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      Adherence to Antiretroviral Therapy (ART) in Yaoundé-Cameroon: Association with Opportunistic Infections, Depression, ART Regimen and Side Effects

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          Abstract

          Following global efforts to increase antiretroviral therapy (ART) access in Sub-Saharan Africa, ART coverage among HIV-infected Cameroonians increased from 0% in 2003 to 22% in 2014. However, the success of current HIV treatment programs depends not only on access to ART, but also on retention in care and good treatment adherence. This is necessary to achieve viral suppression, prevent virologic failure, and reduce viral transmission and HIV/AIDS-related deaths. Previous studies in Cameroon showed poor adherence, treatment interruption, and loss to follow-up among HIV+ subjects on ART, but the factors that influence ART adherence are not well known. In the current cross-sectional study, patient/self-reported questionnaires and pharmacy medication refill data were used to quantify ART adherence and determine the factors associated with increased risk of non-adherence among HIV-infected Cameroonians. We demonstrated that drug side-effects, low CD4 cell counts and higher viral loads are associated with increased risk of non-adherence, and compared to females, males were more likely to forego ART because of side effects (p<0.05). Univariate logistic regression analysis demonstrated that subjects with opportunistic infections (on antibiotics) had 2.42-times higher odds of having been non-adherent (p<0.001). Multivariable analysis controlling for ART regimen, age, gender, and education showed that subjects with opportunistic infections had 3.1-times higher odds of having been non-adherent (p<0.0003), with significantly longer periods of non-adherence, compared to subjects without opportunistic infections (p = 0.02). We further showed that compared to younger subjects (≤40 years), older subjects (>40 years) were less likely to be non-adherent (p<0.01) and had shorter non-adherent periods (p<0.0001). The presence of depression symptoms correlated with non-adherence to ART during antibiotic treatment (r = 0.53, p = 0.04), and was associated with lower CD4 cell counts (p = 0.04) and longer non-adherent periods (p = 0.04). Change in ART regimen was significantly associated with increased likelihood of non-adherence and increased duration of the non-adherence period. Addressing these underlying risk factors could improve ART adherence, retention in care and treatment outcomes for HIV/AIDS patients in Cameroon.

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          Depression and adherence to antiretroviral therapy in low-, middle- and high-income countries: a systematic review and meta-analysis.

          Olalekan A Uthman, Jessica Magidson, Steven Safren … (2014)
          We investigated the associations between depressive symptoms and adherence to antiretroviral therapy (ART) among people living with HIV (PLHIV). We searched the PubMed, EMBASE and Cochrane CENTRAL databases for studies that reported an association between depression and adherence to ART as a primary or secondary outcome. We used a random-effect model to pool the risk estimates from the individual studies. The odds ratio (OR) with their 95 % CIs were used as summary estimates. Of 2861 citations, 111 studies that recruited 42,366 PLHIV met our inclusion criteria. When reported, the rate of PLHIV with depressive symptoms ranged from 12.8 to 78 % and the proportion of PLHIV who achieved good adherence (≥ 80 %) ranged from 20 to 98 %. There were no significant differences in rate of depressive symptoms in PLHIV by country income group; however, the proportion of PLHIV who achieved good adherence was significantly higher in lower-income countries (as defined in the 2012 World Bank Country Income Groups) (pooled rate=86 %) compared to higher-income countries (pooled rate=67.5 %; p< .05). We found that the likelihood of achieving good ART adherence was 42 % lower among those with depressive symptoms compared to those without (pooled OR=0.58, 95 % CI 0.55 to 0.62). The relationship between depressive symptoms and adherence to ART was consistent across the country's income group, study design and adherence rates. We found that the magnitude of the association significantly decreases with more recent publications and increasing study sample size. The higher the prevalence of depressive symptoms of PLHIV recruited in the studies, the lower the likelihood of achieving good adherence to ART. In conclusion, the likelihood of achieving good adherence was lower among those with depressive symptoms compared to those without.
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            Predictors and correlates of adherence to combination antiretroviral therapy (ART) for chronic HIV infection: a meta-analysis

            Nienke Langebeek, Elizabeth H Gisolf, Peter Reiss … (2014)
            Background Adherence to combination antiretroviral therapy (ART) is a key predictor of the success of human immunodeficiency virus (HIV) treatment, and is potentially amenable to intervention. Insight into predictors or correlates of non-adherence to ART may help guide targets for the development of adherence-enhancing interventions. Our objective was to review evidence on predictors/correlates of adherence to ART, and to aggregate findings into quantitative estimates of their impact on adherence. Methods We searched PubMed for original English-language papers, published between 1996 and June 2014, and the reference lists of all relevant articles found. Studies reporting on predictors/correlates of adherence of adults prescribed ART for chronic HIV infection were included without restriction to adherence assessment method, study design or geographical location. Two researchers independently extracted the data from the same papers. Random effects models with inverse variance weights were used to aggregate findings into pooled effects estimates with 95% confidence intervals. The standardized mean difference (SMD) was used as the common effect size. The impact of study design features (adherence assessment method, study design, and the United Nations Human Development Index (HDI) of the country in which the study was set) was investigated using categorical mixed effects meta-regression. Results In total, 207 studies were included. The following predictors/correlates were most strongly associated with adherence: adherence self-efficacy (SMD = 0.603, P = 0.001), current substance use (SMD = −0.395, P = 0.001), concerns about ART (SMD = −0.388, P = 0.001), beliefs about the necessity/utility of ART (SMD = 0.357, P = 0.001), trust/satisfaction with the HIV care provider (SMD = 0.377, P = 0.001), depressive symptoms (SMD = −0.305, P = 0.001), stigma about HIV (SMD = −0.282, P = 0.001), and social support (SMD = 0.237, P = 0.001). Smaller but significant associations were observed for the following being prescribed a protease inhibitor-containing regimen (SMD = −0.196, P = 0.001), daily dosing frequency (SMD = −0.193, P = 0.001), financial constraints (SMD −0.187, P = 0.001) and pill burden (SMD = −0.124, P = 0.001). Higher trust/satisfaction with the HIV care provider, a lower daily dosing frequency, and fewer depressive symptoms were more strongly related with higher adherence in low and medium HDI countries than in high HDI countries. Conclusions These findings suggest that adherence-enhancing interventions should particularly target psychological factors such as self-efficacy and concerns/beliefs about the efficacy and safety of ART. Moreover, these findings suggest that simplification of regimens might have smaller but significant effects. Electronic supplementary material The online version of this article (doi:10.1186/s12916-014-0142-1) contains supplementary material, which is available to authorized users.
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              The impact of specific HIV treatment-related adverse events on adherence to antiretroviral therapy: A systematic review and meta-analysis

              Imad Al-Dakkak, Seema Patel, Eilish McCann … (2012)
              Poor adherence to antiretroviral therapies (ARTs) in human immunodeficiency virus (HIV)-infected patients increases the risk of incomplete viral suppression, development of viral resistance, progression to acquired immune deficiency syndrome and death. This study assesses the impact of specific treatment-related adverse events (AEs) on adherence to ART in the adult HIV patient population. A systematic review of studies involving adult HIV-infected patients aged ≥ 16 years that reported an odds ratio (OR) for factors affecting adherence to ART was conducted through a search of the EMBASE® and Medline® databases. Database searches were complemented with a search of titles in the bibliographies of review papers. Studies conducted in populations limited to a particular demographic characteristic or behavioural risk were excluded. To qualify for inclusion into a meta-analysis, treatment-related AEs had to be defined similarly across studies. Also, multiple ORs from the same study were included where study sub-groups were distinct. Random effects models were used to pool ORs. In total, 19 studies and 18 ART-related AEs were included in meta-analyses. Adherence to ART was significantly lower in patients with non-specific AEs than in patients who did not experience AEs [OR = 0.623; 95% confidence interval (CI): 0.465–0.834]. Patients with specific AEs such as fatigue (OR = 0.631; 95% CI: 0.433–0.918), confusion (OR = 0.349; 95% CI: 0.184–0.661), taste disturbances (OR = 0.485; 95% CI: 0.303–0.775) and nausea (OR = 0.574; 95% CI: 0.427–0.772) were significantly less likely to adhere to ART compared to patients without these AEs. Knowledge of specific treatment-related AEs may allow for targeted management of these events and a careful consideration of well-tolerated treatment regimens to improve ART adherence and clinical outcomes.
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                Author and article information

                Contributors
                Anil Kumar: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Electronic): 1932-6203
                Publication date (Electronic): 31 January 2017
                Publication date Collection: 2017
                Volume: 12
                Issue: 1
                Electronic Location Identifier: e0170893
                Affiliations
                [1 ]Department of Neurology, Yaoundé Central Hospital, Yaoundé, Cameroon
                [2 ]Faculty of Medicine and Biomedical Sciences, University of Yaoundé I, Yaoundé, Cameroon
                [3 ]HIV-Day Care Service, Yaoundé Central Hospital, Yaoundé, Cameroon
                [4 ]Department of Biostatistics, College of Public Health, University of Nebraska Medical Center, Omaha, NE, United States of America
                [5 ]Yaoundé University Teaching Hospital, Yaoundé, Cameroon
                [6 ]Department of Psychiatry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, United States of America
                [7 ]Department of Pharmacology and Experimental Neuroscience, College of Medicine, University of Nebraska Medical Center, Omaha, NE, United States of America
                University of Missouri Kansas City, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: GDK.

                • Data curation: JYF AKN GDK.

                • Formal analysis: FQ RH GDK.

                • Funding acquisition: GDK.

                • Investigation: JYF KC DMN CTT EN LK.

                • Methodology: GDK RH AKN.

                • Project administration: GDK AKN DM.

                • Resources: CK AKN GDK.

                • Software: FQ RH.

                • Supervision: GDK AKN DM.

                • Validation: GDK RH.

                • Visualization: GDK FQ.

                • Writing – original draft: GDK.

                • Writing – review & editing: GDK RH FQ.

                Article
                Publisher ID: PONE-D-16-42143
                DOI: 10.1371/journal.pone.0170893
                PMC ID: 5283684
                PubMed ID: 28141867
                SO-VID: 3d0bacb9-e133-4c20-b100-adcde71b9f05
                Copyright © © 2017 Fonsah et al
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 22 October 2016
                Date accepted : 12 January 2017
                Page count
                Figures: 0, Tables: 13, Pages: 19
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100000025, National Institute of Mental Health;
                Award ID: MH094160
                Award Recipient :
                This work was supported by NIMH R01 MH094160.
                Categories
                Subject: Research Article
                Subject: Biology and Life Sciences
                Subject: Immunology
                Subject: Vaccination and Immunization
                Subject: Antiviral Therapy
                Subject: Antiretroviral Therapy
                Subject: Medicine and Health Sciences
                Subject: Immunology
                Subject: Vaccination and Immunization
                Subject: Antiviral Therapy
                Subject: Antiretroviral Therapy
                Subject: Medicine and Health Sciences
                Subject: Public and Occupational Health
                Subject: Preventive Medicine
                Subject: Vaccination and Immunization
                Subject: Antiviral Therapy
                Subject: Antiretroviral Therapy
                Subject: Medicine and Health Sciences
                Subject: Pharmacology
                Subject: Drugs
                Subject: Antimicrobials
                Subject: Antibiotics
                Subject: Biology and Life Sciences
                Subject: Microbiology
                Subject: Microbial Control
                Subject: Antimicrobials
                Subject: Antibiotics
                Subject: Biology and Life Sciences
                Subject: Microbiology
                Subject: Virology
                Subject: Viral Transmission and Infection
                Subject: Viral Load
                Subject: Research and Analysis Methods
                Subject: Mathematical and Statistical Techniques
                Subject: Statistical Methods
                Subject: Regression Analysis
                Subject: Physical Sciences
                Subject: Mathematics
                Subject: Statistics (Mathematics)
                Subject: Statistical Methods
                Subject: Regression Analysis
                Subject: Medicine and Health Sciences
                Subject: Pharmacology
                Subject: Adverse Reactions
                Subject: Biology and Life Sciences
                Subject: Microbiology
                Subject: Medical Microbiology
                Subject: Microbial Pathogens
                Subject: Viral Pathogens
                Subject: Immunodeficiency Viruses
                Subject: HIV
                Subject: Medicine and Health Sciences
                Subject: Pathology and Laboratory Medicine
                Subject: Pathogens
                Subject: Microbial Pathogens
                Subject: Viral Pathogens
                Subject: Immunodeficiency Viruses
                Subject: HIV
                Subject: Biology and Life Sciences
                Subject: Organisms
                Subject: Viruses
                Subject: Viral Pathogens
                Subject: Immunodeficiency Viruses
                Subject: HIV
                Subject: Biology and Life Sciences
                Subject: Organisms
                Subject: Viruses
                Subject: Immunodeficiency Viruses
                Subject: HIV
                Subject: Biology and life sciences
                Subject: Organisms
                Subject: Viruses
                Subject: RNA viruses
                Subject: Retroviruses
                Subject: Lentivirus
                Subject: HIV
                Subject: Biology and Life Sciences
                Subject: Microbiology
                Subject: Medical Microbiology
                Subject: Microbial Pathogens
                Subject: Viral Pathogens
                Subject: Retroviruses
                Subject: Lentivirus
                Subject: HIV
                Subject: Medicine and Health Sciences
                Subject: Pathology and Laboratory Medicine
                Subject: Pathogens
                Subject: Microbial Pathogens
                Subject: Viral Pathogens
                Subject: Retroviruses
                Subject: Lentivirus
                Subject: HIV
                Subject: Biology and Life Sciences
                Subject: Organisms
                Subject: Viruses
                Subject: Viral Pathogens
                Subject: Retroviruses
                Subject: Lentivirus
                Subject: HIV
                Subject: People and Places
                Subject: Geographical Locations
                Subject: Africa
                Subject: Cameroon
                Subject: Medicine and Health Sciences
                Subject: Mental Health and Psychiatry
                Subject: Mood Disorders
                Subject: Depression
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