The economic viability of antiretroviral adherence interventions

In this issue of The Green Journal, Goldie et al (1) evaluate the cost-effectiveness of several interventions designed to improve adherence to medications for human immunodeficiency virus (HIV) infection. Adherence to an antiretroviral regimen is important, and good adherence is thought to be associated with a higher likelihood of realizing the full benefit of potentially lifesaving highly active combination antiretroviral therapy (2,3). In contrast, nonadherence is thought to be associated with increases in morbidity and mortality, greater complexity and cost of antiviral management, and possibly generation of drug-resistant HIV strains in both patients and those infected by them. Yet using antiretroviral medications correctly over long periods is difficult for a variety of psychological and practical reasons, even among patients who understand the potential consequences of nonadherence. These facts have made investments in adherence support programs seem sensible. Both HIV adherence support programs and research on the subject have become commonplace at centers in both highand lowincome countries. However, many fundamental questions about support in HIV disease remain. Two questions seem particularly important. First, does better adherence predict better long-term outcomes? Observational findings indicate that higher adherence is associated with better short-term viral suppression (3,4), but the association between adherence and protection against antiretroviral resistance is complex (5). It is unclear how long the effects of greater adherence on HIV suppression persist, or if programs to increase adherence would have the same effects. Second, if improving adherence is beneficial, how can patient adherence be improved in the long term? In high-income settings, electronic reminders are relatively easy to implement, but no published studies have demonstrated their effectiveness in HIV-infected patients. Investigators apparently doubt the adequacy of reminders alone; searches of the National Institutes of Health’s Computer Retrieval of Information on Scientific Projects (CRISP) and the VA’s Health Services Research and Development databases indicate that U.S.-funded studies in progress generally combine reminders with intensive behavioral or motivational strategies. Also, systematic reviews of adherence support interventions for various chronic diseases indicate that almost all interventions effective for long-term care are complex (6). Programs involving directly observed therapy are conceptually straightforward, but are operationally difficult and intensive. Other than those designed for institutionalized populations, directly observed therapy programs for HIV-infected patients are essentially all “modified,” in that only some doses are directly observed, and intensive (often outreach-oriented) case management is often incorporated. Studies demonstrating the effectiveness of such modified programs have not been published. Moreover, lifelong directly observed therapy is clearly problematic, and studies of transitioning from supervised therapy to independent medication self-management are lacking. It is in this context that Goldie et al assess what level of investment in HIV adherence interventions is reasonable in high-income settings. The authors extend Freedberg et al’s well-known Monte Carlo simulation model to estimate the likely impact of adherence interventions on patients’ costs of care and life expectancy in high-income settings (7). The assessed interventions were electronic reminders and dispensers/monitors, which are relatively inexpensive, and directly observed therapy, which can range from being expensive to very expensive. The model assumed varying degrees of efficacy from the interventions in three simulated cohorts, and then simulated the impact of the programs and the resulting improvement in viral suppression. Because the costs of both the intervention and care itself accrue with increasing life expectancy, costs per quality-adjusted life-year are positive. However, the authors found that, by the usual standards of costeffectiveness, the ratios of costs to gains were reasonable for a $100-per-month intervention in the early disease cohort and were very reasonable in the late disease cohort with only a modest improvement in viral suppression. In contrast, the ratios of costs to gains were never reasonable for a $1000-per-month intervention in either cohort, even if maximal improvements in viral suppression were achieved. This analysis is innovative and provocative because it demonstrates how medicine can adapt the sound busiAm J Med. 2003;115:672– 673. From the Department of Medicine (SAB, ALG), VA San Diego Healthcare System and University of California, San Diego, La Jolla; and RAND Health (SAB), Santa Monica, California. Requests for reprints should be addressed to Samuel A. Bozzette, MD, PhD, Health Services Research and Development, Mail code 111N1, VA San Diego Healthcare System, 3350 La Jolla Village Drive, La Jolla, California 92161, or sbozzette@ucsd.edu.