Diagnostic value of different adherence measures using electronic monitoring and virologic failure as reference standards.

Nonadherence to antiretroviral therapy is a substantial problem in HIV and jeopardizes the success of treatment. Accurate measurement of nonadherence is therefore imperative for good clinical management but no gold standard has been agreed on yet. In a single-center prospective study nonadherence was assessed by electronic monitoring: percentage of doses missed and drug holidays and by three self reports: (1) a visual analogue scale (VAS): percentage of overall doses taken; (2) the Swiss HIV Cohort Study Adherence Questionnaire (SHCS-AQ): percentage of overall doses missed and drug holidays and (3) the European HIV Treatment Questionnaire (EHTQ): percentage of doses missed and drug holidays for each antiretroviral drug separately. Virologic failure prospectively assessed during 1 year, and electronic monitoring were used as reference standards. Using virologic failure as reference standard, the best results were for (1) the SHCS-AQ after electronic monitoring (sensitivity, 87.5%; specificity, 78.6%); (2) electronic monitoring (sensitivity, 75%; specificity, 85.6%), and (3) the VAS combined with the SHCS-AQ before electronic monitoring (sensitivity, 87.5%; specificity, 58.6%). The sensitivity of the complex EHTQ was less than 50%. Asking simple questions about doses taken or missed is more sensitive than complex questioning about each drug separately. Combining the VAS with the SHCS-AQ seems a feasible nonadherence measure for daily clinical practice. Self-reports perform better after electronic monitoring: their diagnostic value could be lower when given independently.

Prevalence and correlates of nonadherence to antiretroviral therapy in a population of HIV patients using Medication Event Monitoring System.

Nonadherence to antiretroviral therapy (ART) jeopardizes good clinical outcome in people living with HIV. In a single-center prospective study, prevalence and correlates of nonadherence were investigated in 43 patients on ART. Nonadherence was assessed using Medication Event Monitoring System (MEMS), self-report and collateral report of treating physicians. Based on MEMS data, median taking adherence, dosing adherence, and timing adherence was 98% (interquartile range [IQR] = 5.3), 91.5% (IQR = 18), and 86% (IQR = 31.5), respectively. The median number of drug holidays per 100 days was 0.8 (IQR = 4.8). The prevalence of nonadherence measured by MEMS was 40%. Self-reported nonadherence and collateral report of nonadherence by physicians varied from 5% to 41% and 24% to 28%, respectively. Patients were categorized as adherent or nonadherent based on a clinically validated algorithm derived from MEMS parameters. Nonadherent patients used significantly more escaping coping strategies (p = 0.003) and planned problem solving strategies (p = 0.049), were prescribed significantly more antiretroviral medications (p = 0.02) and were significantly longer on ART (p = 0.04) than adherent patients. Identified correlates of nonadherence may help clinicians in detecting patients with HIV at risk for nonadherence and can support the development of adherence enhancing interventions.

A combination of poor adherence and a low baseline susceptibility score is highly predictive for HAART failure.

The relationship between adherence, virological response to highly active antiretroviral therapy (HAART) and the presence and development of genotypic resistance was assessed in 41 HIV-infected patients on HAART. Four adherence parameters (drug taking adherence, dosing adherence, timing adherence and drug holidays) were scored prospectively using electronic event monitoring. Genotypic resistance at baseline and after therapy failure was scored retrospectively and a genotype-based susceptibility score was calculated. Overall median adherence rates were high. All adherence parameters were better in virological responders (n=31) compared to non-responders (n=10), drug taking adherence and number of drug holidays being significantly different. Responders had a significantly higher susceptibility score. Stepwise logistic regression showed that the number of drug holidays and a low susceptibility score were highly predictive for therapy failure. Despite the presence of a limited number of baseline resistance mutations, perfectly adherent patients can control virus replication for a prolonged period.

Nonadherence to highly active antiretroviral therapy: clinically relevant patient categorization based on electronic event monitoring.

Adherence to highly active antiretroviral therapy (HAART) is crucial, but which aspects of drug-taking behavior are important remain largely unknown. In a prospective observational study, 43 HIV-1-infected patients taking HAART underwent electronic event monitoring (EEM). Taking adherence was defined as the percentage of doses taken compared with the number prescribed, dosing adherence was defined as the percentage of days on which all doses were taken, and timing adherence was defined as the percentage of doses taken within 1 hr of the time prescribed. Drug holidays were defined as periods of no drug intake for >24 hr. Cluster analysis, including the four EEM parameters, was used and refined to construct an algorithm to discriminate patients. Patients were categorized as nonadherent if they had a taking adherence of <90%, or a dosing adherence of <75% and at least 1 drug holiday, or a timing adherence of <80% and at least 1 drug holiday, or >6 drug holidays per 100 days. All four EEM parameters differed significantly (p < 0.0001) between the two groups. Adherent patients had a better outcome, as shown by a larger drop in viral load (p = 0.011) and rise in CD4+ cell count (p = 0.035), showing that the algorithm-based categorization is clinically relevant.