It is well acknowledged that antiretroviral therapy (ART) discontinuation hampers the progress towards achieving the UNAIDS treatment targets that aim to treat 90% of HIV diagnosed patients and achieve viral suppression for 90% of those on treatment. Nevertheless, the magnitude, trend and risk factors for ART discontinuation have not been explored extensively. We carried out a retrospective data analysis to assess prevalence, trend and risk factors for ART discontinuation among adults in Southwest Ethiopia.
12 years retrospective cohort analysis was performed with 4900 HIV-infected adult patients between 21 June 2003 and 15 March 2015 registered at the ART clinic at Jimma University Teaching Hospital. ART discontinuation could be loss to follow-up, defaulting and/or stopping medication while remaining in care. Because data for 2003 and 2015 were incomplete, the 10 years data were used to describe trends for ART discontinuation using a line graph. We used binary logistic regression to identify factors that were correlated with ART discontinuation. To handle missing data, we applied multiple imputations assuming missing at random pattern.
In total, 4900 adult patients enrolled on ART, of whom 1090 (22.3%) had discontinued, 954 (19.5%) had transferred out, 300 (6.1%) had died, 2517 (51.4%) were alive and on ART, and the remaining 39 (0.8%) had unknown outcome status. The trend of ART discontinuation showed an upward direction in the recent times and reached a peak, accounting for a magnitude of 10%, in 2004 and 2005. Being a female (AOR = 2.1, 95%CI: 1.7–2.8), having an immunological failure (AOR = 2.3, 1.9–8.2), having tuberculosis/HIV co-infection (AOR = 1.5, 1.1–2.1) and no previous history of HIV testing (AOR = 1.8, 1.4–2.9) were the risk factors for ART discontinuation.
One out of five adults had discontinued from ART, and the trend of ART discontinuation increased recently. Discontinued adults were more likely to be females, tuberculosis/HIV co-infected, with immunological failure and no history of HIV testing. Therefore, it is vital to implement effective programs such as community ART distribution and linkage-case-management to enhance ART linkage and retention.
Citation: Gesesew HA, Ward P, Woldemichael K, Mwanri L (2017) Prevalence, trend and risk factors for antiretroviral therapy discontinuation among HIV-infected adults in Ethiopia in 2003-2015. PLoS ONE 12(6): e0179533. https://doi.org/10.1371/journal.pone.0179533
Editor: Giovanni Maga, Istituto di Genetica Molecolare, ITALY
Received: March 4, 2017; Accepted: May 31, 2017; Published: June 16, 2017
Copyright: © 2017 Gesesew et al. 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.
Data Availability: All relevant data are within the paper. The SPSS data of individual patients is not permitted to be provided to other bodies, as outlined by the Ethics Committee who approved the study. However, Hailay (email@example.com) can provide an anonymized data set for researchers who need further clarification.
Funding: This study was conducted for the partial fulfillment of a PhD in Public Health at Faculty of Medicine, Nursing and Health Sciences, Flinders University. We acknowledge Australian Government Research Training Program Scholarship for supporting the PhD program. The scholarship provider had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors did not receive any specific grant for this research.
Competing interests: The authors have declared that no competing interests exist.
Abbreviations: AIDS, acquired immunodeficiency syndrome; ART, antiretroviral therapy; CD4, cluster of differentiation 4; MIs, multiple imputations; JUTH, Jimma University Teaching Hospital; HIV, Human Immunodeficiency virus; SSA, Sub-Saharan Africa; Tb, tuberculosis; UNAIDS, The Joint United Nations Program on HIV and AIDS; WHO, World Health Organization
Globally, 38.8 million people were living with human immunodeficiency virus (HIV), 2.5 million new HIV infections, and 1.2 million HIV/AIDS (acquired immunodeficiency syndrome) deaths in 2015. Sub-Saharan Africa (SSA) contributed 76% (29 million) of the total HIV-infected people, 76% (1.9 million) of the total new HIV infections, and 75% (0.9 million) of the total HIV/AIDS deaths. The advent of antiretroviral therapy (ART) in 1996 significantly reduced HIV-related deaths. The global ART coverage in 2015 was low (40.6%), with North Africa and Middle East having the lowest coverage (19%). High-income countries had the highest coverage (67%), and SSA had coverage of about 42%. In Ethiopia, there were 768,040 HIV-infected people, 39,140 new HIV infections, and 28,650 HIV/AIDS deaths in 2015. The ART coverage in Ethiopia in 2015 was moderate (52%).
Optimum clinical and public health achievements of ART requires consistent long-term adherence. Nevertheless, ART discontinuation—interruptions to ART due to loss to follow-up (LTFU), defaulting or total stoppage of the treatment—is a big challenge. Additionally, ART discontinuation (discontinuation) causes drug resistance, diminishes the immunological benefit of treatment [6, 7], and increases AIDS-related morbidity and mortality [5, 8]. Discontinuation has been recognized as an impediment for attainment of the second 90 of the Joint United Nations Program on HIV and AIDS (UNAIDS) 90-90-90 treatment targets (sustainable provision of treatment for 90% of patients diagnosed with HIV) as it affects the sustainable intake of the treatment. Furthermore, discontinuation affects the performance of the third 90 of the UNAIDS 90-90-90 that aimed at achieving 90% of the virological success of patients on ART. This is because ART interruption lowers the efficacy of the treatment and subsequently leads to diminishing the number of CD4 cells, increases the number of viral counts, and then to failing immunological or virological success. Uganda reported 84% of virological suppression due to strong retention.
The magnitude of discontinuation in 2009 and 2012 was between 9–34% in Asia[10, 11] and 13.7–57.4% in Africa[12, 13]. In Ethiopia, the prevalence of discontinuation in 2012 and 2014 was between 9.8–31.4%[14, 15]. Previous studies in Ethiopia reported that demographic, behavioral, clinical and institutional factors were reported to contribute for discontinuation [14–18]. For example, smearing positive pulmonary tuberculosis, male gender, CD4 count <200 cells/μL, ambulatory functional status, having a mental illness, having HIV-negative partner, fear of stigma and side effects were the risk factors associated with discontnuation[14–18]. However, the previous studies that assessed either the prevalence[14, 18] or factors[14, 16–23] for discontinuation were all from the northern part of the country except two[16, 19]. This was also confirmed by our meta-analysis that reported that there were inadequate researches about ART discontinuation despite the large number of discontinued patients, and all the previous studies were concentrated on the northern and western part of Ethiopia.
The two studies[16, 19] that were conducted in the west part of the nation were case control studies and assessed only factors contributing for defaulting, reflecting that the magnitude of the problem was not explored. LTFU, another major contributor for discontinuation was not assessed. Unlike the rest of Ethiopia, the Southwest region is composed of different population groups. A refugee camp located near Jimma city, which takes refugees from different east African countries, contributes a number of HIV-infected patients enrolled in the ART clinic in Jimma University Teaching Hospital (JUTH). Furthermore, Jimma is also near Gambella region (Southwest Ethiopia), a region known to have the highest prevalence rate (6.5%) of HIV in Ethiopia, and the JUTH caters for both Jimma and Gambella zones. Since the prevalence of HIV in Southwestern region is higher (6.5%) than in other parts of the nation (<2%), it is necessary to understand whether the high prevalence is associated with other than factors for discontinuation identified in similar studies in Ethiopia.
Given the above gaps, and the clinical and public health significance of discontinuation, we have assessed the prevalence, trend and risk factors for ART discontinuation among adults by using 12 years (2003–2015) ART clinic data from JUTH in southwest Ethiopia. It is imperative to comprehensively understand the magnitude of the discontinuation problem and its influential factors in order to contextualise interventions to retain HIV patients in in care and to contribute to the Nation’s second and third UNAIDS treatment targets.
Study design, setting and participants
A retrospective cohort study was performed using data from 21 June 2003 to 15 March 2015 from the ART clinic at JUTH, Jimma, Southwest Ethiopia. The details of the study setting have been described in elsewhere . The treatment protocol for Ethiopia is implemented using World Health Organization (WHO) ART treatment guideline  and National Guidelines for Comprehensive HIV Prevention, Care and Treatment: Federal Democratic Republic of Ethiopia, MoH . According to the current treatment guidelines, HIV infected adults are eligible to start ART if their CD4 cell count is ≤ 500 cells/mm3 irrespective of WHO clinical stage, their WHO clinical stage is 3 or 4 irrespective CD4 cell count, and they are pregnant, breast feeding women, sero-discordant couples or diagnosed with active tuberculosis irrespective CD4 cell count. For all HIV-infected children below 15 years of age, ART is recommended irrespective of WHO clinical stage and CD4 cell count. All HIV-infected adults aged ≥15 years enrolled in ART care in JUTH were the target population. If the recorded outcome were death, transferred out or unknown, participants would be excluded from this study.
Data source and procedures
The data were extracted from JUTH electronic medical records (EMR) system called comprehensive care center patient application database (C-PAD). This system was designed since 2007, and data registered before 2007 were copied retrospectively to the electronic record. Fig 1 presents the schematic presentation of data extraction of discontinuation among HIV-infected adults in JUTH. In total, 4900 HIV-infected adults on ART were eligible or the study in the period between 2003 and 2015, and 3607 of them were included in the analysis. Clinicians record the clinical and non-clinical characteristics of the patients on paper, and afterward, data clerks entered the data into the EMR.
This figure presents the graphical demonstration of the data extraction process.
Two data clerks perform the data entry process, and this ensures the accuracy and reliability of the data. The International Center for AIDS Care and Support (ICAP) at Colombia University has been providing expertise assistance on the data management process and has also been providing checkups on completeness of the data. Weekly patient summary generated from the EMR system helps to flag patients with conditions that seek follow-up. Records would be excluded from a complete case analysis if outcome status of the person was death, transferred out or not recorded.
Study variables and measurements
The dependent variable was discontinuation and was dichotomized as 1) alive and on ART, and 2) discontinued. Discontinuation refers to LTFU, defaulting and/or stopping medication while remaining in care. LTFU refers to patients who had been on ART treatment and had missed at least three clinical appointments but had not yet been classified as “dead” or “transferred out” (transferred). Defaulting refers to patients who had been on ART treatment and had missed less than three clinical appointments but had not yet been classified as “dead” or “transferred”. Stopping medication refers to patients who had stopped treatment due to any reason while they have remained in care. Transferred is an official transferring of patient to another ART clinic within or outside a catchment area.
The independent variables included age, sex, marital status, educational status, religion, ART adherence, cotrimoxazole adherence, clinical failure, immunological failure, treatment failure, late presentation for HIV care (LP), tuberculosis (Tb)/HIV co-infection, baseline functional status, history of HIV testing and ART shift. Educational status was categorized in to no education (could not read and write), primary (grade 1–8), and secondary and above (grades ≥9). Functional status was classified in to the following categories: i) work—able to perform usual work, ii) ambulatory—able to perform activity of daily living, and iii) bedridden—not able to perform activity of daily living. Table 1 reports the operational definitions of LP, adherence, clinical, immunological and treatment failures.
Data cleaning and exploration were performed prior to analysis. Descriptive analysis was undertaken to explore the frequency tables and proportions for categorical data; and mean, median, range and line graph for continuous data. We described ten years trends for discontinuation (data for years 2003 and 2015 were excluded since the number of months was incomplete) using a line graph. The number of alive and on ART patients was calculated by subtracting the number of patients who dead, discontinued and Transferred from the total number of patients on the cohort. We checked for multicollinearity and potential interactions, and none was found.
We used binary logistic regression to identify factors that were correlated with discontinuation. To choose the candidate variables (P<0.25 was considered) to multiple logistic regression, we applied bivariate logistic regression analysis. P-value ≤ 0.05 was considered as a cutoff value for statistical significance in the final model. To handle missing data, we performed multiple imputations (n = 5) assuming missing at random (MAR) pattern, and we reported a model with pooled imputed values. To check goodness of fit of the final model, we applied Hosmer and Lemeshow test and was found fit. To summarize the data, we reported odds ratio and 95% confidence interval. For all data analyses, we used Statistical Package for the Social Sciences (SPSS) version 22.0.
Ethical clearance was sought from Social and Behavioral Research Ethics Committee (SBREC) at Flinders University (Project number: 7086) and Institutional Review Board (IRB) of College of Health Sciences at Jimma University (Ref No: RPGC/386/2016). The data access permission was obtained from JUTH board, and the IRB waived the need for consent. No participant was involved in the study—we did simply extract anonymised data from the record.
Characteristics of study participants
Of 8172 patients enrolled in HIV care program from 21 June 2003 to 15 March 2015, 4900 HIV-infected adults had documented commencement of ART (Fig 1). Table 2 demonstrates the characteristics of HIV patients on ART. Of the total, 80.3% were aged 25–50 years, 59.8% were females, 48.7% were married, 67.4% were Christians, and 39.1% completed primary education. The median CD4 count was 156 (0–1313) cells/mm3, and 54.3% of the participants had baseline WHO clinical stage 3 or 4. A total of 1367 (27.9%) patients were deemed Tb/HIV co-infection over the whole study period. The median time on ART was 49 months, and the estimated survival time was 121.9 (120.3–123.5) months.
Prevalence and trend of ART discontinuation
In total, 1090 (22.3%) had discontinued, 954 (19.6%) had transferred out, 300 (6.2%) had died, 2517 (51.4%) were alive and on ART, and the remaining 39 (0.8%) had unknown outcome status in the period between 2003 and 2015 (Table 3). Of the 1090 adults who had discontinued from ART, 906(83.1%) adults had defaulted, 145(13.3%) adults had LTFU and 39(3.6%) adults had stopped during the 12 years study. The prevalence of discontinuation was consistently high between 2004 and 2007. In the period between 2008 and 2011, the proportion of discontinuation showed a different trend with a sharp decline from 6% in 2008 to 2% in 2009, a sharp rise from 2% in 2009 to 6% in 2010, and then falling in 2011 to 3%. In the recent times, the proportion of discontinuation is increasing. Table 3 shows the trend in discontinuation among HIV-infected adults on ART.
Risk factors for ART discontinuation
The results from the multiple logistic regression analysis found from the analysis of a complete case and multiple imputations (MIs) are reported in Table 4. Being female (AOR = 2.1, 95%CI: 1.7–2.8), having immunological failure (AOR = 2.3, 1.9–8.2), having Tb/HIV co-infection (AOR = 1.5, 1.1–2.1) and no previous history of HIV testing (AOR = 1.8, 1.4–2.9) were the risk factors for discontinuation.
Multiple imputations (MI)
We have undertaken MI to address the missing data using five imputed data sets, and we reported a model with pooled imputed values (Table 4). In estimating factors associated with discontinuation among adults, results were similar in both MI and complete case analyses except for ART adherence and history of HIV testing. ART adherence was found to be statistically significant in the MI analysis but not in the complete case analyses, and to the contrary, history of HIV testing was not found to be statistically significant in the MI analysis unlike in the complete case analyses.
The UNAIDS target has declared three new and ambitious goals by 2020 to end AIDS epidemic by 2030: diagnosing 90% of people living with HIV, providing ART for 90% of those diagnosed with HIV, and achieving viral suppression for 90% of patients receiving treatment . Nevertheless, discontinuation from treatment challenges the success of the last two goals . One in five people on ART (22.3%) had discontinued from the treatment in the current study. When compared to findings elsewhere in Ethiopia, discontinuation rate in the current study was higher than findings from the Tigray’s study  and lower than findings from the Amhara’s study . In addition, this rate was lower than findings from studies conducted in Guinea-Bissau (51.1%), Nigeria (28%), and a multi-clinic study from Republic of Congo, Cameron and Burundi (83%). The dissimilarity in measurement, access to HIV care services, and innovation, adoption and implementation of cost-effective retention strategies could be the possible reasons of differences[44, 45].
For example, HIV care services such as ART accessibility affects the discontinuation rate. The estimated ART coverage in Ethiopia (52%) is higher than from Guinea-Bissau (25%), Nigeria (29%), Republic of Congo (25%), Cameron (22%) and Burundi (38%). This could be one of the reasons why discontinuation rate in our finding is lower than those countries. Furthermore, the introduction of innovative programs such as Health Extension Workers (HEWs) and Health Development Army (HDA) to HIV care services—programs that are not implemented in Guinea-Bissau, Nigeria, Republic of Congo, Cameron and Burundi—could affect the discontinuation rates.
The trend for discontinuation was different across years. The proportion of discontinuation in the beginning year (2004) was very high (10%) because ART was not freely available. Discontinuation had also increased from 6% in 2006 to 9% in 2007. This could be because: i) ART was universally scaled up without preparations ; and ii) there was inequity and limitations in access to HIV care services, a justification corroborated by 24% of the health facilities in Ethiopia provide ART care and 59% of the health facilities in the country provide prevention of mother to child transmission services.
The trend of discontinuation had dramatically decreased from 9% in 2007 to 2% in 2009. The overall HIV care services have been improved and had a profound contribution to the reduction of discontinuation. Also, HIV was included as one of the 16 packages in a new program called health extension program (HEP)—an innovative community based health service delivery system aiming at provision of essential primary health care services—, and this program could reduce the proportion of discontinuation. Nevertheless, as of 2011, the discontinuation has been growing, because non-governmental organizations has been phasing out. To the contrary, local governments have been allocating little budget for health developments, particularly for HIV/AIDS. We should seriously heed the issue since the developmental assistance for health budgeted by local governments is expected to grow only slightly.
Hence, the magnitude of discontinuation in the current study reflects that it is a considerable number and its trend is increasing in the recent times. Programs such as community based ART distribution[9, 50], improving adherence via medication diary for care givers, home based nursing interventions and adherence clubs could increase linkage to and retention in care and further reduce discontinuation. People living with HIV should also meaningfully be involved in the continuum of care to improve retention programs. The universal test, treat and keep strategy would dramatically improve ART retention and is fundamental in cost-effective HIV care.
Compared to males, females were more likely to discontinue from ART, a similar finding to previous studies [56, 57]. Part of the reasons for this could be due to: (i) HIV related stigma which is known to be higher in females than in males, and prohibits them out from HIV care seeking [58, 59]; (ii) Lower literacy status in females than males, which is a big challenge that prevent women from optimising the benefit of HIV care , (iii) higher usage in females than males of traditional healers which hinders females from taking ART consistently , and (v) lack integration between modern and traditional medicines which has been identified as one of the key factors in for a consistent uptake of ART programs in Ethiopia . Similar to findings by Meloni and colleagues, discontinuation was higher among patients with immunological failure than their comparator. HIV-infected patients with immunological failure are susceptible to multiple opportunistic infections and do progress to the advanced stage of HIV/AIDS rapidly leading to quick deterioration of their health status[64, 65]. Poor health status can also be among significant factors that deter them from uptaking HIV care services consistently . To address ART discontinuation problem, Programs such as linkage-case-management (LCM) that focus on multiple points of HIV care to enhance retention have been suggested as a good practice.
Although it has been stated that Tb/HIV co-infection mortality and morbidity was reduced dramatically in the era of ART [68, 69], in the current study, the odds of discontinuation was higher in Tb/HIV con-infected patients than in patients with HIV infections alone. These results are consistent with findings from earlier studies [70–72]. The intimate linkage between HIV and Tb enables the progression of HIV disease to advanced stage rapidly and thereby disallowing patients from regular treatment intake [26, 73]. In addition, the double stigma related to Tb/HIV coinfection as well as the double burden of having to take multiple pills for both conditions (pill effect) could be a compounding factor for discontinuation within this cohort. Because the burden of Tb/HIV confection is a serious problem in Ethiopia and in similar settings, it is vital to implement intervention strategies that strengthen access to universal Tb/HIV co-infection care throughout the country. It is necessary for the special attention to be given to Tb/HIV co-infection because it is well known that Tb causes the highest mortality among HIV-infected patients. The lack of history of HIV testing in association with discontinuation could be linked with poor awareness of the care[7, 74], high HIV-related stigma, and feeling of wellbeing. Although the outcomes status of current study was not known, previous studies in Ethiopia and elsewhere have shown that 9% of transferred out and 40–86% of LTFU cases failed to re-engage to the care, and half of LTFU patients after tracing were found deceased [7, 23].
It is necessary to acknowledge limitations of the current study including: i) some variables such as stigma and mental illness were not assessed due to the nature of the study design—previous studies reported that stigma and mental illness affect ART discontinuation; ii) the outcome status of discontinued patients was not known, iii) findings of this study might not infer the other level of health facilities such as health centers or private hospitals; and iv) the comparison for discontinuation may not be appropriate due the dissimilarity in definition between studies.
The magnitude of discontinuation was recorded among one in five patients, and the trend has increased recently. Discontinued patients were more likely to be females, Tb/HIV co-infected, with immunological failure and no history of HIV testing. Additionally, in order to ensure the best outcomes and enhance the course of HIV care it is necessary that patients should be tracked to establish whether they have defaulted, transferred out, or died. We recommended implementing community ART distributions, strengthening adherence clubs, and adopting benchmarking programs such as linkage-case-management to enhance ART linkage and retention which have demonstrated to be effective in similar settings. Ethiopia has to subscribe into the East African International epidemiologic Databases to Evaluate AIDS (EA-IeDEA) Consortium, not only to share uniform measurements and gain research networks, but learn good practices in implementing HIV/AIDS treatment and overall care and management.
The authors acknowledge to Jimma University Teaching Hospital for providing access to the data. This study was conducted for the partial fulfillment of a PhD in Public Health at Faculty of Medicine, Nursing and Health Sciences, Flinders University. We acknowledge Australian Government Research Training Program (RTP) Scholarship for supporting the PhD program. The scholarship provider had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors did not receive any specific grant for this research.
- Conceptualization: HAG PW KW LM.
- Formal analysis: HAG.
- Investigation: HAG.
- Methodology: HAG PW KW LM.
- Writing – original draft: HAG.
- Writing – review & editing: HAG PW KW LM.
- 1. Wang H, Wolock TM, Carter A, Nguyen G, Kyu HH, Gakidou E, et al. Estimates of global, regional, and national incidence, prevalence, and mortality of HIV, 1980–2015: the Global Burden of Disease Study 2015. Lancet HIV. 2016;3(8):e361–87. Epub 2016/07/30. pmid:27470028.
- 2. Ford N, Boulle A, Egger M. Accounting for and responding to HIV-associated mortality. AIDS (London, England). 2016;30(3):521–3. Epub 2016/01/15. pmid:26765941.
- 3. WHO. Consolidated ARV guidelines: defintions of terms 2013 [cited 2016 5 december]. Available from: http://www.who.int/hiv/pub/guidelines/arv2013/intro/keyterms/en/.
- 4. Ford N, Darder M, Spelman T, Maclean E, Mills E, Boulle A. Early adherence to antiretroviral medication as a predictor of long-term HIV virological suppression: five-year follow up of an observational cohort. PloS one. 2010;5(5):e10460. Epub 2010/05/21. pmid:20485480; PubMed Central PMCID: PMCPmc2864744.
- 5. Li X, Margolick JB, Conover CS, Badri S, Riddler SA, Witt MD, et al. Interruption and discontinuation of highly active antiretroviral therapy in the multicenter AIDS cohort study. Journal of acquired immune deficiency syndromes (1999). 2005;38(3):320–8. Epub 2005/03/01. pmid:15735452.
- 6. Assefa Y, Lynen L, Wouters E, Rasschaert F, Peeters K, Van Damme W. How to improve patient retention in an antiretroviral treatment program in Ethiopia: a mixed-methods study. BMC health services research. 2014;14. pmid:WOS:000331181300002.
- 7. Assefa Y, Lynen L, Kloos H, Hill P, Rasschaert F, Hailemariam D, et al. Long-term Outcomes and Their Determinants in Patients on Antiretroviral Treatment in Ethiopia, 2005/6-2011/12: A Retrospective Cohort Study. Jaids-Journal of Acquired Immune Deficiency Syndromes. 2015;70(4):414–9. pmid:WOS:000364316300012.
- 8. Rosen S, Fox MP, Gill CJ. Patient retention in antiretroviral therapy programs in sub-Saharan Africa: a systematic review. PLoS Med. 2007;4(10):e298. Epub 2007/10/19. pmid:17941716; PubMed Central PMCID: PMCPmc2020494.
- 9. UNAIDS. 90-90-90: On the right track towards the global target. 2016.
- 10. Zhu H, Napravnik S, Eron J, Cole S, Ma Y, Wohl D, et al. Attrition among Human Immunodeficiency Virus (HIV)- Infected Patients Initiating Antiretroviral Therapy in China, 2003–2010. PloS one. 2012;7(6):e39414. pmid:22761787
- 11. Thai S, Koole O, Un P, Ros S, De Munter P, Van Damme W, et al. Five-year experience with scaling-up access to antiretroviral treatment in an HIV care programme in Cambodia. Tropical Medicine & International Health. 2009;14(9):1048–58. pmid:19573140
- 12. Makunde WH, Francis F, Mmbando BP, Kamugisha ML, Rutta AM, Mandara CI, et al. Lost to follow up and clinical outcomes of HIV adult patients on antiretroviral therapy in care and treatment centres in Tanga City, north-eastern Tanzania. Tanzania journal of health research. 2012;14(4):250–6. Epub 2012/10/01. pmid:26591722.
- 13. Schöni-Affolter F, Keiser O, Mwango A, Stringer J, Ledergerber B, Mulenga L, et al. Estimating Loss to Follow-Up in HIV-Infected Patients on Antiretroviral Therapy: The Effect of the Competing Risk of Death in Zambia and Switzerland. PloS one. 2011;6(12):e27919. pmid:22205933
- 14. Tadesse K, Fisiha H. Predictors of Loss to Follow Up of Patients Enrolled on Antiretroviral Therapy: A Retrospective Cohort Study J AIDS Clin Res. 2014;5(12).
- 15. Wubshet M, Berhane Y, Worku A, Kebede Y, Diro E. High loss to followup and early mortality create substantial reduction in patient retention at antiretroviral treatment program in north-west ethiopia. Isrn aids. 2012;2012:721720. pmid:24052883.
- 16. Asefa T, Taha M, Dejene T, Dube L. Determinants of Defaulting from Antiretroviral Therapy Treatment in Nekemte Hospital, Eastern Wollega Zone, Western Ethiopia. Public Health Research. 2013;3(5):130–5.
- 17. Dessalegn M, Tsadik M, Lemma H. Predictors of lost to follow up to antiretroviral therapy in primary public hospital of Wukro, Tigray, Ethiopia: A case control study. Journal of AIDS and HIV Research. 2015;7(1):1–9.
- 18. Berheto TM, Haile DB, Mohammed S. Predictors of Loss to follow-up in Patients Living with HIV/AIDS after Initiation of Antiretroviral Therapy. North American journal of medical sciences. 2014;6(9):453–9. Epub 2014/10/16. pmid:25317390; PubMed Central PMCID: PMCPmc4193152.
- 19. Deribe K, Hailekiros F, Biadgilign S, Amberbir A, Beyene BK. Defaulters from antiretroviral treatment in Jimma University Specialized Hospital, Southwest Ethiopia. Tropical Medicine & International Health. 2008;13(3):328–33. pmid:WOS:000254735300005.
- 20. Bucciardini R, Fragola V, Abegaz T, Lucattini S, Halifom A, Tadesse E, et al. Retention in Care of Adult HIV Patients Initiating Antiretroviral Therapy in Tigray, Ethiopia: A Prospective Observational Cohort Study. PloS one. 2015;10(9). pmid:WOS:000360688200005.
- 21. Teshome W, Belayneh M, Moges M, Mekonnen E, Endrias M, Ayele S, et al. Do loss to follow-up and death rates from ART care vary across primary health care facilities and hospitals in south Ethiopia? A retrospective follow-up study. HIV/AIDS (Auckland, NZ). 2015;7:167–74. Epub 2015/06/13. pmid:26064071; PubMed Central PMCID: PMCPmc4455856.
- 22. Melaku Z, Lamb MR, Wang C, Lulseged S, Gadisa T, Ahmed S, et al. Characteristics and outcomes of adult Ethiopian patients enrolled in HIV care and treatment: a multi-clinic observational study. BMC public health. 2015;15. pmid:WOS:000355908900001.
- 23. Wubshet M, Berhane Y, Worku A, Kebede Y. Death and seeking alternative therapy largely accounted for lost to follow-up of patients on ART in northwest Ethiopia: a community tracking survey. PLoS ONE [Electronic Resource]. 2013;8(3):e59197. pmid:23527132.
- 24. Gesesew HA, Ward P, Hajito KW, Feyissa GT, Mohammadi L, Mwanri L. Discontinuation from Antiretroviral Therapy: A Continuing Challenge among Adults in HIV Care in Ethiopia: A Systematic Review and Meta-Analysis. PloS one. 2017;12(1):e0169651. pmid:28107430
- 25. CSA, ICF. Ethiopian Demographic Health Survey 2011. Addis Ababa and Calverton: Central Statistical Agency (Ethiopia) and ICF International, 2012.
- 26. Gesesew H, Tsehaineh B, Massa D, Tesfay A, Kahsay H, Mwanri L. The role of social determinants on tuberculosis/HIV co-infection mortality in southwest Ethiopia: A retrospective cohort study. BMC Research Notes. 2016;9(1). pmid:26868489
- 27. WHO. Antiretroviral therapy for HIV infection in adults and adolescents. Geneva: WHO, 2010.
- 28. MoH. National Guidelines for Comprehensive HIV Prevention, Care and Treatment: Federal Democrtic Republic of Ethiopia, MoH. Addis Ababa: Minstry of Health, 2014.
- 29. Paul A. Multiple imputation for missing data. A cautionary tale. Sociol Methods Res. 2000;28:301–9.
- 30. Donald R. Multiple imputation for nonresponse in surveys. New York: Harvard University, 1987.
- 31. CDC. From the Centers for Disease Control and Prevention. 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. Jama. 1993;269(6):729–30. Epub 1993/02/10. pmid:8093740.
- 32. Gesesew HA, Fessehaye A T, Birtukan T A. Factors Affecting Late Presentation for HIV/AIDS Care in Southwest Ethiopia: A Case Control Study. Public Health Research. 2013;3(4):98–107.
- 33. Abaynew Y, Deribew A, Deribe K. Factors associated with late presentation to HIV/AIDS care in South Wollo ZoneEthiopia: a case-control study. AIDS Res Ther. 2011;8:8. Epub 2011/03/02. pmid:21356115; PubMed Central PMCID: PMCPmc3058009.
- 34. Gesesew H, Tsehaineh B, Massa D, Tesfay A, Kahsay H, Mwanri L. The prevalence and associated factors for delayed presentation for HIV care among tuberculosis/HIV co-infected patients in Southwest Ethiopia: a retrospective observational cohort. Infect Dis Poverty. 2016;5(1):96. Epub 2016/11/03. pmid:27802839.
- 35. Tadios Y, Davey G. Retroviral drug adherence & its correlates in Addis Ababa, Ethiopia. Ethiopian medical journal. 2006;44.
- 36. WHO. WHO definitions of clinical, immunological and virological failure for the decision to switch ART regimens: WHO; 2013 [cited 2015 September 2]. Available from: http://www.who.int/hiv/pub/guidelines/arv2013/art/WHO_CG_table_7.15.pdf.
- 37. UNAIDS. UNAIDS 90-90-90: an ambitious treatment target to help end the AIDS epidemic Geneva, Switzerland: 2014.
- 38. UNAIDS. The gap report. Geneva, Switzerland: 2014.
- 39. Hønge BL, Jespersen S, Nordentoft PB, Medina C, da Silva D, da Silva ZJ, et al. Loss to follow-up occurs at all stages in the diagnostic and follow-up period among HIV-infected patients in Guinea-Bissau: a 7-year retrospective cohort study. BMJ Open. 2013;3(10). pmid:24163204
- 40. Agbaji OO, Abah IO, Falang KD, Ebonyi AO, Musa J, Ugoagwu P, et al. Treatment Discontinuation in Adult HIV-Infected Patients on First-Line Antiretroviral Therapy in Nigeria. Curr HIV Res. 2015;13(3):184–92. Epub 2015/05/20. pmid:25986369.
- 41. Stolka K, Iriondo-Perez J, Kiumbu M, Atibu J, Azinyue I, Akam W, et al. Characteristics of antiretroviral therapy-naive patients lost-to-care in HIV clinics in Democratic Republic of Congo, Cameroon, and Burundi. AIDS care. 2016;28(7):913–8. Epub 2016/02/09. pmid:26855169.
- 42. Chalker J, Andualem T, Minzi O, Ntaganira J, Ojoo A, Waako P, et al. Monitoring adherence and defaulting for antiretroviral therapy in 5 East african countries: an urgent need for standards. Journal of the International Association of Physicians in AIDS Care (Chicago, Ill: 2002). 2008;7(4):193–9. Epub 2008/07/16. pmid:18626124.
- 43. Sidze LK, Faye A, Tetang SN, Penda I, Guemkam G, Ateba FN, et al. Different factors associated with loss to follow-up of infants born to HIV-infected or uninfected mothers: Observations from the ANRS 12140-PEDIACAM study in Cameroon. BMC public health. 2015;15(1).
- 44. Brusamento S, Ghanotakis E, Tudor Car L, van-Velthoven MH, Majeed A, Car J. Male involvement for increasing the effectiveness of prevention of mother-to-child HIV transmission (PMTCT) programmes. Cochrane Database of Systematic Reviews. 2012;(10):N.PAG-N.PAG 1p. pmid:108103706. Language: English. Entry Date: 20101029. Revision Date: 20150712. Publication Type: Journal Article.
- 45. Tudor Car L, van-Velthoven MH, Brusamento S, Elmoniry H, Car J, Majeed A, et al. Integrating prevention of mother-to-child HIV transmission (PMTCT) programmes with other health services for preventing HIV infection and improving HIV outcomes in developing countries. The Cochrane database of systematic reviews. 2011;(6):Cd008741. Epub 2011/06/17. pmid:21678382.
- 46. CDC. HIV/AIDS progress in 2014 (update): Ethiopia. Addis Ababa, Ethiopia: WHO, 2015.
- 47. MoH. Health Sector Strategic Plan (HSDP-III), Planning and Programming Department. Addis Ababa, Ethiopia: Federal Ministry of Health, 2005.
- 48. Sidibe M, Loures L, Samb B. The UNAIDS 90-90-90 target: a clear choice for ending AIDS and for sustainable health and development. Journal of the International AIDS Society. 2016;19(1):21133. Epub 2016/07/19. pmid:27424601; PubMed Central PMCID: PMCPmc4947868.
- 49. Dieleman JL, Schneider MT, Haakenstad A, Singh L, Sadat N, Birger M, et al. Development assistance for health: past trends, associations, and the future of international financial flows for health. The Lancet. 2016;387(10037):2536–44.
- 50. Barr D, Odetoyinbo M, Mworeko L, Greenberg J. The leadership of communities in HIV service delivery. AIDS (London, England). 2015;29 Suppl 2:S121–7. Epub 2015/06/24. pmid:26102622.
- 51. Wamalwa DC, Farquhar C, Obimbo EM, Selig S, Mbori-Ngacha DA, Richardson BA, et al. Medication diaries do not improve outcomes with highly active antiretroviral therapy in Kenyan children: a randomized clinical trial. Journal of the International AIDS Society. 2009;12:8. Epub 2009/06/25. pmid:19549342; PubMed Central PMCID: PMCPmc2708138.
- 52. Berrien VM, Salazar JC, Reynolds E, McKay K. Adherence to antiretroviral therapy in HIV-infected pediatric patients improves with home-based intensive nursing intervention. AIDS patient care and STDs. 2004;18(6):355–63. Epub 2004/08/06. pmid:15294086.
- 53. Luque-Fernandez MA, Cutsem G, Goemaere E. Effectiveness of patient adherence groups as a model of care for stable patients on antiretroviral therapy in Khayelitsha, Cape town, South Africa. PloS one. 2013;8. pmid:23418518
- 54. Kim YM, Kalibala S, Neema S, Lukwago J, Weiss DC. Meaningful involvement of people living with HIV/AIDS in Uganda through linkages between network groups and health facilities: an evaluation study. Psychology, health & medicine. 2012;17(2):213–22. Epub 2011/07/23. pmid:21777091.
- 55. IFRC, GNP+. A community-based service delivery model to expand HIV prevention and treatment 2015 [cited 2016 May 06]. Available from: http://www.ifrc.org/Global/Documents/Secretariat/AIDS conference/1281400-HIV-leaflet-LR.pdf.
- 56. Gwynn RC, Fawzy A, Viho I, Wu Y, Abrams EJ, Nash D. Risk factors for loss to follow-up prior to ART initiation among patients enrolling in HIV care with CD4+ cell count ≥200 cells/μL in the multi-country MTCT-Plus Initiative. BMC health services research. 2015;15(1):247. pmid:26108273
- 57. Prosperi MC, Fabbiani M, Fanti I, Zaccarelli M, Colafigli M, Mondi A, et al. Predictors of first-line antiretroviral therapy discontinuation due to drug-related adverse events in HIV-infected patients: a retrospective cohort study. BMC infectious diseases. 2012;12:296. Epub 2012/11/14. pmid:23145925; PubMed Central PMCID: PMCPmc3519703.
- 58. Paudel V, Baral KP. Women living with HIV/AIDS (WLHA), battling stigma, discrimination and denial and the role of support groups as a coping strategy: a review of literature. Reproductive Health. 2015;12:53. pmid:26032304.
- 59. Mugoya GC, Ernst K. Gender differences in HIV-related stigma in Kenya. AIDS care. 2014;26(2):206–13. Epub 2013/06/26. pmid:23795954.
- 60. Nash D, Tymejczyk O, Gadisa T, Kulkarni SG, Hoffman S, Yigzaw M, et al. Factors associated with initiation of antiretroviral therapy in the advanced stages of HIV infection in six Ethiopian HIV clinics, 2012 to 2013. Journal of the International AIDS Society. 2016;19(1):20637. Epub 2016/04/27. pmid:27113335; PubMed Central PMCID: PMCPmc4845592.
- 61. Gedif T, Hahn HJ. Epidemiology of herbal drugs use in Addis Ababa, Ethiopia. Pharmacoepidemiology and drug safety. 2002;11(7):587–91. Epub 2002/12/05. pmid:12462136.
- 62. Kebede DK, Alemayehu A, Binyam G, Yunis M. A historical overview of traditional medicine practices and policy in Ethiopia. EthiopJHealth Dev. 2006;20(2):127–34.
- 63. Meloni ST, Chang C, Chaplin B, Rawizza H, Jolayemi O, Banigbe B, et al. Time-Dependent Predictors of Loss to Follow-Up in a Large HIV Treatment Cohort in Nigeria. Open Forum Infectious Diseases. 2014;1(2):ofu055. pmid:25734125.
- 64. Egger M, May M, Chêne G, Phillips AN, Ledergerber B, Dabis F, et al. Prognosis of HIV-1-infected patients starting highly active antiretroviral therapy: a collaborative analysis of prospective studies. Lancet. 2002;360.
- 65. Gesesew H, Gebremedhin A, Demissie TD, Kerie M, Sudhakar M. The association between perceived HIV‐related stigma and presentation for HIV/AIDS care in developing countries: a systematic review protocol. JBI Database of Systematic Reviews and Implementation Reports. 2014;12(4):60–8. pmid:01938924-201412040-00007.
- 66. Kelley CF, Kitchen CM, Hunt PW, Rodriguez B, Hecht FM, Kitahata M, et al. Incomplete peripheral CD4+ cell count restoration in HIV-infected patients receiving long-term antiretroviral treatment. Clinical infectious diseases: an official publication of the Infectious Diseases Society of America. 2009;48(6):787–94. Epub 2009/02/06. pmid:19193107; PubMed Central PMCID: PMCPmc2720023.
- 67. Duncan M, Haruka M, Rachel W, Oscar E, Sarah P, Joshua G, et al. Achieving 90% Linkage to HIV Care and Treatment: 18-month Outcomes of a Peer-delivered Linkage Case Management Program in Bukoba, Tanzania. AIDS 2016; Durban, South Africa: CDC; 2016.
- 68. Edmonds A, Lusiama J, Napravnik S, Kitetele F, Van Rie A, Behets F. Anti-retroviral therapy reduces incident tuberculosis in HIV-infected children. Int J Epidemiol. 2009;38(6):1612–21. pmid:19448046.
- 69. Abuogi LL, Mwachari C, Leslie HH, Shade SB, Otieno J, Yienya N, et al. Impact of expanded antiretroviral use on incidence and prevalence of tuberculosis in children with HIV in Kenya. Int J Tuberc Lung Dis. 2013;17(10):1291–7. Epub 2013/09/13. pmid:24025380.
- 70. Bassett IV, Chetty S, Wang B, Mazibuko M, Giddy J, Lu Z, et al. Loss to follow-up and mortality among HIV-infected people co-infected with TB at ART initiation in Durban, South Africa. Journal of Acquired Immune Deficiency Syndromes. 2012;59(1):25–30. pmid:22027877
- 71. Deribe K, Hailekiros F, Biadgilign S, Amberbir A, Beyene BK. Defaulters from antiretroviral treatment in Jimma University Specialized Hospital, Southwest Ethiopia. Trop Med Int Health. 2008;13. pmid:18298607
- 72. Rachlis B, Bakoyannis G, Easterbrook P, Genberg B, Braithwaite RS, Cohen CR, et al. Facility-Level Factors Influencing Retention of Patients in HIV Care in East Africa. PloS one. 2016;11(8):e0159994. pmid:27509182.
- 73. Toossi Z. Virological and immunological impact of tuberculosis on human immunodeficiency virus type 1 disease. J Infect Dis. 2003;188(8):1146–55. Epub 2003/10/11. pmid:14551885.
- 74. Aniley AB, Tadesse Awoke A, Ejigu Gebeye Z, Assefa Andargie K. Factors Associated With Late HIV Diagnosis among Peoples Living with HIV, Northwest Ethiopia: Hospital based Unmatched Case-control Study. J HIV Retrovirus. 2016;2(1).
- 75. Takah NF, Awungafac G, Aminde LN, Ali I, Ndasi J, Njukeng P. Delayed entry into HIV care after diagnosis in two specialized care and treatment centres in Cameroon: the influence of CD4 count and WHO staging. BMC public health. 2016;16:529. Epub 2016/07/09. pmid:27390926; PubMed Central PMCID: PMCPmc4939053.
- 76. Hickey MD, Omollo D, Salmen CR, Mattah B, Blat C, Ouma GB, et al. Movement between facilities for HIV care among a mobile population in Kenya: transfer, loss to follow-up, and reengagement. AIDS care. 2016:1–8. Epub 2016/05/05. pmid:27145451.
- 77. Evangeli M, Newell ML, Richter L, McGrath N. The Association between Self-Reported Stigma and Loss-to-Follow Up in Treatment Eligible HIV Positive Adults in Rural Kwazulu-Natal, South Africa. PloS one. 2014;9(2). pmid:WOS:000331714700010.
- 78. EA-IeDEA. East African International epidemiologic Databases to Evaluate AIDS (EA-IeDEA) Consortium 2006 [cited 2016 December 1]. Available from: https://www.iedea-ea.org/joomla/.