Adherence and HAART HIV and Children

Adherence: Sine qua non…The potent capacity of HIV to modify it’s genetic background is the main reason for the virus’s ease to develop resistant pathogens. The force of HAART can only be maintained if antiretrovirals are taken at adequate doses without interruption. Strong adherence to the antiviral regimen is clearly a condition, “sine qua non…”. It is now clear, that lack of adherence is the most frequent reason for treatment failures. Thus, even more important than a plan how to salvage a failing treatment is a plan how poor adherence will be avoided.When nobody may know about HIV infectionHansjakob Furrer presented an illustrative case of an asylum seeking man who was treated for tuberculosis and advanced HIV infection. When this patient failed early during his antiviral treatment course, the numerous difficulties of this patient to understand and adhere to HAART became evident. As frequently observed in patients from Sub-Saharan Africa (also supported by the comment from Joe Eron) the different cultural background often makes antiviral treatment difficult. A basic understanding of the viral disease and the principle of action of the antiviral treatment is needed to motivate a patient to maintain not just a few weeks but also several years of uninterrupted antiviral treatment. Perhaps the major difficulty for this patient was associated with the stigma of HIV, the fact, that nobody in the asylum camp should hear about his HIV-infection.The second case just underscored the importance of a good motivation of the patient. In this case, the team actually got the partner of the patient involved to observe daily dosing of treatment, a special form of daily observed therapy (DOT). Nevertheless, the patient had a poor response to treatment and the non measurable protease-inhibitors in his plasma was a proof of poor adherence. Only after the patient got confronted with the failing treatment, the multiple personal difficulties of this patient (alcoholism with denial, inexistent communication within partnership) became obvious.The case clearly demonstrates the importance of a shared decision making between caregivers and patients. Patients need to understand why to take the drugs and they need to be well prepared and ready for the start of treatment.Can adherence be measuredThere is no gold standard for the measurement of adherence. Pill count is only used within clinical trials and is highly inaccurate. TDM is only informative is no drug level can be measured in plasma (as in our two cases). The MEMS system (see below) is currently the best tool to measure adherence. However, the power of the MEMS system is not in it’s capability to provethe patient that he is failing. The best use of MEMS can be made if it is used as a tool for the patient to help understand his difficulties in regular intake of pills.How much adherence is needed?Several studies have clearly shown that the adherence level required to maintain longterm viral suppression is greater than 95% (see figure). Not only is there a strong correlation between the level of adherence and the virological success rate. More important is the fact, that intermediate resistance is the most critical situation where resistant viruses are selected. Mathematical considerations suggest that antiviral treatment is more forgiving once complete viral suppression is established. Converseley, a strong level of adherence is especially critical during the first few weeks of treatment when the viral replication rate is still high.Can adherence be learned?Paradoxically, the first few days and weeks of treatment are often the times when a patient needs to learn how he can best take his pills without forgetting any. This paradoxical situation has lead the St. Gallen team to establish the so called MEMS-training period. Patients receive a MEMS cap, an electronical medication cap with an internal microchip and clock which records each opening of the caps. With the use of this tool, the team tries to help the patient understand the difficulties of the regular pill dosing and find ways to improve the critical situations that may be different for each patient.Ways to improve adherenceSeveral methods can be used to improve adherence. Principally the following issues need to be addressed:1. Motivation of the patient – shared decision making process2. Ease of administration (bid, qd, food restrictions etc.)3. Methods to control adherence (MEMS)4. Reminder-systems (family members, alarm clocks, cellular phones [SMS], associations with regular events in daily life such as tooth brushing…)The ease of drug administration is certainly an important point. The number of pills of a regimen have clearly been shown to be associated with treatment result (see figure). With the availability of drugs that can be taken once daily, further advances of the adherence may be expected. Today, a HAART regimen is only acceptable if it is a bid or qd regimen, without food restriction and a reasonable number of pills.The methods to further develop adherence must include technical and strategical ones. The MEMS system mentioned above can be used to help the patient understand his adherence and patterns of adherence failures. Based on a detailed analysis of the situation where a patient forgets to take his pills, additional tools can be installed that specifically address the problematic time points. Alarm clocks and the use of cellular phones are just a few of the numerous ideas that caregivers and patients develop themselves.Adherence is generally better if a close family member of the partner is taking part in the decision making and supports the patient in the adherence process.Todays discussion has shown that we all need to invest more in the future improvement of adherence and, more importantly, in our efforts to establish a shared decision making process with our patients that will help them to feel ready for treatment.PD Dr. med. Pietro Vernazza