Antiretroviral adherence and treatment outcomes among adult Ethiopian patients

The scale-up of antiretroviral therapy (ART) services has been one of the best achievements witnessed in the health sector in Ethiopia over the past decade. A total of 339,043 adults had received treatment for Human Immunodeficiency Virus (HIV)/Acquired Immunodeficiency Syndrome (AIDS) in Ethiopia as of 2014, and this number is expected to increase over the coming years. Achievement of optimal medication adherence is becoming the greatest challenge in the management of HIV/AIDS. Patients with suboptimal adherence are at high risk of progression to AIDS, emergence of resistant viral strains, limited future treatment options, and higher treatment costs. Data on barriers to, and facilitators of, adherence in Ethiopian HIV-positive patients taking ART remains inconsistent and incomplete. The available cross-sectional studies are limited in that they have only assessed limited variables at a single point in time and qualitative studies have not yet explored factors associated with medication adherence at the individual level. While one prospective study has investigated adherence to ART in Ethiopia, it was only conducted for 3 months and also did not focus on treatment-na‚àövòve patients. The objectives of the body of work contained in this thesis were to fill these gaps using a mixed-methods approach that include both prospective quantitative and qualitative studies to establish the levels of medication adherence and identify a wide range of factors that influence medication adherence. We also assessed the incidence of adverse drug reactions (ADRs) and associated risk factors in Ethiopian patients with HIV/AIDS initiated on ART. The main study was conducted in two hospitals in Northwest Ethiopia: Gondar University and Felege-Hiwot Hospitals. It began with a prospective study in which 246 adult HIV-infected patients initiated on ART were followed from the time of initiation to 12 months of therapy. Patients had appointments every month for 6 months and every 3 months thereafter in ART clinics; research pharmacists collected data in line with patients' appointment schedules in the ART clinics. In a subsequent study, 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. Questionnaires and interview guides were developed through a systematic procedure to ensure reliability, validity, and cultural appropriateness. Of 172 who completed follow-up in the prospective study, 130 (75.6%) had ‚Äöv¢‚Ä¢95% adherence at 12 months. In the multivariate analyses, a higher baseline body mass index (BMI) (Odds Ratio (OR), 1.2; 95% CI 1.0, 1.4) and use of reminder devices ( OR, 9.1; 95% CI 2.0, 41.6) were positively associated with adherence, while a higher HIV symptom and ADR distress score was an independent negative predictor of adherence (OR, 0.90; 95% CI 0.9, 1.0). Clusters of differentiated 4 (CD4) count increase was significantly higher in the adherent patients compared to non-adherent patients at 12 months (159 cells/˜í¬¿L [interquartile range (IQR), 72-324 cells/˜í¬¿L] vs. 132 cells/˜í¬¿L [IQR, 43-190 cells/˜í¬¿L]; p = 0.026). Patients who experienced a severe ADR were less likely (OR, 0.4, 95% CI 0.2, 0.9) to be adherent to ART. Logistic regression analysis indicated that taking zidovudine-containing regimens (OR, 4.2, 95% CI 2.1, 8.4) or being unemployed (OR, 2.2, 95% CI 1.1, 4.3) were independent predictors of experiencing severe ADRs. All factors that were independent predictors of adherence in our prospective study also emerged directly or indirectly as important factors influencing adherence in the qualitative study. The qualitative study identified economic constraints, perceived stigma and discrimination, fasting, religious belief, 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. In conclusion, this work rigorously evaluated barriers to, and facilitators of, adherence to ART in Ethiopian HIV-positive patients using a mixed-methods approach. It identified economic constraints such as food insecurity and severe ADRs as important barriers to adherence while use of reminder devices promote adherence. Implementation of measures to consistently monitor severe ADRs and economic constraints, and to promote use of reminder devices have the potential to improve adherence and treatment outcomes in HIV-positive patients taking ART.