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PubMed2000

Adherence to protease inhibitor therapy and outcomes in patients with HIV infection.

BACKGROUND: Combination antiretroviral therapy with protease inhibitors has transformed HIV infection from a terminal condition into one that is manageable. However, the complexity of regimens makes adherence to therapy difficult. OBJECTIVE: To assess the effects of different levels of adherence to therapy on virologic, immunologic, and clinical outcome; to determine modifiable conditions associated with suboptimal adherence; and to determine how well clinicians predict patient adherence. DESIGN: Prospective, observational study. SETTING: HIV clinics in a Veterans Affairs medical center and a university medical center. PATIENTS: 99 HIV-infected patients who were prescribed a protease inhibitor and who neither used a medication organizer nor received their medications in an observed setting (such as a jail or nursing home). MEASUREMENTS: Adherence was measured by using a microelectronic monitoring system. The adherence rate was calculated as the number of doses taken divided by the number prescribed. Patients were followed for a median of 6 months (range, 3 to 15 months). RESULTS: During the study period, 45,397 doses of protease inhibitor were monitored in 81 evaluable patients. Adherence was significantly associated with successful virologic outcome (P < 0.001) and increase in CD4 lymphocyte count (P = 0.006). Virologic failure was documented in 22% of patients with adherence of 95% or greater, 61% of those with 80% to 94.9% adherence, and 80% of those with less than 80% adherence. Patients with adherence of 95% or greater had fewer days in the hospital (2.6 days per 1000 days of follow-up) than those with less than 95% adherence (12.9 days per 1000 days of follow-up; P = 0.001). No opportunistic infections or deaths occurred in patients with 95% or greater adherence. Active psychiatric illness was an independent risk factor for adherence less than 95% (P = 0.04). Physicians predicted adherence incorrectly for 41% of patients, and clinic nurses predicted it incorrectly for 30% of patients. CONCLUSIONS: Adherence to protease inhibitor therapy of 95% or greater optimized virologic outcome for patients with HIV infection. Diagnosis and treatment of psychiatric illness should be further investigated as a means to improve adherence to therapy.

Adult↗

PubMed1990

Characterization of monocyte adherence to human macrovascular and microvascular endothelial cells.

The interaction of monocytes with cultured large vessel venous and arterial endothelial cells (EC) and with cultured microvascular EC was studied. Analysis of time-lapse microcinematographic video recordings showed that monocytes adhere rapidly to the surface of EC and subsequently remain spherical and fixed to the initial site of adherence. Some monocytes adherent to EC stretch out within 30 to 90 min and migrate over the EC surface or become stretched for about 10 to 30 min and then detach from the EC surface and move rapidly over the EC monolayer. It was shown that the interaction of monocytes with EC is dynamic, that the morphology of monocytes adherent to EC changes constantly, and that stretching of the monocytes over the surface of the EC is not an inevitable and irreversible consequence of binding. A quantitative adherence assay was developed in which both the morphology and the number of monocytes bound to EC were determined. For each type of EC the number of monocytes bound to a single EC was found to be linearly related to the number of monocytes added and was lower for smaller EC. The adherence of monocytes to venous and arterial EC followed a different time course than the adherence to capillary EC and adherence to both types of macrovascular EC was higher than adherence to microvascular EC was higher than adherence to microvascular EC. The percentage of adherent monocytes with a stretched morphology was lower when these cells were adherent to capillary EC than to both types of macrovascular EC and increased upon addition of serum. Adherence of monocytes to venous, arterial, and capillary EC was partially inhibited by mAb directed against the alpha-chain of lymphocyte function-associated Ag-1 or C3bi receptor (with mAb LM2/1, but not with mAb OKM1) and by mAb against the common beta-chain of the three leukocyte adhesion molecules. The degree of inhibition of monocyte adherence to EC by mAb against lymphocyte function-associated Ag-1 alpha and the common beta-chain was dependent on the type of EC and was higher for venous EC (57 to 70% inhibition) than for arterial (40 to 44% inhibition) and capillary (44 to 49% inhibition) EC. Inhibition of monocyte adherence obtained with anti-C3bi receptor-alpha mAb was similar for each EC type. mAb against p150, 95 did not affect adherence. None of the mAb could block binding completely; combinations of the mAb also did not result in increased inhibition of monocyte adherence to EC.

Antibodies, Monoclonal↗

PubMed1986

Differentiation of cellular processes involved in the induction and maintenance of stimulated neutrophil adherence.

Neutrophil adherence stimulated by phorbol myristate acetate (PMA) was investigated by quantitating the attachment of 51Cr-labeled neutrophils to plastic surfaces and to the endothelium of umbilical veins mounted in compartmentalized Lucite chambers. PMA-induced adherence could be functionally separated into an induction phase requiring cellular metabolism and a Mg++ dependent maintenance phase that was independent of cellular metabolism. Thus, metabolic inhibitors (N-ethylmaleimide, 2-deoxyglucose) blocked adherence when added to neutrophils prior to PMA, but did not cause detachment of cells adhering as a consequence of prior exposure to PMA. PMA failed to induce adherence of neutrophils incubated at low (0.4 degree C) temperature, but temperature reduction, even for prolonged periods, did not cause detachment of adherent cells. Thus, the attractive forces that mediate stimulated adherence persist independently of any sustained metabolic response to the inducing stimulus. However, removal of Mg++ from the media above adherent cells resulted in immediate detachment, indicating that the cation was required for the persistent expression or maintenance of the attractive forces involved. The extent of stimulated adherence correlated well with the extent of degranulation when rates were varied by limiting the incubation time or stimulus concentration. This correlation was not absolute; in the absence of Mg++, PMA induced degranulation normally but failed to enhance adherence. To explain these findings, we investigated the possibility that PMA-stimulated adherence was maintained by Mg++-dependent cellular adherence molecules released during exocytosis. Supernatants of stimulated neutrophils were devoid of adherence-promoting activity, and only weak activity was recovered in supernatants of mechanically disrupted neutrophils. PMA effectively stimulated the tight adherence of degranulated neutrophil cytoplasts to plastic surfaces and did so in the absence of stimulated granule enzyme release. Thus, conditions have been identified under which degranulation occurs in the absence of adherence (removal of Mg++) and adherence occurs without concurrent degranulation. Since neutrophil cytoplasts do contain some granule products and granule material can be identified on cytoplast membranes, it is possible that degranulation or granule products may be involved in the adherent response. However, hyperadherence was shown to develop in the absence of de novo degranulation.(ABSTRACT TRUNCATED AT 400 WORDS)

Cell Adhesion↗

PubMed1985

The role of neutrophil membrane glycoprotein GP-150 in neutrophil adherence to endothelium in vitro.

We have previously described two patients with a congenital defect in neutrophil function characterized by an inability to form pus. The patients' neutrophils lack a membrane glycoprotein of mol wt 150,000 daltons (GP-150) on analysis by SDS-PAGE. This glycoprotein is part of a membrane antigen complex recognized by the murine monoclonal antibody (MoAb) 60.3. Addition of MoAb 60.3 to normal neutrophils produces defects in chemotaxis and phagocytosis in vitro similar to those observed in the patients. Since neutrophil adherence to vascular endothelium is prerequisite to neutrophil emigration in vivo, we examined the interaction of the patients' neutrophils and normal neutrophils treated with MoAb 60.3 with cultured endothelium. Adherence was determined as the percentage of 51Cr-labeled purified peripheral blood neutrophils which remained adherent to plastic wells or endothelial monolayers after a 45-minute incubation at 37 degrees C. The percentage of neutrophils from patient 1 remaining adherent to uncoated, fibronectin-coated, or laminin-coated plastic was similar to that observed in normal neutrophils (55% to 84% adherence with normal neutrophils v 73% to 78% adherence with the patient's neutrophils and 63% to 82% adherence with MoAb 60.3-treated normal neutrophils). The adherence of the neutrophils from patient 1 and MoAb 60.3-treated normal neutrophils to human or bovine endothelium in serum-free medium was also not significantly different from that observed in normal neutrophils (less than 10% adherence with normal, MoAb 60.3-treated, and patient neutrophils). In medium containing 10% autologous or heterologous human plasma, however, the adherence of neutrophils from patient 1 or MoAb 60.3-treated normal neutrophils to endothelial monolayers was significantly reduced (35% +/- 7% of normal neutrophils in seven experiments). Although phorbol myristate acetate (PMA) (10 ng/mL) and calcium ionophore A23187 (10(-5) mol/L) markedly increased the adherence of normal neutrophils to endothelial monolayers in serum-free medium (40% to 85% adherence), neither agent increased the adherence of the neutrophils from patient 1 or normal neutrophils treated with MoAb 60.3 (less than 5% adherence). The adherence of PMA-activated neutrophils from patient 2 to endothelial monolayers was also markedly decreased when compared with that of normal neutrophils. Postsecretory cell-free supernatants from PMA-activated normal neutrophils failed to augment adherence of neutrophils from patient 1 (less than 5% adherence).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1993

Effects of viral and mycoplasmal infections, ammonia exposure, vitamin A deficiency, host age, and organism strain on adherence of Mycoplasma pulmonis in cultured rat tracheas.

Adherence to host cells is thought to be a pathogenetic mechanism in mycoplasmal diseases, thus, factors affecting adherence could affect disease expression. To determine whether factors that affect expression of Mycoplasma pulmonis respiratory disease in rats alter adherence of the organism to respiratory epithelium, we studied adherence of radiolabelled M. pulmonis in perfused whole rat tracheas. Adherence was significantly increased in tracheas from rats with sialodacryoadenitis virus infection or vitamin A deficiency (103 +/- 16% and 112 +/- 29% of control means, respectively), but Sendai virus infection, ammonia exposure, and host age (40 versus 8 weeks) were not associated with increased adherence. We also assessed the relationship between adherence and virulence of M. pulmonis strains. The virulent strain 5782C was more adherent (51 +/- 7%) than the type strain, PG34(Ash), and a polystyrene-adherent, hemadsorbing UAB CT subclone was more adherent (229 +/- 40%) than a UAB CT subclone that does not adhere to polystyrene or erythrocytes. PG34(Ash) and the UAB CT subclones caused rhinitis only; however, the adherent UAB CT subclone caused significantly more severe rhinitis than either the nonadherent subclone or PG34(Ash) as determined by scoring of histologic sections. To determine whether M. pulmonis itself induces changes in respiratory epithelium resulting in enhanced adherence, we studied adherence in tracheas from rats inoculated with M. pulmonis 3 weeks earlier. Adherence was increased 64 +/- 22%, compared with that in tracheas from control rats. Adherence in infected tracheas treated with tetracycline for 2 days was not increased, indicating that M. pulmonis-induced changes in epithelial adherence are rapidly resolved after elimination of infection.

Age Factors↗

PubMed2002

A prospective study of predictors of adherence to combination antiretroviral medication.

OBJECTIVE: Adherence to complex antiretroviral therapy (ART) is critical for HIV treatment but difficult to achieve. The development of interventions to improve adherence requires detailed information regarding barriers to adherence. However, short follow-up and inadequate adherence measures have hampered such determinations. We sought to assess predictors of long-term (up to 1 year) adherence to newly initiated combination ART using an accurate, objective adherence measure. DESIGN: A prospective cohort study of 140 HIV-infected patients at a county hospital HIV clinic during the year following initiation of a new highly active ART regimen. MEASURES AND MAIN RESULTS: We measured adherence every 4 weeks, computing a composite score from electronic medication bottle caps, pill count and self-report. We evaluated patient demographic, biomedical, and psychosocial characteristics, features of the regimen, and relationship with one's HIV provider as predictors of adherence over 48 weeks. On average, subjects took 71% of prescribed doses with over 95% of patients achieving suboptimal (<95%) adherence. In multivariate analyses, African-American ethnicity, lower income and education, alcohol use, higher dose frequency, and fewer adherence aids (e.g., pillboxes, timers) were independently associated with worse adherence. After adjusting for demographic and clinical factors, those actively using drugs took 59% of doses versus 72% for nonusers, and those drinking alcohol took 66% of doses versus 74% for nondrinkers. Patients with more antiretroviral doses per day adhered less well. Participants using no adherence aids took 68% of doses versus 76% for those in the upper quartile of number of adherence aids used. CONCLUSIONS: Nearly all patients' adherence levels were suboptimal, demonstrating the critical need for programs to assist patients with medication taking. Interventions that assess and treat substance abuse and incorporate adherence aids may be particularly helpful and warrant further study.

Adult↗

PubMed2002

Adherence discourse among African-American women taking HAART.

Low adherence is the single most important challenge to controlling HIV through the use of high acting anti-retrovirals (HAART). Non-adherence poses an immediate threat to individuals who develop resistant forms of the virus as well as a public health threat if those individuals pass on treatment-resistant forms of the virus. To understand the concerns and perceptions that promote or deter adherence to antiretroviral medication by HIV-positive African-American women, we conducted in-depth interviews with 15 African-American women taking HAART. We focused on the discourse and narratives women use in talking about their adherence practice. Discourse analysis was utilized to identify and explore the sources of influence used by these women in describing their adherence practice. Roughly a third of the sample fell into each of the three self-assessed adherence categories: always adherent, mostly adherent and somewhat adherent. Among the 'always adherent', 80% of the sources of influence cited supported adherence, while only 48% and 47% of the authoritative sources cited by women in the 'mostly' and 'somewhat' categories supported adherence. Each self-assessed adherence group was characterized by its own distinctive discourse style. Findings suggest that adherence to HAART among African-American HIV-positive women would be improved by identifying those influences undermining adherence. Focused study of the 'always adherent' types is recommended.

Adult↗

PubMed2002

Prevalence, predictors, and outcomes of early adherence after starting or changing antiretroviral therapy.

The objectives of this research were to assess prevalence and predictors of early antiretroviral therapy adherence using multiple indicators and to estimate effects of early adherence on subsequent HIV viral load and CD4+ lymphocyte responses. Study subjects were adults with HIV infection referred to an antiretroviral therapy-monitoring clinic for initiation or change in therapy between March 1998 and June 1999. The design was a prospective observational cohort involving baseline interview followed by 30 days of electronic adherence monitoring (MEMS), 30-day interview, and follow-up viral load at 1, 3, and 6 months. Adherence indicators included MEMS therapeutic coverage, observed/expected cap openings, and self-reported adherence assessed at 30 days. Of 235 consenting patients, 60 (26%) failed to complete 30 days of electronic monitoring (noncompleters). At 6 months, mean change from baseline plasma viral load was inferior among noncompleters (0.5 log vs. 1.7 log). Predictors of adherence, varying by adherence metric, included: gender, race, prior antiretroviral therapy experience, substance abuse, prior adherence behavior, health beliefs, and pharmacist prediction of adherence. Self-reported adherence was more sensitive in predicting viral load responses than MEMS-based measures and identified poor adherence at earlier time points. Approximately a quarter of consenting patients were unable to complete 30 days of MEMS monitoring, and early drop out was a poor prognostic sign. Predictors of adherence varied depending upon how adherence was measured. Differences in virologic response between patients with optimal or poor adherence may not emerge until several months after regimen change or initiation. Structured assessment of self-reported adherence is an inexpensive and useful tool to assist clinicians in monitoring adherence.

Adult↗

PubMed2002

Predictors of medication-refill adherence in an indigent rural population.

OBJECTIVE: We evaluated the association of medication refill adherence with demographic and prescription characteristics to determine whether such factors could guide intervention strategies in an indigent rural population. METHODS: The study was conducted at a University-based internal medicine practice serving an indigent rural population. Refill data for diabetes, hypertension, and hypercholesterolemia drugs from a closed pharmacy system were used to calculate mean adherence (for all drugs taken by each patient) and minimum adherence (that of the least adhered to drug) for 1984 patients during a 9-month period. RESULTS: Mean refill adherence was <80% for 33% of the population and minimum refill adherence was <80% for 55% of the patients. Increasing age, race (white), and prescription length were associated with higher mean and minimum adherence, independent of income, prescription copay, and insurance status. Number of drugs taken had a positive mean but negative minimum adherence association. Gender, number of primary care visits, and dosage schedule were not independently associated with adherence. The model explained 6.8% of the variance in mean adherence. CONCLUSIONS: In a rural indigent population, medication refill adherence was associated with race, age, and prescription length, though these factors explained only a small amount of adherence variability. Although ingestion adherence is the goal, refill adherence is a necessary condition for ingestion adherence. To enhance adherence, physicians need better predictors to target their efforts to patients most in need of attention. Prescription claims data could serve this purpose.

Diabetes Mellitus↗

PubMedDate not supplied

Testing a nurse-tailored HIV medication adherence intervention.

BACKGROUND: The relationship between patient adherence and treatment outcomes has been documented across chronic health conditions, but the evidence base for effective adherence interventions in human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) requires more rigorous research and reporting. OBJECTIVES: The aims of this study were to determine whether a tailored, nurse-delivered adherence intervention program--Client Adherence Profiling and Intervention Tailoring (CAP-IT)--improved adherence to HIV medications, compared with standard care, and to identify the relationship among adherence measures. METHODS: A randomized controlled trial (RCT) with repeated measures was used to test the efficacy of CAP-IT over a 6-month period. A convenience sample of 240 participants was recruited from a freestanding public HIV/AIDS clinic in Houston, TX, that provides medical, psychological, and pharmaceutical services for over 5,000 clients. Study instruments and measures included demographics; chart audit to capture CD4 count, viral load, and prescribed medications; health literacy; and five measures of adherence (AIDS Clinical Trial Group-Revised Reasons for Missing Medications, Morisky Self-Report of Medication Non-Adherence, Pill Count, Medication Event Monitoring System [MEMS] caps, and Pharmacy Refill). RESULTS: A logistic regression using generalized estimating equations method showed no significant differences over time on the five medication-adherence measures between the experimental and control groups. Little correlation was documented among the five different adherence measures, and there was minimal correlation with clinical markers. DISCUSSION: It is unclear why the tailored adherence intervention was not efficacious in improving medication adherence. The findings suggest that these measures of medication adherence did not perform as expected and that, perhaps, they are not adequate measures of adherence. Effective and efficient adherence interventions are needed to address the barriers to medication adherence in HIV/AIDS.

Adult↗

PubMed1986

Cell surface characteristics of coagulase-negative staphylococci and their adherence to fluorinated poly(ethylenepropylene).

The ability of 21 nonencapsulated and 15 encapsulated coagulase-negative staphylococci (CNS) to adhere to xylene in xylene-water emulsions and to fluorinated poly(ethylenepropylene) (FEP) films revealed remarkable differences. Nonencapsulated CNS strains adhered well to FEP, whereas their adherence to xylene ranged widely. Encapsulated strains with low adherence to xylene showed slight adherence to FEP. Encapsulated strains which adhered well to xylene ranged widely in their adherence to FEP. It was concluded that results obtained from the xylene adherence test were not predictive of the adherence of CNS to the hydrophobic FEP surface. The number of nonwashed, slime-producing CNS strains adhering to FEP was similar to that of washed bacteria of the same strains. Bacterial adherence to FEP was decreased when FEP films were exposed to a solution containing extracellular products (EP) obtained from a slime-producing CNS strain. Bacterial adherence to xylene also decreased when the bacterial suspensions contained EP. Apparently, initial adherence of CNS to FEP and xylene is hampered by EP. Nonencapsulated and encapsulated CNS pretreated with proteolytic enzymes failed to adhere to xylene and FEP, indicating that intact surface proteins or constituents associated with surface proteins mediated their adherence to xylene and FEP. Freeze-etch replicas of a CNS strain adhering to FEP showed a smooth, flattened area on the bacterial surface at the contact site of the bacteria with the FEP, indicating that an external layer was present at the bacterial surface.

Adhesiveness↗

PubMed1985

Thrombin stimulates the adherence of neutrophils to human endothelial cells in vitro.

Highly purified human thrombin stimulates the adherence of polymorphonuclear leukocytes (PMNs) to vascular endothelial cells (EC). When Indium-labeled PMNs were incubated with primary monolayers of cultured human umbilical vein EC, the basal adherence was 10 +/- 1% of the PMNs at 5 min. Addition of thrombin (2 U/ml) increased the mean adherence to 42 +/- 15%. Enhanced neutrophil adherence in response to thrombin was confirmed by experiments with unlabeled leukocytes, examined by phase contrast and scanning electron microscopy. The action of thrombin was on the EC, since it did not directly stimulate PMN adhesiveness when measured by aggregation or by adherence to nylon fiber columns. Furthermore, enhanced neutrophil adherence occurred when endothelial monolayers were treated with thrombin and washed before adding 111Indium (111In)-labeled PMNs. Thrombin that had been inactivated with antithrombin III and heparin did not enhance neutrophil adherence. Prothrombin, Factor Xa, and fibrinogen were also ineffective. The stimulated adherence of PMNs was maximal 5 min after incubation of the EC with thrombin, and decreased thereafter. The response was dose-dependent, with half-maximal stimulation at 0.2-0.25 U thrombin/ml. The enhanced PMN adherence caused by thrombin may result in part from the production of platelet-activating factor (PAF) by the stimulated EC since thrombin-stimulated EC synthesize PAF with a time course and concentration dependence that are similar to the time and concentration relationships for thrombin-stimulated PMN adherence, PAF itself promoted neutrophil adherence to the EC monolayers, and pretreatment of PMNs with PAF decreased the adherence stimulated by thrombin and PAF, but not adherence stimulated by N-formylmethionyl-leucyl-phenylalanine and C5a fragments, which indicates specific desensitization of PAF-mediated adherence. These studies demonstrate the endothelial cell-dependent stimulation of PMN adherence by thrombin, a novel mechanism of enhanced leukocyte adherence that may be important in interactions between the coagulation and inflammatory systems.

Cell Adhesion↗

PubMedDate not supplied

Placebo practice trials: the best predictor of adherence readiness for HAART among drug users?

PURPOSE: This study assessed the utility of a placebo practice trial in determining adherence readiness among drug users. METHOD: Participants with histories of drug dependency completed a 2-week practice trial that mimicked HAART (Phase 1), followed by a 2-week observation of adherence to HAART (Phase 2) for those who began antiretroviral therapy during the study period. The primary measure of adherence was electronic monitoring. RESULTS: There were 201 participants enrolled; 39% met criteria for current drug dependency. Mean adherence to the practice trial was 67%. Of the 184 Phase 1 completers, 83 (45%) initiated HAART prior to the end of the study. Mean adherence to HAART was 74%, including 33 patients (39%) with 90+% adherence. Adherence to the practice trial was correlated with antiretroviral adherence (r =.49, p <.001), and 90+% adherence to the practice trial was an accurate marker of the "adherence readiness" (ability to adhere 90+% on HAART) of 72% of the participants. In multivariate analyses, practice trial adherence was the best independent predictor of antiretroviral adherence, accounting for 19% of the explained variance; other predictors included adherence to recent clinic appointments, cognitive functioning, unstable housing, and adherence self-efficacy. CONCLUSION: These findings suggest that a brief placebo practice trial has the potential to provide clinicians and patients with an accurate screening tool for evaluating adherence readiness.

Adult↗

PubMed2004

Integrating adherence to highly active antiretroviral therapy into children's daily lives: a qualitative study.

OBJECTIVE: To acquire a deeper understanding of factors that influence adherence to highly active antiretroviral therapy (HAART) in a pediatric population. METHODS: We performed a qualitative study of adherence in children who receive HAART in a Belgian pediatric acquired immune deficiency syndrome referral center. Eleven primary caregivers were interviewed to assess their child's adherence and influencing factors. The interview guidelines were developed on the basis of an extensive literature review. Adherence to treatment was assessed using caregivers' self-report and laboratory results. Content analysis for common items was performed, and statements of adherent and less-adherent patients were compared. RESULTS: Three main factors influenced adherence. Adherent patients were found to internalize the medical information to a stronger extent than less-adherent patients. Adherent patients showed stronger motivation to stick to the medical regimen on the basis of personal cost-benefit analyses, ie, perceived benefits outweighed the costs or difficulties experienced. Adherent patients developed greater problem-solving capacities, ie, ways to deal with practical complications of medication intake. The interviews revealed a fourth, more dynamic component: knowledge, motivation, and capacities evolved in a progressive way, related to individual stages of coping with human immunodeficiency virus (HIV). CONCLUSIONS: The data suggest that coping with HIV and the process of establishing good adherence may be interrelated. Caregivers who accept the disease may be more likely to internalize the received information and thus develop a stronger motivation to fight for the child's life. Problem-solving skills sustain this adherence, and medication becomes a priority in the adherent caregivers' daily lives. On the contrary, less-adherent caregivers may be situated at less advanced stages of the coping process. Thus, tailor-made approaches adapted to the individual HIV-related coping strategies need to be developed to improve adherence in children and caregivers.

Adolescent↗

PubMed2002

Adherence to antiretroviral therapy and outcomes in HIV-infected patients enrolled in an induction/maintenance randomized trial.

OBJECTIVE: To examine the effect of adherence to therapy on early virological response, later virological failure, and occurrence of adverse events in HIV-infected patients. DESIGN: A randomized trial of 3-month induction period of zidovudine/lamivudine/indinavir followed by a maintenance phase of zidovudine/lamivudine/indinavir, zidovudine/lamivudine or zidovudine/indinavir. MAIN OUTCOMES: Adherence was assessed by pill count. In the induction phase, early virological response was defined as plasma HIV-RNA<500 copies/ml at month 2 and in the maintenance phase, virological failure was defined as plasma HIV-RNA >500 copies/ml in two consecutive specimens. RESULTS: The median adherence rate was 97% in both induction (n=366) and maintenance phase (n=237). In the maintenance phase, pairwise comparisons showed a lower adherence rate in zidovudine/lamivudine/indinavir versus zidovudine/lamivudine (P=0.03), or versus zidovudine/indinavir (P=0.05). Only 13% of patients had an adherence over the maintenance phase of 80% or lower, while 40% of patients occasionally had an adherence rate of 80% or lower during this phase. Among the 362 patients with documented HIV-RNA at month 2, 86% had an early virological response. Adherence of 80% or greater was the only variable statistically predictive to early virological response (P<0.001), while baseline CD4, baseline HIV-RNA, and adherence of 95% or greater were not associated to virological response. In the maintenance phase, adherence, baseline HIV-RNA, HIV-RNA at month 3 and treatment groups were independently predictive to time to virological failure. Analysis by randomized groups indicated that difficulty in adherence (<80%) was predictive to time to failure (P<0.001) only in both indinavir-containing regimens. Occurrence of two or more severe adverse events (grade 3 and 4) was higher in patients with poor adherence although not statistically associated (P=0.12), while no association was found with minor adverse events. CONCLUSION: Adherence rate was globally lower in patients maintaining the original triple-drug therapy compared with those receiving less intensive regimens. Adherence rate was a time-dependent variable. Adherence to antiviral regimen of 80% or greater was predictive to early virological response, and adherence rate lower than 80% or 95% was predictive to virological failure, especially in indinavir-containing regimens. Occurrence of adverse events was not clearly associated to adherence.

Adult↗

PubMed2004

Psychosocial determinants of adherence to highly active antiretroviral therapy among injection drug users in Vancouver.

BACKGROUND: Sub-optimal adherence to highly active antiretroviral therapy (HAART) among injection drug users (IDUs) is a significant concern. As such, there is an urgent need to identify psychosocial determinants of adherence that can be incorporated into interventions designed to promote optimal adherence. OBJECTIVE: To identify psychosocial determinants of adherence to HAART, as well as self-reported reasons for missing doses of HAART among HIV-infected IDUs. METHODS: We developed an eight-item adherence self-efficacy scale comprised of two sub-scales: adherence efficacy and self-regulatory efficacy. We examined correlates between adherence self-efficacy, outcome expectations, socio-demographic characteristics, drug use and risk behaviours, social support and HAART adherence among 108 HIV-infected participants in the Vancouver Injection Drug Users Study (VIDUS). Pharmacy-based adherence to HAART was obtained through a confidential record linkage to the province of British Columbia's HIV/AIDS Drug Treatment Program. Participants were defined as adherent if they picked-up 95% of their HAART prescriptions. Participants were also asked to indicate reasons for missing doses of HAART. Logistic regression was used to identify the factors independently associated with adherence to HAART. RESULTS: Seventy-one (66%) HIV-infected IDUs were less than 95% adherent. Forgetting was the most frequently cited reason (27%) for missing doses of HAART. Factors independently associated with adherence to HAART included adherence efficacy expectations [OR=1.8 (95% CI: 1.0-3.1); P=0.039] and negative outcome expectations [OR=0.8 (95% CI: 0.7-0.9); P=0.027]. CONCLUSIONS: We found low rates of adherence to HAART among IDUs. Psychological constructs derived from self-efficacy theory are highly germane to the understanding of adherence behaviour, and interventions that address these constructs should be developed and tested among HIV-infected drug users.

Adult↗

PubMed2005

Adherence to statins, beta-blockers and angiotensin-converting enzyme inhibitors following a first cardiovascular event: a retrospective cohort study.

BACKGROUND: Population studies of statin adherence are generally restricted to one to two years of follow-up and do not analyze adherence to other drugs. OBJECTIVES: To report long-term adherence rates for statins, angiotensin-converting enzyme (ACE) inhibitors and beta-blockers in patients who recently experienced a first cardiovascular event. METHODS: Linked administrative databases in the province of Saskatchewan were used in this retrospective cohort study. Eligible patients received a new statin prescription within one year of their first cardiovascular event between 1994 and 2001. Adherence to statins, beta-blockers and ACE inhibitors was assessed from the first statin prescription to a subsequent cardiovascular event. RESULTS: Of 1221 eligible patients, the proportion of patients adherent to statin medications dropped to 60.3% at one year and 48.8% at five years. The decline in the proportion of adherent patients was most notable during the first two years (100% to 53.7%). Several factors were associated with statin adherence, including age (P = 0.012), number of physician service days (P = 0.037), chronic disease score (P = 0.032), beta-blocker adherence (P < 0.001) and ACE inhibitor adherence (P < 0.001). Adherence to beta-blockers and ACE inhibitors was very similar to adherence to statin medications at each year of follow-up. CONCLUSIONS: Patients who exhibit optimal adherence over one to two years after their initial cardiovascular event generally remain adherent over subsequent years. Also, adherence to beta-blockers and ACE inhibitors is significantly associated with statin adherence in a subset of patients; however, overall adherence to all three drugs was similarly poor.

Adrenergic beta-Antagonists↗

PubMed2002

Reported adherence as a determinant of response to highly active antiretroviral therapy in children who have human immunodeficiency virus infection.

OBJECTIVE: The complexity of highly active antiretroviral therapy (HAART), with multiple medications, formulations, and dosing intervals, makes adherence challenging. Little is known about the adherence of children to HAART. The objective of this study was to identify correlates of adherence to HAART and the relationship between adherence and study outcomes in a pediatric clinical trial. METHODS: Pediatric AIDS Clinical Trials Group 377 is a phase I/II randomized trial of 4 HAART regimens in antiretroviral-experienced, clinically stable children aged 4 months to 17 years. The 4 treatment arms include various 3- or 4-drug combinations of d4T, 3TC, nevirapine, ritonavir, and nelfinavir. After informed consent was obtained, 193 children were enrolled between December 1997 and September 1998. Questionnaires were developed to collect subject- or caregiver-reported adherence to study medications and to identify problems associated with medication administration. Every 3 months, the number of doses of each medication missed during the 3 days preceding the study visit was recorded. Full adherence (FA) and non-full adherence were defined as missing no doses and missing at least 1 dose, respectively. RESULTS: Adherence data from study week 48 or the most recent study visit were available for 125 children (week 48 for 109 children). Overall, 70% of children reported FA and 30% reported non-full adherence. Adherence did not differ by treatment arm, age, or the child's knowledge of his or her human immunodeficiency virus infection status. There was a suggestion that adherence was less for white than nonwhite children (40% vs 73% FA) and did not differ between black and Hispanic children. Rates of FA were 82% for d4T, 79% for 3TC, 83% for nevirapine, 84% for ritonavir, and 68% for nelfinavir. Despite the similar rates of FA, difficulties with taking specific medications were reported most frequently for ritonavir and nelfinavir. These included poor taste, patient refusal, and scheduling problems. Adherence was associated with the virologic response: FA was seen in 92% of children with > or =2 log10 drop in viral load and in 64% with <2 log10 drop in viral load. CONCLUSION: In children, reported adherence predicts the virologic response to HAART therapy and is a useful measure of adherence. Interventions and regimens to increase adherence to HAART should result in an improved outcome.

Acquired Immunodeficiency Syndrome↗