Almost all the men who had taken these medications admitted to a number of periods of nonadherence due to forgetfulness or side effects such as nausea and inability to retain the medicine, or by choice. In addition, most men admitted to multiple occasions when they had taken less than the prescribed amount of medication. Motivating factors for adherence to the regimen tended to be good social support and knowledge of how effective these agents can be. Adherence appeared to be related to the use of various strategies, including the use of pillboxes, pillboxes with a beeper, or calendar schedules or having significant others remind patients of their regimens.

Study 2

In our second pilot study, we focused on examining the effects of a brief intervention to enhance adherence to combination antiretroviral therapies among patients at the Miami VA Medical Center. Previous work with these patients has documented extremely poor adherence (14).

Specifically, among 290 HIV-positive veterans, only 17 percent of patients were fully compliant with the regimen, which was defined as having filled each prescription over a six-month period.

Consequently, we decided to examine the effects of a short behavioral intervention among 21 men at the center who had been nonadherent—that is, they did not refill their prescriptions of antiretroviral medications and other drugs to prevent opportunistic infections. The mean age of the group was 47, and more than half either lived alone (57 percent) or were homeless (25 percent). More than half also had a history of current or recent substance abuse. The mean number of medications prescribed was 8.3, consisting of antiretrovirals, prophylactic drugs for Pneumocystis carinii pneumonia and Mycobacterium avium complex, and medication to treat tuberculosis.

At an initial visit, each patient met individually with a doctoral-level pharmacist who provided a multicomponent weekly pill container and counseling. During this visit, patients were taught to fill the pill container and were asked to role play a day with their medication schedule. Patients' compliance, measured as monthly refills obtained for all medications, increased from 48 percent before counseling to 75 percent after counseling, while clinic visits increased from 66 percent to 76 percent. Furthermore, viral load reductions of .5 logs or greater occurred in 50 percent of patients. These findings suggest that individual counseling, coupled with consistent follow-up, can significantly increase adherence among HIV-positive individuals who do not adhere to medication regimens under usual-care approaches.

Collectively, the two preliminary studies described here and the studies found in the literature review suggest that adherence to combination antiretroviral therapies is problematic among poor, inner-city, African-American men. This finding is of major concern given that poor adherence to these regimens may increase the possibility of mutations in the HIV virus, leading to drug resistance or cross-resistance and more virulent strains. However, when drug-abusing patients are given easy and convenient access to medications and a brief behavioral intervention to increase knowledge of these regimens and enhance social networks, a greater percentage may demonstrate adequate adherence.

One promising direction in facilitating adherence to complex and demanding medication regimens that we recommend is the Medication Event Monitoring System (MEMS) Track Caps (Smart Caps, Aprex Corporation, Menlo Park, California). This technologically advanced medication bottle has a microchip fitted into the cap. The microchip provides a computerized record of when the bottle was opened and incorporates a beeping alarm to alert patients to take the medication at scheduled times. The cap closely resembles the cap of any pill container, except for an LED display on the top.

The manufacturer has also developed a multicompartment pill container, which became available in August 1997. Patients can remove individual compartments and carry them with them to cover the next dosage. Each compartment has an electronic device that records when and how many times the lid is opened, which should facilitate adherence to a complex medical regimen. The system allows more comprehensive tracking than was available at the time of the preliminary studies described here.

This work was partly funded by grants ROI DA08342 and ROI DA09520 to Dr. Malow from the National Institute on Drug Abuse.

The authors are affiliated with the University of Miami and the Miami Veterans Affairs Medical Center. Send correspondence to Dr. Malow at the University of Miami School of Medicine, Department of Psychiatry and Behavioral Sciences, D-22, 1425 N.W. Tenth Avenue, Miami, Florida 33136 (e-mail, mmalow@pol.net). Richard J. Frances, M.D., is editor of this column.