Adherence

“a breath monitoring device developed by scientists at the University of Florida and Xhale Inc…[can monitor] medication adherence in high-risk individuals. ‘For HIV, it’s been shown that if you don’t take a very high percentage of your medication, you may as well not take medication at all,’ said Richard Melker, M.D., a professor of anesthesiology at the UF College of Medicine and chief technology officer for Xhale…Experts have tried literally hundreds, if not thousands, of ways to monitor drug adherence, ranging from daily log books to blister packs that record the time each pill is dispensed. Despite the money, time and effort devoted to these methods, Melker said only one works well: directly observed therapy, or DOT. ‘If you have a disease that is deemed to be a public health risk, authorities can put you into a program where you have to come to the clinic every day and be observed putting the pill into your mouth and swallowing it,’ Melker said…’[This] machine sits in your home and when it’s time for you to take your medication, it makes a beeping noise. If you don’t hit a button after about five minutes, it’s going to beep louder and louder until you come,’ Melker said. ‘If you don’t come after a certain amount of time, the machine can call the clinical trial coordinator and indicate that subject or patient didn’t take the medication as prescribed.’…’The doctor can see how often you took it and exactly what time. If it made the patient really sick or dizzy and they didn’t take it, they can find out why,’ Melker said. ‘It’s not just a question of did I or didn’t I take it, but when you took it or why you didn’t take it.’ The researchers developed the adherence monitor by incorporating minute amounts of an alcohol into a gel capsule. The additive, called 2-butanol, is one of many GRAS – Generally Recognized as Safe – compounds approved by the Food and Drug Administration for use in foods. ‘We wanted (patients) to swallow a chemical and have it transform into something else that’s easy to monitor,’ said Matthew Booth, Ph.D., an assistant professor of anesthesiology at the UF College of Medicine and an investigator in the study. [meaning that it will be easy to bypass the monitor by swallowing a small amount of this alcohol]”

“A LARGE number of Ugandan HIV/Aids patients on antiretroviral treatment have discontinued their treatment for at least one month because of the cost, side-effects or unavailability of the medicines, according to a new study by Makerere University researchers…The main reason given for therapy modification was its adverse effects, reported in 71.8 per cent of the patients who modified at least one drug in their regimen”

“A total of 230 patients were randomized; 199 started ART [anti-retroviral therapy], of whom 74% completed the 48-week study…At week 4, 82% of intervention patients had taken at least 90% of their prescribed ART doses, compared with 65% of controls; this group difference dropped to 12% at week 12 (72% versus 60%) and 11% at week 24 (66 versus 55%)…There were no group differences with respect to HIV-1 RNA throughout the study.”

“”I remember once, before I thought of the trade [selling half his antiretroviral medications to raise money for food], I would take the medicine without any food – just porridge alone. I nearly died. I got so weak, I developed ulcers which have not healed well until now.””

“Many [Canadian HIV youths] described being inconsistent with their treatment regimens, either not taking prescribed medication, taking medications only when they felt up to it, or needing breaks.”

“As the management of HIV improved we began to see longer survival especially for patients who were adherent with treatment…[but] substance abuse and mental health issues were each associated with poorer adherence to antiretroviral therapy [which mean that conclusions that better adherence leads to better outcomes might be false, and that it might be recreational drug abuse that leads to worse outcomes]…Bassetti et al in a Swiss cohort study found that patients not on therapy were more likely active injection drug users and had a lower educational level. Tucker et al found that cocaine, marijuana, amphetamines, sedatives and heavy alcohol usage were associated with poorer adherence”

“Anglo American estimated that 24% of its 140,000 workers in east and southern Africa were HIV-positive, said Brink. He said about 8,500 of the group's workers were at the stage of HIV where they needed AIDS drugs, but by the end of last year only 2,100 were on the company's treatment programme…]Brink said that 400 Anglo American workers had joined treatment programmes but quit. Their reasons varied, he said, but the majority had stopped treatment because of unpleasant side effects or difficulties in sticking to their pill-taking schedules.”

“The practice of forced drugging with [gastrostomy] tubes is also finding support across the country. A June 2000 University of California San Diego/ Northwestern University study of HIV-positive children found that implanting an abdominal tube can reduce a child's drugging time by five minutes. There's no indication that the children in the study were sick, or that the drugs improved their health. The doctors noted that one "older child" had to quit gymnastics because the tube made it too difficult. But she can take drugs faster. And that's what's important. Isn't it?”

“Measurement of adherence is imperfect and lacks established standards. Patient self-reporting is an unreliable predictor of adherence; however, a patient's estimate of suboptimal adherence is a strong predictor and should be strongly considered. A clinician's estimate of the likelihood of a patient's adherence is also an unreliable predictor. Aids for measuring adherence (e.g., pill counts, pharmacy records, "smart" pill bottles with computer chips that record each opening [i.e., medication event monitoring systems or MEMS caps]) might be useful, although each aid requires comparison with patient self-reporting. Clinician and patient estimates of the degree of adherence have been reported to exceed measures that are based on MEMS caps. Because of its complexity and cost, MEMS caps technology might be used as an adjunct to adherence research, but it is not useful in clinical settings.…Patient education should include the goals of therapy, including a review of expected outcomes that are based on baseline viral load and CD4+ T cell counts, the reason for adherence, and the plan for a mechanics of adherence. [improved health is not mentioned as a goal]”

“Aids patients on the government antiretroviral programme have started dropping out in small but worrying numbers that are said to be an indication of a bigger problem in the offing. [the article blames this on the fact that hospitals may charge 'modest' fees for distribution, but does not consider the possibility that toxicity is causing people to drop out]”

“During the programme’s first 15 months of operations, from February 1998 to the end of May 1999, HIV testing was offered to 9657 women, of which 6982 (72%) accepted the test. (Projet RETRO-CI conducted a randomised controlled clinical trial of the efficacy of short course zidovudine [AZT] at the clinic from April 1996 to February 1998) Of the 884 women who tested positive for HIV-1, 395 (45%) received their test results. Only 118 (35%) of the 333 women who tested as positive for HIV, who received their test results, and who were invited to return for follow up visits during this period eventually started taking zidovudine. Of the 215 women who did not start taking zidovudine, 181 (84%) had refused to return or discontinued follow up visits.”

“Over a 6-month period, 65 patients under antiretroviral regimens all including zidovudine [AZT] (300 mg twice a day) underwent TDM [Therapeutic Drug Monitoring]. Measurable concentrations of zidovudine (limit of quantification 10 ng/ml) were found in 52 patients (80%), whereas no zidovudine was found in 13 individuals [indicating that 20% of patients took no AZT. This is not proof that the remaining 80% were compliant]”

“Participation by the caregivers and child in the decision-making process is crucial, especially in situations for which definitive data concerning efficacy are not available. Issues related to adherence to therapy should be fully assessed, discussed and addressed with the child’s caregiver and the child (when age- appropriate) before the decision to initiate therapy is made.…Evidence indicates that adherence problems occur frequently in children. In a randomized treatment trial, caregivers reported that 30% of children missed one or more doses of antiretroviral medications in the preceding 3 days [65]; 42% of caregivers in an observational study reported at least one missed dose in the past week [68]. Using pharmacy refills to measure adherence, a study at a site with a comprehensive, multidisciplinary adherence program noted that only 42 of 72 children (58%) had refill rates of at least 75% over 6 months [66]. A study of another clinical program found that refill rates of 90% or greater adherence were met for only 12 of 35 children (34%) over one year [69]. These findings illustrate the difficulty of maintaining high levels of adherence and underscore the need to work in partnership with families to make adherence assessment, education, and support integral components of care.”

“…Currently available approaches to measuring adherence have notable limitations, and individual patient assessments by medical providers do not accurately predict adherence…The sensitivity of abnormally low drug levels to detect adherence of 90% or less was poor, ranging from 31 to 56%. Specificity at this threshold was higher, at least 90% for all drugs except indinavir. Sensitivity improved at lower adherence thresholds: at the 60% or less level, the sensitivity for all drugs pooled was 72%, rising to 83% among those of 50% or less. For efavirenz, a particularly long half-life drug, sensitivity at 90% or less was low at 44%; however, specificity was 100%.”

“After a median follow-up of 8.1 months, 61% of patients changed or discontinued their initial HAART regimen; 24% did so because of an adverse event. The events most commonly cited as the cause for discontinuation were nausea, vomiting, and diarrhea…Nausea/vomiting and not having AIDS at the time of HAART initiation [!] were associated with discontinuation due to an adverse event at any time”

“1 in 5 AIDS patients receiving free antiretroviral drugs from the Chinese government abandoned the combination of pills in the first 7 months of the program…Zhang Fujie, director of treatment for China's national AIDS control center…attributed the high dropout rate to the severe side effects caused by the drugs, and blamed the limited mix of low-cost drugs available in China and a shortage of qualified medical staff who can monitor patients and fine-tune treatment to manage side effects.”

“A random group of 283 patients infected with HIV was selected from those who attended a monographic HIV unit between November 2000 and January 2001 and had been prescribed HAART at least 6 months before. The percentage of adherence was measured by the ratio (the number of doses dispensed [divided by] the number of doses prescribed) x 100 and 95% was considered to be the adherence threshold…51.9% of study participants showed a good adherence”

“Mean self-reported adherence (percentage of doses taken as prescribed) for the day preceding each follow-up visit was 79%, and mean self-reported adherence for the week preceding each visit was 78%…Mean MEMS [special pill caps that count how often they are opened] adherence for the day preceding each followup visit was 57% and mean MEMS adherence for the week preceding each follow-up visit was 53%”

“A total of 41.7% (179) declared injecting drug use during the prior 6 months, while only 13.8% (59) were viewed by physicians as 'still actively injecting drugs'…women and older patients (30 years of age or more) were more likely to be perceived as adherent [to AIDS drugs]. Lower viral load and higher CD4 cell counts were also associated by physicians with good adherence [this belief produces a feedback system whereby good 'numbers' lead to a belief that patients are adherent encouraging them to tell patients that adherence to their drugs will result in good 'numbers', with nobody realizing that this is just circular reasoning]…those perceived to have stopped injecting drug use and not necessitating DMT [Drug Maintenance Treatment] (former IDUs) by physicians were also more likely to be considered 'adherent' than patients still viewed as active [illegal drug] users…non-active users in DMT remained to be perceived by physicians as less adherent than former users out of DMT…In the sub-set of 53 patients who [admitted] non-adherence to ART [Anti-Retroviral Therapy], the majority (32; 60.4%) had been classified as adherent by their physicians…among the 143 patients who reported adherence to ART…(30; 21%) [were] viewed as non-adherent by their physicians…although highly active antiretroviral regimens including PIs are usually considered as very hard to comply to, physicians in our study especially tended to underestimate problems of adherence, as they are reported by patients, for those receiving PIs.”

“Of the 213 patients [male and female victims of sexual assault] who were offered PEP [Post-Exposure Prophylaxis], 69 (32%) chose to initiate PEP, and 26 (12% of those initially offered PEP and 38% of those who initiated PEP) returned 1 week later to receive the additional 3 weeks of medications.”

“adherence to highly active antiretroviral therapy (HAART) may be problematic, particularly in HIV-infected children. Reasons for nonadherence include refusal, drug tolerability, and adverse reactions. We assess: 1) the potential benefits of gastrostomy tube (GT) for the improvement of adherence to HAART in HIV-infected children, and 2) the factors that may result in improved viral suppression after GT placement…The medical records of 17 pediatric HIV-infected patients, in whom GT was used to improve HAART adherence, were retrospectively reviewed for clinical and laboratory parameters. Each record was reviewed for the period of 1 year before and after GT insertion. The main outcome parameters were virologic (plasma HIV RNA polymerase chain reaction quantification) and immunologic (CD4 cell counts). [i.e. health was not a consideration]”

“The majority of participants had been placed on antiretroviral therapy by their physicians but, for a variety of reasons, had decided not to take the medication. They complained of side-effects such as diarrhea, loss of appetite, fatigue, neuropathy, and “just not feeling well.” Some developed resistance to their medications and were placed on other combinations of drugs. However, even changes in medication did not ensure adherence. Many protested the inconvenience associated with taking large numbers of pills and having to adjust meal times to coincide with pill schedules. One young man stated, “It’s hard to take that medicine, knowing I’ve got to go to that bottle three times a day keeps me stressed out. I don’t take no medication for anything.” Some indicated fear that medication would hasten death. One participant stated: “The people that were taking the medicine were dying faster than the ones not taking the medicine.”

Only a few spoke of the benefits of taking medications. Those individuals had become accustomed to the routine and had been diagnosed longer. They referred to rising T-cell counts and lower viral loads, weight gain, and a general sense of feeling healthier as evidence of the efficacy of medication. However, they were in the minority.”

“Because there is no gold standard to measure adherence, our assessment used four questions that were spaced throughout the HIV-specific portion of the interview [i.e. there is no way to accurately measure adherence as people are likely to exaggerate their adherence to please their healthcare workers, avoid conflict, retain benefits and so forth]…persons taking three drugs reported greater adherence [than those taking four]…there was no association [of adherence] with viral load, although only 13 person (31%) met all four adherence goals.”

“Both clinical experience and emerging data suggest that many patients with chronic HIV disease do not fully adhere to their highly-active antiretroviral therapy (HAART) regimens…Although available research consistently suggests that antiretroviral adherence is suboptimal, there are few consistent findings about the social, psychological, clinical, and behavioral factors associated with adherence. Studies conducted before highly-active multidrug therapies and viral load testing were available showed that many patients were nonadherent to zidovudine. Social support, attitudes about zidovudine, and belief in zidovudine efficacy were associated with greater adherence, whereas unstable housing arrangements and various measures of psychiatric disturbance were associated with worse adherence [but no word on whether adverse drug effects cause people to skip their doses]…More than one quarter of our study subjects (28%) reported taking on average fewer than 80% of prescribed antiretroviral medications per day over the prior week and were categorized as having poor adherence. Fewer (23%) reported taking on average between 80% and 99% of prescribed antiretroviral agents per day and were categorized as having fair adherence. Half (50%) reported [note that many people may over-estimate their adherence to keep their doctors happy] taking all prescribed antiretroviral agents and were categorized as having excellent adherence. Study subjects most commonly reported that they missed antiretroviral doses because they were busy or forgot, away from home, or experienced a break in their daily routine. Smaller proportions reported missing doses because they felt depressed or overwhelmed, were taking intentional drug holidays, or had run out of medication. [again no word on drug side effects]”

“18% (22) of the 123 patients were nonadherent [based on computerized prescription refill records]…The mean adherence rate among the ‘nonadherent’ patients was 72% and range from 0% to 87%; 77% had adherence rates of 70% to 90%, 14% of 50% to 70%, 5% of 20% to 50% and 5% of <20%…Adverse effects attributable to antiretroviral therapy were commonly documented. However, there was no difference in the rate of reported side effects in adherent patients as compared with nonadherent patients [which could mean that some people were refilling their prescriptions but not consuming all the pills]”

“we estimate that study participants may have experienced suboptimal therapeutic effects for more than 25% of their time on therapy”