Laura W. Cheever, M.D.
The Hopkins HIV Report - November 1998

An important question for both patients and clinicians is, "How adherent do patients have to be?" In one study from the Pittsburgh VA and University of Nebraska, patients receiving protease inhibitors had their adherence carefully assessed over a six month period using a MEMS device, a pill bottle cap that electronically monitors the opening of medicine bottles [Paterson et al., I-172]. Results are illustrated in the figure and demonstrate the clear association between adherence and viral suppression, though even highly adherent patients may develop virologic failure.

Factors associated with non-adherence varied and were not consistent across all studies. Depression and African-American race were most consistently associated with non-adherence [Shelton et al., I-170, I-172, Cheever et al., I-178, Berge et al., I-212, Schult et al., I-215]. Illicit drug use was defined in various ways but was associated with poor adherence when defined as active use of heroin, crack cocaine, or stimulants [Walsh et al., I-171, Tuldra etal., I-177, I-178]. Surprisingly, the specific antiretroviral drug regimen was reported to have little impact on medication adherence. No significant difference was observed between bid and tid regimens, and there were no differences based on choice of protease inhibitors [I-171, I-172, I-177]. However, these studies were purely descriptive, and the data may reflect considerable selection bias. Motivated patients may be more likely to receive tid regimens than patients deemed less likely to be adherent, for example. In contrast, investigators at the University of Alabama reported that adherence may be greater with some drugs than others within a single regimen. For example, patients are more likely to miss multiple doses of ddI than AZT [Stewart et al., I-176].

The assessment of medication adherence was the subject of many abstracts. Studies presented consistently found that patient self-report over-estimated adherence as compared to electronic monitoring [McNabb et al., I-142, I-172, Melbourne et al., I-175]. Nevertheless, patient self-report is predictive of virologic response [I-170, I-212]. Patients were more honest when their adherence was assessed through an interactive computer program than when interviewed by their pharmacist; 36% of patients who reported complete adherence to their pharmacist admitted to missed doses on the computer interview [I-176]. Self-report, however, appeared more reliable than physicians' impressions of patient adherence. As with similar studies in non-HIV infected populations, physicians do a poor job at predicting non-adherence among their patients. In the Pittsburgh VA/ University of Nebraska study, 21% of the patients who were judged by their physicians as being <80% adherent had >95% adherence as measured by MEMS caps; and an additional one third were 80-95% adherent [I-172].

The only intervention trial to improve adherence was presented by our group at Johns Hopkins [I-178]. Adherence with PCP prophylaxis was increased by 16%, from 67% in the control group to 78% in the intervention group with the addition of a 10 minute nursing visit at the end of each regular clinic visit. The nursing visit focused on the importance of adherence and used a problem solving approach to overcome obstacles to adherence.

Investigators from Tulane University examined in detail the reasons why patients were not on protease inhibitor therapy [Michaels et al., I-236], and these reasons differed somewhat based on gender. For men, factors associated with not receiving a protease inhibitor, in a multivariate model, included: African-American race, substance abuse, CD4 >200 cells, no history of an opportunistic infection, and no clinic visit in the last 6 months. For women, associated factors were: CD4 >200 cells, no clinic visit in the last 6 months, and a history of incarceration.

The take home message from the conference is that adherence is low in many patient populations, and factors associated with adherence vary. The association between non-adherence and depression is clear, and clinicians should aggressively treat depression in patients considering antiretroviral therapy. Clinicians are poor judges of their patients' adherence, and inquiring about adherence in a non-judgmental fashion is important. Adherence can be improved with specific nursing interventions, but more controlled interventional trials are needed to assess which interventions will have the greatest impact on adherence with antiretroviral therapy.

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©1998. The Johns Hopkins University AIDS Service, Division of Infectious Diseases. Permission to use and reproduce portions of this newsletter is hereby granted provided that author and publication are fully credited and both copyright and permission notice appear with reprinted material. Inquiries may be directed to Sharon McAvinue, Managing Editor. Website: Johns Hopkins AIDS Service.

The original of this article can be found at http://hopkins-aids.edu/publications/report/nov98_3.html