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1.  Developing an adherence support intervention for patients on antiretroviral therapy in the context of the recent IDU-driven HIV/AIDS epidemic in Estonia 
AIDS care  2013;25(7):863-873.
There is limited data on and experience with interventions for antiretroviral therapy (ART) adherence support for patients on ART in Eastern Europe. We sought to identify a feasible adherence support intervention for delivery amongst HIV-positive adults receiving care in Estonia, where the HIV/AIDS epidemic has been mainly concentrated among injection drug users. Our application of intervention mapping strategies used existing literature, formative research and multidisciplinary team input to produce a brief clinic-based intervention entitled the Situated Optimal Adherence Intervention Estonia (sOAI Estonia) which uses both Next-Step Counseling and Information-Motivation-Behavioral Skills Model approach to facilitate integration of ART into the context and demands of daily life. We present the intervention development process, the resulting sOAI Estonia approach, and describe a randomized controlled trial which is underway to evaluate the intervention (results due in spring 2013).
PMCID: PMC3651786  PMID: 23391132
ART; HAART; adherence; intervention
2.  Adherence to Antiretroviral Therapy (ART) among People Living With HIV (PLHIV): a cross-sectional survey to measure in Lao PDR 
BMC Public Health  2013;13:617.
Since 2001, antiretroviral therapy (ART) for people living with HIV (PLHIV) has been available in the Lao People’s Democratic Republic (PDR). A key factor in the effectiveness of ART is good adherence to the prescribed regimen for both individual well-being and public health. Poor adherence can contribute to the emergence of drug resistant strains of the virus and transmission during risky behaviors. Increased access to ART in low-income country settings has contributed to an interest in treatment adherence in resource–poor contexts. This study aims to investigate the proportion of adherence to ART and identify possible factors related to non-adherence to ART among people living with HIV (PLHIV) in Lao PDR.
A cross-sectional study was conducted with adults living with HIV receiving free ART at Setthathirath hospital in the capital Vientiane and Savannakhet provincial hospitals from June to November 2011. Three hundred and forty six PLHIV were interviewed using an anonymous questionnaire. The estimation of the adherence rate was based on the information provided by the PLHIV about the intake of medicine during the previous three days. The statistical software Epidata 3.1 and Stata 10.1 were used for data analysis. Frequencies and distribution of each variable were calculated by conventional statistical methods. The chi square test, Mann–Whitney test and logistic regression were used for bivariate analyses. Multiple logistic regression analysis was conducted to determine the predictors of non-adherence to ART. A p-value < 0.05 was considered to indicate statistical significance.
Of a total of 346 patients, 60% reported more than 95% adherence to ART. Reasons for not taking medicine as required were being busy (97.0%), and being forgetful (62.2%). In the multivariate analysis, educational level at secondary school (OR=3.7, 95% CI:1.3-10.1, p=0.012); illicit drug use (OR=16.1, 95% CI:1.9-128.3, p=0.011); dislike exercise (OR=0.6, 95% CI:0.4-0.9, p=0.028), and forgetting to take ARV medicine during the last month (OR=2.3, 95% CI:1.4-3.7, p=0.001) were independently associated with non-adherence.
Non-adherence to ART was associated with individual factors and exposure to ART. Priority measures to increase adherence to ART should aim to intensify counseling and comprehensive interventions, such as guidance for PLHIV on medication self-management skills, tailoring the regimen to the PLHIV life style, and improving adherence monitoring and health care services.
PMCID: PMC3707741  PMID: 23809431
Antiretroviral therapy; Adherence; PLWHIV; Self-report; Lao PDR
3.  The Information–Motivation–Behavioral Skills Model of ART Adherence in a Deep South HIV+ Clinic Sample 
AIDS and behavior  2007;13(1):66-75.
High levels of adherence to antiretroviral therapy (ART) are critical to the management of HIV, yet many people living with HIV do not achieve these levels. There is a substantial body of literature regarding correlates of adherence to ART, and theory-based multivariate models of ART adherence are emerging. The current study assessed the determinants of adherence behavior postulated by the Information–Motivation–Behavioral Skills model of ART adherence in a sample of 149 HIV-positive patients in Mississippi. Structural equation modeling indicated that ART-related information correlated with personal and social motivation, and the two sub-areas of motivation were not intercorrelated. In this Deep South sample, being better informed, socially supported, and perceiving fewer negative consequences of adherence were independently related to stronger behavioral skills for taking medications, which in turn associated with self-reported adherence. The IMB model of ART adherence appeared to well characterize the complexities of adherence for this sample.
PMCID: PMC3018830  PMID: 17876697
Information; Motivation; Behavioral skills; ART adherence; Mississippi
4.  Anxiety and depression symptoms as risk factors for non-adherence to antiretroviral therapy in Brazil 
AIDS and behavior  2008;14(2):289-299.
Depression and anxiety are common among HIV-infected people and rank among the strongest predictors of non-adherence to antiretroviral therapy (ART). This longitudinal study aimed to assess whether symptoms of anxiety and depression are predictors of non-adherence among patients initiating ART at two public referral centers (n=293) in Belo Horizonte, Brazil. Prevalence of severe anxiety and depression symptoms before starting ART was 12.6% and 5.8%, respectively. Severe anxiety was a predictor of non-adherence to ART during follow-up period (RH=1.87; 95% CI=1.14–3.06) adjusted for low education, unemployment, alcohol use in the last month and symptoms of AIDS; while a history of injection drug use had borderline statistical significance with non-adherence. These findings suggest that using a brief screening procedure to assess anxiety and depression symptoms before initiating ART help identify individuals for interventions to improve adherence and quality of life.
PMCID: PMC2859347  PMID: 18648925
anxiety; depression; psychiatric symptoms; non-adherence; antiretroviral therapy
5.  Intentional Non-Adherence to Medications among HIV Positive Alcohol Drinkers: Prospective Study of Interactive Toxicity Beliefs 
Antiretroviral therapy (ART) adherence is key to successful treatment of HIV infection and alcohol is a known barrier to adherence. Beyond intoxication, ART adherence is impacted by beliefs that mixing alcohol and medications is toxic.
To examine prospective relationships of factors contributing to intentional medication non-adherence when drinking.
People who both receive ART and drink alcohol (N = 178) were enrolled in a 12-month prospective cohort study that monitored beliefs about the hazards of mixing ART with alcohol (interactive toxicity beliefs), alcohol consumption using electronic daily diaries, ART adherence assessed by both unannounced pill counts and self-report, and chart-abstracted HIV viral load.
Participants who reported skipping or stopping their ART when drinking (N = 90, 51 %) demonstrated significantly poorer ART adherence, were less likely to be viral suppressed, and more likely to have CD4 counts under 200/cc3. Day-level analyses showed that participants who endorsed interactive toxicity beliefs were significantly more likely to miss medications on drinking days.
Confirming earlier cross-sectional studies, the current findings from a prospective cohort show that a substantial number of people intentionally skip or stop their medications when drinking. Interventions are needed to correct alcohol-related interactive toxicity misinformation and promote adherence among alcohol drinkers.
PMCID: PMC3579979  PMID: 23065532
medication adherence; alcohol use; HIV treatment beliefs
6.  Mindfulness-Based Stress Reduction for HIV Treatment Side Effects: A Randomized Wait-List Controlled Trial 
Advances in antiretroviral therapy (ART) for HIV offer life-extending benefit; however, the side effects associated with ART use negatively impact quality of life and medication adherence among people living with HIV.
This study tested the efficacy of mindfulness-based stress reduction (MBSR) for reducing ART symptoms and bother/distress related to ART side effects. Secondary aims were to test the impact of MBSR on medication adherence and psychological functioning.
Seventy-six people living with HIV who were actively taking ART and reported distress from ART-related side effects were randomly assigned to MBSR or a wait-list control standard care condition. We measured side effects, ART adherence, perceived stress, depression, positive and negative affect, and mindfulness at three time points: baseline, three-month follow-up, and six-month follow-up. Side effects and related distress were assessed separately from other symptoms.
Compared to a wait-list control, participants in the MBSR condition experienced a reduction in the frequency of symptoms attributable to antiretroviral therapies at three months post intervention (mean difference = 0.33; 95% confidence interval [CI] = 0.01, 0.66; t(132) = 2.04, P = 0.044) and at six months post intervention (mean difference = 0.38; 95% CI = 0.05, 0.71; t(132) = 2.27, P = 0.025). MBSR participants also experienced a reduction in distress associated with those symptoms at three months post intervention (mean difference = 0.47; 95% CI = 0.003, 0.94; t(132) = 1.99, P = 0.048) compared with the wait-list control condition.
Mindfulness-based stress reduction is a promising approach for reducing HIV treatment-related side effects.
PMCID: PMC3253947  PMID: 21925831
Mindfulness-based stress reduction; HIV; antiretroviral therapy; side effects; symptoms; adherence
7.  HIV-infected individuals with co-occurring bipolar disorder evidence poor antiretroviral and psychiatric medication adherence 
AIDS and behavior  2012;16(8):2257-2266.
The contribution of bipolar disorder (BD), a prevalent serious mental illness characterized by impulsivity and mood instability, to antiretroviral (ART) and psychiatric medication adherence among HIV-infected (HIV+) individuals is unknown. We examined medication adherence among 44 HIV+/BD+ persons as compared to 33 demographically- and medically-comparable HIV+/BD− persons. Classification of adherent (≥90%) or non-adherent (<90%) based on proportion of correctly taken doses over 30 days was determined using electronic medication monitoring devices. HIV+/BD+ persons were significantly less likely to be ART adherent (47.7%) as compared to HIV+/BD− (90.9%) persons. Within the HIV+/BD+ group, mean psychiatric medication adherence was significantly worse than ART medication adherence, although there was a significant correlation between ART and psychiatric adherence levels. Importantly, 30-day ART adherence was associated with plasma virologic response among HIV+/BD+ individuals. Given the high overlap of HIV and BD, and the observed medication adherence difficulties for these persons, specialized adherence improvement interventions are needed.
PMCID: PMC3351543  PMID: 22041931
Medication Adherence; HIV/AIDS; Bipolar Disorder
8.  Factors associated with lack of antiretroviral adherence among adolescents in a reference centre in Rio de Janeiro, Brazil 
International journal of STD & AIDS  2008;19(10):685-688.
The objective of this study was to describe the adherence to antiretroviral therapy (ART) among adolescents followed-up in Rio de Janeiro. This cross-sectional study included all adolescents (aged 10–19 years) followed at Instituto de Puericultura e Pediatria Martaga~ o Gesteira and Hospital Universita’ rio Clementino Fraga Filho. Adherence was determined by self-report (number of missed ART doses in three days prior to the interview). Adherence was categorized as taking _95% of the ARTs (adherent), or ,95% (non-adherent). Variables related to demographics and treatment were evaluated and if P value _0.15, they were selected for a logistic regression analysis. One hundred and one adolescents were interviewed. The mean time on ART was 91 months and the mean adherence was 94% of this, 21 were non-adherent, and 80 adherent. The risk factors associated with non-adherence were: if the patient was not concerned about ART, odds ratio (OR) ¼ 3.47 (95% confidence interval [CI] ¼ 1.13–10.68); if they do not carry an extra dose of ART, OR ¼ 6.63 (95% CI ¼ 1.73–25.47); if a health-care worker taught them how to take ART, OR ¼ 0.27 (95% CI ¼ 0.08–0.93). Adherence among adolescents was higher than expected. Factors associated with lack of adherence were: interviewees being unaware of ARTs and lack of commitment to the treatment. Interventions involving these factors must be evaluated.
PMCID: PMC2857528  PMID: 18824621
HIV; antiretroviral; adherence; adolescent; Brazil
9.  Discrimination as a Key Mediator of the Relationship Between Posttraumatic Stress and HIV Treatment Adherence among African American Men 
Posttraumatic stress disorder (PTSD) is relatively common among people living with HIV/AIDS (PLHA) and may be associated with antiretroviral therapy (ART) adherence. We examined the relationship between PTSD symptom severity and adherence among 214 African American males. Because PLHA may experience discrimination, potentially in the form of traumatic stress (e.g., hate crimes), we also examined whether perceived discrimination (related to race, HIV status, sexual orientation) is an explanatory variable in the relationship between PTSD and adherence. Adherence, monitored electronically over 6 months, was negatively correlated with PTSD total and re-experiencing symptom severity; all 3 discrimination types were positively correlated with PTSD symptoms and negatively correlated with adherence. Each discrimination type separately mediated the relationship between PTSD and adherence; when both PTSD and discrimination were included in the model, discrimination was the sole predictor of adherence. Findings highlight the critical role that discrimination plays in adherence among African American men experiencing posttraumatic stress.
PMCID: PMC3123685  PMID: 21318411
HIV; adherence; posttraumatic stress; discrimination; mediation
10.  Factors associated with suboptimal adherence to antiretroviral therapy in Viet Nam: a cross-sectional study using audio computer-assisted self-interview (ACASI) 
BMC Infectious Diseases  2013;13:154.
Optimal adherence to antiretroviral therapy (ART) is necessary for people living with HIV/AIDS (PLHIV). There have been relatively few systematic analyses of factors that promote or inhibit adherence to antiretroviral therapy among PLHIV in Asia. This study assessed ART adherence and examined factors associated with suboptimal adherence in northern Viet Nam.
Data from 615 PLHIV on ART in two urban and three rural outpatient clinics were collected by medical record extraction and from patient interviews using audio computer-assisted self-interview (ACASI).
The prevalence of suboptimal adherence was estimated to be 24.9% via a visual analogue scale (VAS) of past-month dose-missing and 29.1% using a modified Adult AIDS Clinical Trial Group scale for on-time dose-taking in the past 4 days. Factors significantly associated with the more conservative VAS score were: depression (p < 0.001), side-effect experiences (p < 0.001), heavy alcohol use (p = 0.001), chance health locus of control (p = 0.003), low perceived quality of information from care providers (p = 0.04) and low social connectedness (p = 0.03). Illicit drug use alone was not significantly associated with suboptimal adherence, but interacted with heavy alcohol use to reduce adherence (p < 0.001).
This is the largest survey of ART adherence yet reported from Asia and the first in a developing country to use the ACASI method in this context. The evidence strongly indicates that ART services in Viet Nam should include screening and treatment for depression, linkage with alcohol and/or drug dependence treatment, and counselling to address the belief that chance or luck determines health outcomes.
PMCID: PMC3614484  PMID: 23537416
ACASI; Adherence; Antiretroviral therapy; Depression; Substance use; Viet Nam
11.  Correlates of Adherence among Rural Indian Women Living with HIV/AIDS 
Journal of HIV/AIDS & social services  2012;11(4):10.1080/15381501.2012.735164.
In this prospective, randomized clinical trial, correlates of adherence to antiretroviral therapy (ART) were assessed using a baseline questionnaire among 68 rural women living with AIDS (WLA) in India. Unadjusted analyses revealed positive relationships of ART adherence with Hindu religion, and support from spouses and parents, whereas negative associations were found with depression, poor quality of life, and having ten or more HIV symptoms. Multiple linear regression analysis also revealed that WLA who were Hindu, not depressed, had ART support from spouses and parents, and perceived some benefit from ART were more adherent to ART than their respective counterparts. This study reveals the unique challenges which rural WLA experience and the need to mitigate these challenges early in ART treatment. Further, the findings enable the refinement of an intervention program which will focus on strengthening ART adherence among rural WLA.
PMCID: PMC3655775  PMID: 23687468
Adherence to ART; rural women living with AIDS in India; depression; social support
12.  Factors associated with non-adherence to highly active antiretroviral therapy in Nairobi, Kenya 
Antiretroviral therapy (ART) requires high-level (> 95%) adherence. Kenya is rolling out ART access programmes and, issue of adherence to therapy is therefore imperative. However, published data on adherence to ART in Kenya is limited. This study assessed adherence to ART and identified factors responsible for non adherence in Nairobi.
This is a multiple facility-based cross-sectional study, where 416 patients aged over 18 years were systematically selected and interviewed using a structured questionnaire about their experience taking ART. Additional data was extracted from hospital records. Patients were grouped into adherent and non-adherent based on a composite score derived from a three questions adherence tool developed by Center for Adherence Support Evaluation (CASE). Multivariate regression model was used to determine predictors of non-adherence.
Overall, 403 patients responded; 35% males and 65% females, 18% were non-adherent, and main (38%) reason for missing therapy were being busy and forgetting. Accessing ART in a clinic within walking distance from home (OR = 2.387, CI.95 = 1.155-4.931; p = 0.019) and difficulty with dosing schedule (OR = 2.310, CI.95 = 1.211-4.408, p = 0.011) predicted non-adherence.
The study found better adherence to HAART in Nairobi compared to previous studies in Kenya. However, this can be improved further by employing fitting strategies to improve patients' ability to fit therapy in own lifestyle and cue-dose training to impact forgetfulness. Further work to determine why patients accessing therapy from ARV clinics within walking distance from their residence did not adhere is recommended.
PMCID: PMC3247823  PMID: 22141425
13.  Influence of Alcohol Consumption on Adherence to and Toxicity of Antiretroviral Therapy and Survival 
Alcohol Research & Health  2010;33(3):280-287.
Antiretroviral therapy (ART) has substantially altered the fate of HIV-infected people, transforming the infection from an invariably fatal disease to a chronic condition manageable by pharmacotherapy. However, in order for ART to be effective, patients must adhere strictly to an often-demanding treatment regimen. Alcohol consumption may impact survival of HIV-infected patients through a variety of pathways. Some of these are not related to the effectiveness of ART (e.g., alcohol-induced immunosuppression that exacerbates the HIV-related immunosuppression, increased hepatotoxicity, and increased mortality from non–HIV-related causes). However, some pathways mediating alcohol’s negative effect on survival are related to ART effectiveness. In particular, alcohol consumption may reduce adherence to ART, leading to decreased ART effectiveness and, ultimately, increased HIV-related mortality. Both clinical data and computer simulations have yielded information about the impact of alcohol consumption on medication adherence in both HIV-infected and noninfected patients. The findings suggest that alcohol-related nonadherence may account for a substantial amount of preventable mortality among HIV-infected patients. These findings may have clinical implications with respect to optimal treatment for HIV-infected patients who also consume alcohol.
PMCID: PMC3860503  PMID: 23584069
Alcohol consumption; human immunodeficiency virus (HIV); HIV treatment; antiretroviral therapy; medication adherence; immunosuppression
14.  Reasons Why High Religiosity Can Co-exist with and Precipitate Discontinuation of Anti-retroviral Therapy among Different HIV Clients in Uganda: An Exploratory Study 
Religions  2012;3:817-832.
In-depth interviews were conducted with 39 very religious people living with HIV (16 had ever and 23 had never discontinued antiretroviral therapy—ART) to assess the role of religion in these treatment decisions and in coping with HIV. Participants who had ever discontinued ART gave reasons such as: teachings and prophecies from religious leaders, and supporting Biblical scriptures all of which led them to feel that God and their faith, not ART, would help them; and testimonies by their “already healed” peers who had stopped ART. Participants who had never discontinued ART gave reasons such as continuous adherence counseling from multiple sources, improvement in physical health as a result of ART, and beliefs that God heals in different ways and that non-adherence is equal to putting God to a test. High religiosity was reported to help participants cope with HIV through engagement in personal and or community protective behaviours, “taking care of other illness”, and reducing worries. When high religiosity among people living with HIV (PHAs) becomes a barrier to ART adherence, the adherence counseling provided can draw on experiences of PHAs with high religiosity who have sustained good adherence to ART and achieved good health outcomes.
PMCID: PMC3890424  PMID: 24432189
religiosity; ART adherence; Uganda
15.  Multiple Measures Reveal Antiretroviral Adherence Successes and Challenges in HIV-Infected Ugandan Children 
PLoS ONE  2012;7(5):e36737.
Adherence to HIV antiretroviral therapy (ART) among children in developing settings is poorly understood.
Methodology/Principal Findings
To understand the level, distribution, and correlates of ART adherence behavior, we prospectively determined monthly ART adherence through multiple measures and six-monthly HIV RNA levels among 121 Ugandan children aged 2–10 years for one year. Median adherence levels were 100% by three-day recall, 97.4% by 30-day visual analog scale, 97.3% by unannounced pill count/liquid formulation weights, and 96.3% by medication event monitors (MEMS). Interruptions in MEMS adherence of ≥48 hours were seen in 57.0% of children; 36.3% had detectable HIV RNA at one year. Only MEMS correlated significantly with HIV RNA levels (r = −0.25, p = 0.04). Multivariable regression found the following to be associated with <90% MEMS adherence: hospitalization of child (adjusted odds ratio [AOR] 3.0, 95% confidence interval [CI] 1.6–5.5; p = 0.001), liquid formulation use (AOR 1.4, 95%CI 1.0–2.0; p = 0.04), and caregiver’s alcohol use (AOR 3.1, 95%CI 1.8–5.2; p<0.0001). Child’s use of co-trimoxazole (AOR 0.5, 95%CI 0.4–0.9; p = 0.009), caregiver’s use of ART (AOR 0.6, 95%CI 0.4–0.9; p = 0.03), possible caregiver depression (AOR 0.6, 95%CI 0.4–0.8; p = 0.001), and caregiver feeling ashamed of child’s HIV status (AOR 0.5, 95%CI 0.3–0.6; p<0.0001) were protective against <90% MEMS adherence. Change in drug manufacturer (AOR 4.1, 95%CI 1.5–11.5; p = 0.009) and caregiver’s alcohol use (AOR 5.5, 95%CI 2.8–10.7; p<0.0001) were associated with ≥48-hour interruptions by MEMS, while second-line ART (AOR 0.3, 95%CI 0.1–0.99; p = 0.049) and increasing assets (AOR 0.7, 95%CI 0.6–0.9; p = 0.0007) were protective against these interruptions.
Adherence success depends on a well-established medication taking routine, including caregiver support and adequate education on medication changes. Caregiver-reported depression and shame may reflect fear of poor outcomes, functioning as motivation for the child to adhere. Further research is needed to better understand and build on these key influential factors for adherence intervention development.
PMCID: PMC3348916  PMID: 22590600
16.  Factors Affecting Adherence to Antiretroviral Treatment in Harari National Regional State, Eastern Ethiopia 
ISRN AIDS  2013;2013:960954.
Background. The efficacy of antiretroviral treatment (ART) depends on strict adherence to the regimen, but many factors have been identified for nonadherence. Method. To identify the factors for non-adherence to ART, a cross-sectional study was conducted on people living with human immunodeficiency virus (HIV) and attending the ART service at Hiwot Fana and Jugal hospitals; it was done from October to December, 2010. Adherence was defined as taking 95% of the prescribed doses in the week before the survey. Data were collected using a standard interview questionnaire and were analyzed using SPSS Version 16. Result. Among the 239 study participants, the magnitude of adherence to ART in the week before interview was 87%. The main reasons for nonadherence were forgetting (47.2%), traveling (18.9%), and being busy doing other things (15.1%). There was not any independent predicator identified for adherence to ART. Conclusion. Compared to other similar studies in Ethiopia, in this study a high adherence rate was found. Forgetfulness was the most common reason for the nonadherence. Therefore, the ART counseling needs to give emphasis to using memory aids. In addition, a further study on adherence rate and its determinants with multiple adherence measurements is recommended.
PMCID: PMC3773384  PMID: 24052892
17.  Adherence to antiretroviral therapy in a context of universal access, in Rio de Janeiro, Brazil 
AIDS care  2007;19(6):740-748.
Adherence is integral to improving and maintaining the health and quality of life of people living with HIV. Two-hundred HIV-positive adults recruited from teaching hospitals and non-governmental organizations (NGOs) in Rio de Janeiro City were assessed on socio-demographic factors, adherence to antiretroviral therapy (ART) and psychosocial factors hypothesized to be associated with ART. Predictors of non-adherence were analyzed using bivariate and multivariate analyses. Self-reported medication adherence was high (82% had adherence > 90%). Non-adherence was associated with personal factors (i.e. sexual orientation, self-efficacy), physical factors (i.e. loss of appetite) and interpersonal factors (i.e. doctor-patient relationship). Adherence in Brazil is as good, if not better, than that seen in the US and western Europe, which is noteworthy since the sample was derived predominantly from public healthcare settings. It is possible that the connection to NGOs in Rio de Janeiro City played a helpful role in achieving high levels of adherence in this sample of people living with HIV and AIDS. Recommendations, based on study findings, include enhancing and sustaining supportive services for NGOs, promoting patient self-efficacy and behavioral skills for adherence, increasing social network support and having healthcare providers directly address patients’ medication beliefs, attitudes and experience with side effects.
PMCID: PMC3539169  PMID: 17573593
18.  Determination of Optimized Multidisciplinary Care Team for Maximal Antiretroviral Therapy Adherence 
We seek to determine the optimized multidisciplinary care team (MDCT) composition for antiretroviral therapy (ART) adherence.
We analyzed all new regimen starts (n=10,801; 7,071 ART naïve, 3,730 ART experienced) among HIV+ patients in Kaiser Permanente California from 1996–2006. We measured 12-month adherence to ART (pharmacy refill methodology) and medical center-specific patient exposure to HIV/ID specialist (reference group), non-HIV primary care provider (PC), clinical pharmacist, nurse case manager, non-nurse care coordinator, dietician, social worker/benefits coordinator, health educator, and mental health. We used recursive partitioning to ascertain potential MDCT compositions associated with maximal mean ART adherence. We then employed mixed linear regression with clustering by provider and medical center (adjusting for ART experience, age, gender, race/ethnicity, HIV risk, HCV+, ART regimen class and calendar year) to test which potential MDCT identified had statistically significant association with ART adherence.
We found maximal increase in adherence with pharmacist +coordinator +PC (+8.1% ART adherence difference compared to reference; 95%CI: +2.7–+13.5%). Other MDCT teams with significant (p<0.05) improved adherence compared to specialist only were: nurse +social work +PC (+7.5%; +5.4–+9.7%); specialist +mental health (+6.5%; +2.6–+10.4%); pharmacist +social work +PC (+5.7%; +4.1–+7.4%); pharmacist +PC (+3.3%; +0.8–+5.8%). Among these MDCTs, there were no significant differences in mean adherence, odds maximal viral control, or change CD4+ at 12 months (except pharmacist +PC).
Various MDCTs were associated with improved adherence, including ones that did not include HIV specialist but included primary care plus other health professionals. These findings have application to HIV care team design.
PMCID: PMC3360831  PMID: 22293551
Multidisciplinary Care Team; Antiretroviral Therapy Adherence; Clinical Pharmacist; Patient Centered Medical Home; HIV Specialist; Recursive Partitioning
19.  Adherence to antiretroviral drug therapy in adult patients who are HIV-positive in Northwest Ethiopia: a study protocol 
BMJ Open  2013;3(10):e003559.
Achievement of optimal medication adherence and management of antiretroviral toxicity pose great challenges among Ethiopian patients with HIV/AIDS. There is currently a lack of long-term follow-up studies that identify the barriers to, and facilitators of, adherence to antiretroviral therapy (ART) in the Ethiopian setting. Therefore, we aim to investigate the level of adherence to ART and a wide range of potential influencing factors, including adverse drug reactions occurring with ART.
Methods and analysis
We are conducting a 1-year prospective cohort study involving adult patients with HIV/AIDS starting on ART between December 2012 and March 2013. Data are being collected on patients’ appointment dates in the ART clinics. Adherence to ART is being measured using pill count, medication possession ratio and patient's self-report. The primary outcome of the study will be the proportion of patients who are adherent to their ART regimen at 3, 6 and 12 months using pill count. Taking 95% or more of the dispensed ART regimen using pill count at given points of time will be considered the optimal level of adherence in this study. Data will be analysed using descriptive and inferential statistical procedures.
Ethics and dissemination
Ethics approval was obtained from the Tasmania Health and Medical Human Research Ethics Committee and Bahir-Dar University's Ethics Committee. The results of the study will be reported in peer-reviewed scientific journals, conferences and seminar presentations.
PMCID: PMC3816234  PMID: 24176794
Clinical Pharmacology
20.  Barriers and Facilitators of Adherence to Antiretroviral Drug Therapy and Retention in Care among Adult HIV-Positive Patients: A Qualitative Study from Ethiopia 
PLoS ONE  2014;9(5):e97353.
Antiretroviral therapy (ART) has been life saving for hundreds of thousands of Ethiopians. With increased availability of ART in recent years, achievement of optimal adherence and patient retention are becoming the greatest challenges in the management of HIV/AIDS in Ethiopia. However, few studies have explored factors influencing medication adherence to ART and retention in follow-up care among adult Ethiopian HIV-positive patients, especially in the Amhara region of the country, where almost one-third of the country’s ART is prescribed. The aim of this qualitative study was to collect such data from patients and healthcare providers in the Amhara region of Ethiopia.
Semi-structured interviews were conducted with 24 patients, of whom 11 had been lost to follow-up and were non-persistent with ART. In addition, focus group discussions were performed with 15 ART nurses and 19 case managers. All interviews and focus groups were audio-recorded, transcribed, and coded for themes and patterns in Amharic using a grounded theory approach. The emergent concepts and categories were translated into English.
Economic constraints, perceived stigma and discrimination, fasting, holy water, medication side effects, and dissatisfaction with healthcare services were major reasons for patients being non-adherent and lost to follow-up. Disclosure of HIV status, social support, use of reminder aids, responsibility for raising children, improved health on ART, and receiving education and counseling emerged as facilitators of adherence to ART.
Improving adherence and retention requires integration of enhanced treatment access with improved job and food security. Healthcare providers need to be supported to better equip patients to cope with the issues associated with ART. Development of social policies and cooperation between various agencies are required to facilitate optimal adherence to ART, patient retention, and improved patient outcomes.
PMCID: PMC4020856  PMID: 24828585
21.  The CASE adherence index: A novel method for measuring adherence to antiretroviral therapy 
AIDS care  2006;18(7):853-861.
The Center for Adherence Support Evaluation (CASE) Adherence Index, a simple composite measure of self-reported antiretroviral therapy (ART) adherence, was compared to a standard three-day self-reported adherence measure among participants in a longitudinal, prospective cross-site evaluation of 12 adherence programs throughout the United States. The CASE Adherence Index, consisting of three unique adherence questions developed for the cross-site study, along with a three-day adherence self-report were administered by interviews every three months over a one-year period. Data from the three cross-site adherence questions (individually and in combination) were compared to three-day self-report data and HIV RNA and CD4 outcomes in cross-sectional analyses. The CASE Adherence Index correlated strongly with the three-day self-reported adherence data (p < 0.001) and was more strongly associated with HIV outcomes, including a 1-log decline in HIV RNA level (maximum OR = 2.34; p < 0.05), HIV RNA<400 copies/ml (maximum OR = 2.33; p < 0.05) and performed as well as the three-day self-report when predicting CD4 count status. Participants with a CASE Index score >10 achieved a 98 cell mean increase in CD4 count over 12 months, compared to a 41 cell increase for those with scores ≤10 (p < 0.05). The CASE Adherence Index is an easy to administer instrument that provides an alternative method for assessing ART adherence in clinical settings.
PMCID: PMC2567829  PMID: 16971298
22.  Adherence to Antiretroviral Therapy and Its Effect on Survival of HIV-Infected Individuals in Jharkhand, India 
PLoS ONE  2013;8(6):e66860.
Research in India has extensively examined the factors associated with non-adherence to antiretroviral therapy (ART) with limited focus on examining the relationship between adherence to ART regimen and survival status of HIV infected patients. This study examines the effect of optimal adherence to ART on survival status of HIV infected patients attending ART centers in Jharkhand, India.
Materials and Methods
Data from a cohort of 239 HIV infected individuals who were initiated ART in 2007 were compiled from medical records retrospectively for 36 months. Socio-demographic characteristics, CD4 T cell count, presence of opportunistic infections at the time of ART initiation and ART regimen intake and survival status was collected periodically. Optimal adherence was assessed using pill count methods; patients who took <95% of the specified regimens were identified as non-adherent. Cox-proportional hazard model was used to determine the relative hazards of mortality.
More than three-fourths of the patients were male, on an average 34 year old and median CD4 T cell count was 118 cells/cmm at the time of ART registration. About 57% of the patients registered for ART were found to be adherent to ART. A total of 104 patients died in 358.5 patient-years of observation resulting in a mortality rate of 29 per 100 patient-years (95% confidence interval (CI): 23.9–35.2) and median survival time of 6.5 months (CI: 2.7–10.9). The mortality rate was higher among patients who were non-adherent to ART (64.5, CI: 50.5–82.4) than who were adherent (15.4, CI: 11.3–21.0). The risk of mortality was fourfold higher among individuals who were non-adherent to ART than who were adherent (Adjusted hazard ratio: 3.9, CI: 2.6–6.0).
Adherence to ART is associated with a higher chance of survival of HIV infected patients, ascertaining the need for interventions to improve the ART adherence and early initiation of ART.
PMCID: PMC3688964  PMID: 23825577
23.  Predictors of adherence to antiretroviral therapy among people living with HIV/AIDS in resource-limited setting of southwest ethiopia 
Good adherence to antiretroviral therapy is necessary to achieve the best virological response, lower the risk that drug resistance will develop, and reduce morbidity and mortality. Little is known about the rate and predictors of adherence in Ethiopia. Therefore this study determines the magnitude and predictors of adherence to antiretroviral therapy among people living with HIV/AIDS in Southwest Ethiopia.
A cross sectional study was carried out from January 1, 2009 to March 3, 2009 among 319 adult PLWHA (≥ 18 years) attending ART clinic at Jimma university Specialized Hospital (JUSH). Multiple Logistic regression models were constructed with adherence and independent variables to identify the predictors.
About 303(95%) of the study subjects were adherent based on self report of missed doses (dose adherence) in a one-week recall before the actual interview. The rate of self reported adherence in the study based on the combined indicator of the dose, time and food adherence measurement was 72.4%. Patients who got family support were 2 times [2.12(1.25-3.59)] more likely to adhere than those who didn't get family support as an independent predictor of overall adherence (dose, time and food). The reasons given for missing drugs were 9(27.3%) running out of medication/drug, 7(21.2%) being away from home and 7(21.2%) being busy with other things.
The adherence rate found in this study is similar to other resource limited setting and higher than the developed country. This study highlights emphasis should be given for income generating activities and social supports that helps to remember the patients for medication taking and management of opportunistic infections during the course of treatment.
PMCID: PMC2988692  PMID: 21034506
24.  Impact of HIV-related stigma on treatment adherence: systematic review and meta-synthesis 
Journal of the International AIDS Society  2013;16(3Suppl 2):18640.
Adherence to HIV antiretroviral therapy (ART) is a critical determinant of HIV-1 RNA viral suppression and health outcomes. It is generally accepted that HIV-related stigma is correlated with factors that may undermine ART adherence, but its relationship with ART adherence itself is not well established. We therefore undertook this review to systematically assess the relationship between HIV-related stigma and ART adherence.
We searched nine electronic databases for published and unpublished literature, with no language restrictions. First we screened the titles and abstracts for studies that potentially contained data on ART adherence. Then we reviewed the full text of these studies to identify articles that reported data on the relationship between ART adherence and either HIV-related stigma or serostatus disclosure. We used the method of meta-synthesis to summarize the findings from the qualitative studies.
Our search protocol yielded 14,854 initial records. After eliminating duplicates and screening the titles and abstracts, we retrieved the full text of 960 journal articles, dissertations and unpublished conference abstracts for review. We included 75 studies conducted among 26,715 HIV-positive persons living in 32 countries worldwide, with less representation of work from Eastern Europe and Central Asia. Among the 34 qualitative studies, our meta-synthesis identified five distinct third-order labels through an inductive process that we categorized as themes and organized in a conceptual model spanning intrapersonal, interpersonal and structural levels. HIV-related stigma undermined ART adherence by compromising general psychological processes, such as adaptive coping and social support. We also identified psychological processes specific to HIV-positive persons driven by predominant stigmatizing attitudes and which undermined adherence, such as internalized stigma and concealment. Adaptive coping and social support were critical determinants of participants’ ability to overcome the structural and economic barriers associated with poverty in order to successfully adhere to ART. Among the 41 quantitative studies, 24 of 33 cross-sectional studies (71%) reported a positive finding between HIV stigma and ART non-adherence, while 6 of 7 longitudinal studies (86%) reported a null finding (Pearson's χ 2=7.7; p=0.005).
We found that HIV-related stigma compromised participants’ abilities to successfully adhere to ART. Interventions to reduce stigma should target multiple levels of influence (intrapersonal, interpersonal and structural) in order to have maximum effectiveness on improving ART adherence.
PMCID: PMC3833107  PMID: 24242258
HIV; stigma; disclosure; adherence; social support; poverty
25.  HIV drug resistance surveillance in low- and middle-income countries: 2004 to 2010 
At the end of 2011, over 8 million people were receiving antiretroviral therapy (ART) in low- and middle-income countries (LMIC), a 26-fold increase from 2003. Some degree of HIV drug resistance (HIVDR) will emerge among populations on combination ART even when high levels of adherence are achieved. In 2004, the World Health Organization (WHO) initiated global HIVDR surveillance to monitor emergence and transmission of HIVDR in countries scaling-up ART.
WHO HIVDR surveillance strategy was designed to inform public health decision-making regarding choice of ART and to identify ART programme factors which could be adjusted to minimize HIVDR emergence. The strategy includes (1) surveillance of transmitted HIVDR (TDR) in recently infected populations, (2) surveillance of acquired HIVDR (ADR) in populations on ART and (3) monitoring of early warning indicators (EWI) of HIVDR which are ART programme factors favouring HIVDR emergence. Surveys used standardized protocols. Epidemiological and sequence data were quality assured.
TDR: Eighty-two surveys were conducted in 30 countries in 2004 to 2010, assessing 3588 recently infected individuals. Pooled analysis indicates an overall prevalence of 3.1% TDR to at least one drug class, 1.6% to non-nucleoside reverse transcriptase inhibitor (NNRTI), 1.3% to nucleoside reverse transcriptase inhibitor (NRTI) and 0.7% to protease inhibitor (PI). Levels of NNRTI resistance, particularly in the areas surveyed in Africa, increased over time, reaching 3.4% (95% CI=1.8 to 5.2%) in 2009. Greater ART coverage was associated, though modestly, with increased prevalence of TDR to NNRTI (P-value adjusted for region=0.039). ADR: Thirty-six ADR surveys assessing 6370 people in 12 LMIC were conducted in 2007 to 2010. HIVDR prevalence to any drug among those initiating ART ranged from 4.8% (95% CI=3.8 to 6.0%) in 2007 to 6.8% (95% CI=4.8 to 9.0%) in 2010. Ninety per cent of patients alive and on therapy at 12 months achieved viral load <1000 c/mL. Among people with virological failure, 72% had HIVDR to at least one drug. EWI: EWIs were monitored at 2017 clinics in 50 countries assessing 131,686 people since 2004. Overall, 75% of clinics met the target of 100% of patients receiving appropriate ART; 69% of clinics met the <20% target for lost to follow-up at 12 months; and only 65% of clinics provided a continuous supply of ART during a 12-month period.
Expansion of ART in LMIC has resulted in an overall increase in HIVDR, particularly to NNRTI in Africa. EWIs reveal important gaps in service delivery and programme performance. While these data call for continued and improved scale up of surveillance, they also suggest that resistance is under control in the areas surveyed, and the majority of patients initiating or switching therapy are likely to respond to currently available first- and second-line therapy.
PMCID: PMC3512549

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