The Clinical Guide to Supportive and Palliative Care for HIV/AIDS

A Clinical Guide to Supportive and Palliative Care for HIV/AIDS • Chapter 23: Medical Care in Advanced AIDSPhase I and Phase II trials are not trials for the patients’ benefit. Rather, their goals are to definetoxicity patterns, establish maximum tolerated dose, and complete trials in selected tumor types thatcould, if responses are seen, lead to advanced Phase II and Phase III trials. Responses measured inPhase I and26earlypicasPhase II trials rarely convert into prolonged survival for patients enrolled in thosetrials. 14Furthermore, systemic barriers obstruct palliative care program participation by these patients.Impediments dissuade programs from informing prospective patients, thereby restricting access.The added regulatory barrier that de facto prevents patients receiving disease-directed therapy fromeven being referred for hospice care 15 exacerbates dissonance between disease-directed and palliativeapproaches. Non-viable financial requirements argue against simultaneous care and are detrimentalto clinical research, to informed consent, and to best patient care. For example, hospiceprograms are required to absorb costs associated with disease-directed therapy (like HAART) andthe cost of treating patients’ side effects from investigational therapy.Consequently, when investigational therapy is completed, patients are often close to death. Bothpatient and loved ones have little opportunity to address end-of-life tasks. The physician and thepatient and family have focused often on the disease-directed therapies to the exclusion of end-oflifeissues and palliative care. 16The perceived dissonance between the goals of disease-directed therapy and palliative care leads topatient and physician reluctance to discuss concurrent application of both investigational therapyand palliative care. For the patient with advanced AIDS, participation in clinical trials should notbe a barrier to effective symptom management or intensive emotional support. A desire for optimalquality of life should not preclude clinical trials participation.AdherenceAnother sentinel event that appropriately triggers a patient/provider reassessment of the goals oftreatment is non-adherence to therapy. Current HAART regimens are complex. Patients are routinelyexpected to ingest between 6 and 20 pills a day, often on bid or tid dosing schedules withsignificant dietary restrictions.Patients experiencing virologic and clinical failure despite protease inhibitor therapy seem to fallinto two categories: those treated over an extended period of time with a variety of antiretroviralagents, and those whose adherence to a HAART regimen is inadequate to sustain viral suppression. 5Adherence research in other diseases with significantly less demanding regimens has documentedlevels of fully adherent behavior as low as seven percent. 17, 18 Furthermore, “….rates of compliancewith different long-term medication regimens for different illnesses in different settings tend toconverge to approximately 50%.” 19However, it should be noted that adherence rates vary greatly depending on measurement methodology.Moreover, adherence distribution curves are often U-shaped (not bell-shaped), suggesting thatclose to one third of patients are highly adherent, roughly one third are functionally non-adherentand the remainder fall in the 20%-to-80%-adherent range. This renders meaningless the “approximately50%” figure cited above.Adherence rates with chronic conditions also decline over time when reinforcement is absent. An80% rate of adherence, often adequate though not ideal in managing other diseases, is inadequatefor effective HAART. 20, 21 Several investigators have demonstrated a precipitous decline in HIV suppressionwith each 5% to 10% decrement in5, 22-25adherence.XXIIIU.S. Department of Health and Human Services • Health Resources and Services Administration • HIV/AIDS Bureau 483